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Zhang W, Ascher SB, Dolui S, Nasrallah IM, Lu Y, Neitzel J, Toledo E, Glodzik L, Shaltout HA, Hughes TM, Berry JD, Ma Y. Cardiac Biomarkers, Subclinical Brain Vascular Changes, and Cognitive Decline: Post Hoc Analysis of the SPRINT Trial. J Gerontol A Biol Sci Med Sci 2025; 80:glaf005. [PMID: 39774657 PMCID: PMC12070484 DOI: 10.1093/gerona/glaf005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND The association between subclinical cardiovascular disease (CVD) and cognitive decline in hypertensive adults and the underlying brain pathologies remain unclear. It is also undetermined whether intensifying blood pressure (BP) treatment slows down cognitive decline associated with subclinical CVD. METHODS We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial. Subclinical CVD at baseline was identified by elevated levels of high-sensitivity cardiac troponin T (hs-cTnT ≥ 14 ng/L) and N-terminal pro-B-type natriuretic peptide (NT-proBNP ≥ 125 pg/mL). Global cognitive function and domain-specific measures (memory, processing speed, language, and executive function) were assessed at baseline and follow-up (years 2, 4, and 6) in 2 733 participants. White matter lesions, cerebral blood flow, and brain tissue volume were assessed by MRI at baseline and year 4 in a subset of 639 participants. RESULTS Both elevated hs-cTnT and NT-proBNP levels at baseline were associated with accelerated cognitive decline across all domains after adjusting for potential confounding factors. The group with elevated levels of both cardiac biomarkers showed the fastest decline, with a larger annual decline rate of 0.033 (95% CI: 0.024-0.041) in the z-score of global cognitive function compared with the group with normal levels. Elevated levels of both biomarkers were also associated with a faster progression in white matter lesions, but not with changes in total brain tissue volume or cerebral blood flow. Intensive BP treatment did not attenuate these associations compared with standard treatment. CONCLUSIONS Subclinical CVD may contribute to faster white matter lesion progression and accelerated cognitive decline in patients with hypertension, regardless of intensive BP treatment.
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Affiliation(s)
- Wenxin Zhang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Simon B Ascher
- Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, California, USA
- Division of Hospital Medicine, University of California Davis, Sacramento, California, USA
| | - Sudipto Dolui
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ilya M Nasrallah
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Yuan Lu
- Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Julia Neitzel
- Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
- Department of Epidemiology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
| | - Estefania Toledo
- Department of Preventive Medicine and Public Health, University of Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Lidia Glodzik
- Department of Radiology, Brain Health Imaging Institute, Weill Cornell Medicine, New York, New York, USA
| | - Hossam A Shaltout
- Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Timothy M Hughes
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
- Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Jarett D Berry
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas, USA (Medical Sciences Section)
| | - Yuan Ma
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
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Chao HY, Lin MC, Fang TJ, Hsu MC, Liang CC, Lee MY. Quantifying Cognitive Function in Diabetes: Relationships Between AD8 Scores, HbA1c Levels, and Other Diabetic Comorbidities. Biomedicines 2025; 13:340. [PMID: 40002752 PMCID: PMC11853454 DOI: 10.3390/biomedicines13020340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/30/2025] [Accepted: 01/31/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Dementia associated with diabetes mellitus (DM) has been well documented in the literature, but studies utilizing early screening tools to target populations with mild cognitive dysfunction remain limited. This study aimed to investigate early cognitive decline by studying the relationships between "Ascertain Dementia 8" (AD8) questionnaire scores and glycemic control, lipid profiles, estimated glomerular filtration rate (eGFR), and the complications of diabetes. METHODS This case-control, cross-sectional, observational study was conducted at a medical center and an affiliated regional hospital in southern Taiwan from 30 June 2021 to 30 June 2023. Patients diagnosed with type 2 diabetes mellitus aged ≥40 years were recruited. Their past medical history, biochemical data, and AD8 score were collected at the same time. RESULTS The patients with glycated hemoglobin (HbA1c) levels of ≥7% had a higher risk of cognitive impairment than those with HbA1c levels of <7% (p < 0.001). The participants whose eGFR was <60 mL/min/1.73 m2 had a higher mean AD8 score compared to those with an eGFR of ≥60 mL/min/1.73 m2 (p = 0.008). The patients with a medical history of peripheral artery disease and diabetic neuropathy were also associated with a higher mean AD8 score (p < 0.001 and p = 0.017, respectively). CONCLUSIONS By employing the AD8 questionnaire as a sensitive screening tool, our study suggests that early cognitive decline is significantly associated with poorer glycemic control, a lower glomerular filtration rate, peripheral artery disease, and diabetic neuropathy. Early detection of these risk factors may facilitate timely interventions and tailored treatment strategies to treat or prevent cognitive dysfunction.
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Affiliation(s)
- Hsin-Yu Chao
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; (H.-Y.C.); (M.-C.L.); (T.-J.F.)
| | - Ming-Chieh Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; (H.-Y.C.); (M.-C.L.); (T.-J.F.)
| | - Tzu-Jung Fang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; (H.-Y.C.); (M.-C.L.); (T.-J.F.)
- Division of Geriatrics and Gerontology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Man-Chia Hsu
- Department of Nursing, Kaohsiung Medical University Gangshan Hospital, Kaohsiung 820111, Taiwan;
| | - Ching-Chao Liang
- Department of Laboratory Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 812015, Taiwan;
| | - Mei-Yueh Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; (H.-Y.C.); (M.-C.L.); (T.-J.F.)
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Gangshan Hospital, Kaohsiung 820111, Taiwan
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Nguyen ML, Wong D, Barson E, Staunton E, Fisher CA. Cognitive dysfunction in diabetes-related foot complications: A cohort study. J Diabetes Metab Disord 2024; 23:1017-1038. [PMID: 38932904 PMCID: PMC11196439 DOI: 10.1007/s40200-023-01381-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 12/21/2023] [Indexed: 06/28/2024]
Abstract
Objective Mild-moderate cognitive impairment has been identified in general diabetes, and early evidence indicates cognitive reductions may be more pronounced in those with diabetes-related foot complications (DRFC). Cognitive difficulties may impede treatment engagement and self-management. This requires further explication to optimise patient care and outcomes. The current study aimed to characterise cognitive function in people with DRFC using comprehensive cognitive measures. Method This cross-sectional cohort study recruited 80 adult participants (M age = 63.38, SD = 11.40, range = 30 - 89) from the Royal Melbourne Hospital Diabetic Foot Unit in Victoria, Australia, all with DRFC. Each completed a comprehensive cognitive battery (memory, attention, executive functions) and scores were calculated using age-matched population norms, where available. Results On the majority of tasks, DRFC participants performed significantly worse than age-matched norms, with the largest decrements seen in inhibition control, verbal memory, verbal abstract reasoning and working memory. Small to moderate reductions were also seen in visual learning, verbal fluency, processing speed and premorbid functioning. Demographic (lower education, male gender) and clinical factors (higher HbA1c, macrovascular and microvascular disease, longer diabetes duration) were associated with poorer cognitive functioning. Conclusions Marked reductions in cognitive functioning were found in individuals with DRFC, predominantly in the domains of verbal memory and executive functioning. Lower education, male gender and indicators of diabetes severity, such as vascular disease, are associated with heightened risk for poorer cognitive functioning. As DRFCs are a serious complication with devastating outcomes if not successfully managed, cognitive barriers to self-management must be addressed to optimise treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-023-01381-4.
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Affiliation(s)
- Mai Loan Nguyen
- School of Psychology and Public Health, La Trobe University, Bundoora, VIC 3086 Australia
| | - Dana Wong
- School of Psychology and Public Health, La Trobe University, Bundoora, VIC 3086 Australia
| | - Elizabeth Barson
- Psychosocial Oncology Program, Peter MacCallum Cancer Centre, Grattan Street, Parkville Victoria, 3052 Australia
| | - Eva Staunton
- Allied Health – Podiatry, The Royal Melbourne Hospital, Grattan Street, Parkville Victoria, 3052 Australia
| | - Caroline A. Fisher
- School of Psychology and Public Health, La Trobe University, Bundoora, VIC 3086 Australia
- Allied Health – Psychology, 4 North, The Royal Melbourne Hospital, 300 Grattan Street, Parkville Victoria, 3052 Australia
- The Melbourne Clinic, 130 Church St, Richmond Victorian, 3121 Australia
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Gunawan PY, Gunawan PA, Hariyanto TI. Risk of Dementia in Patients with Diabetes Using Sodium-Glucose Transporter 2 Inhibitors (SGLT2i): A Systematic Review, Meta-Analysis, and Meta-Regression. Diabetes Ther 2024; 15:663-675. [PMID: 38340279 PMCID: PMC10942948 DOI: 10.1007/s13300-024-01538-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 01/22/2024] [Indexed: 02/12/2024] Open
Abstract
INTRODUCTION Dementia is quite prevalent and among the leading causes of death worldwide. According to earlier research, diabetes may increase the possibility of developing dementia. However, the association between antidiabetic agents and dementia is not yet clear. This investigation examines the association between the use of sodium-glucose transporter 2 inhibitors (SGLT2i) and the risk of dementia in patients with diabetes. METHODS Up to April 18, 2023, four databases-Europe PMC, Medline, Scopus, and Cochrane Library-were searched for relevant literature. We included all studies that examine dementia risk in adults with diabetes who use SGLT2i. Random-effect models were used to compute the outcomes in this investigation, producing pooled odds ratios (OR) with 95% confidence intervals (CI). RESULTS Pooled data from seven observational studies revealed that SGLT2i use was linked to a lower risk of dementia in people with diabetes (OR 0.45, 95% CI 0.34-0.61; p < 0.00001, I2 = 97%). The reduction in the risk of dementia due to SGLT2i's neuroprotective effect was only significantly affected by dyslipidemia (p = 0.0004), but not by sample size (p = 0.2954), study duration (p = 0.0908), age (p = 0.0805), sex (p = 0.5058), hypertension (p = 0.0609), cardiovascular disease (p = 0.1619), or stroke (p = 0.2734). CONCLUSIONS According to this research, taking SGLT2i reduces the incidence of dementia in people with diabetes by having a beneficial neuroprotective impact. Randomized controlled trials (RCTs) are still required in order to verify the findings of our research.
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Affiliation(s)
- Pricilla Yani Gunawan
- Department of Neurology, Faculty of Medicine, Pelita Harapan University, Boulevard Jendral Sudirman Street, Karawaci, Tangerang, 15811, Indonesia.
| | - Paskalis Andrew Gunawan
- Division of Geriatric Medicine, Department of Internal Medicine, Faculty of Medicine, Tarumanegara University, Jakarta, 11440, Indonesia
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Li YL, Wu JJ, Li WK, Gao X, Wei D, Xue X, Hua XY, Zheng MX, Xu JG. Effects of individual metabolic brain network changes co-affected by T2DM and aging on the probabilities of T2DM: protective and risk factors. Cereb Cortex 2024; 34:bhad439. [PMID: 37991271 DOI: 10.1093/cercor/bhad439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 10/23/2023] [Accepted: 10/24/2023] [Indexed: 11/23/2023] Open
Abstract
Neuroimaging markers for risk and protective factors related to type 2 diabetes mellitus are critical for clinical prevention and intervention. In this work, the individual metabolic brain networks were constructed with Jensen-Shannon divergence for 4 groups (elderly type 2 diabetes mellitus and healthy controls, and middle-aged type 2 diabetes mellitus and healthy controls). Regional network properties were used to identify hub regions. Rich-club, feeder, and local connections were subsequently obtained, intergroup differences in connections and correlations between them and age (or fasting plasma glucose) were analyzed. Multinomial logistic regression was performed to explore effects of network changes on the probability of type 2 diabetes mellitus. The elderly had increased rich-club and feeder connections, and decreased local connection than the middle-aged among type 2 diabetes mellitus; type 2 diabetes mellitus had decreased rich-club and feeder connections than healthy controls. Protective factors including glucose metabolism in triangle part of inferior frontal gyrus, metabolic connectivity between triangle of the inferior frontal gyrus and anterior cingulate cortex, degree centrality of putamen, and risk factors including metabolic connectivities between triangle of the inferior frontal gyrus and Heschl's gyri were identified for the probability of type 2 diabetes mellitus. Metabolic interactions among critical brain regions increased in type 2 diabetes mellitus with aging. Individual metabolic network changes co-affected by type 2 diabetes mellitus and aging were identified as protective and risk factors for the likelihood of type 2 diabetes mellitus, providing guiding evidence for clinical interventions.
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Affiliation(s)
- Yu-Lin Li
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Jia-Jia Wu
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Wei-Kai Li
- School of Mathematics and Statistics, Chongqing Jiaotong University, Chongqing 400074, China
| | - Xin Gao
- Shanghai Universal Medical Imaging Diagnostic Center, Shanghai 200233, China
| | - Dong Wei
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xin Xue
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xu-Yun Hua
- Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Mou-Xiong Zheng
- Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Jian-Guang Xu
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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Miranda O, Fan P, Qi X, Wang H, Brannock MD, Kosten T, Ryan ND, Kirisci L, Wang L. Prediction of Adverse Events Risk in Patients with Comorbid Post- Traumatic Stress Disorder and Alcohol Use Disorder Using Electronic Medical Records by Deep Learning Models. RESEARCH SQUARE 2023:rs.3.rs-3299369. [PMID: 37790550 PMCID: PMC10543461 DOI: 10.21203/rs.3.rs-3299369/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/05/2023]
Abstract
Background Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic medical records (EMR) to predict suicide related event (SRE) risk in post-traumatic stress disorder (PTSD) patients. Methods We applied DeepBiomarker2 through data integration of multimodal information: lab test, medication, co-morbidities, and social determinants of health. We analyzed EMRs of 5,565 patients from University of Pittsburgh Medical Center with a diagnosis of PTSD and alcohol use disorder (AUD) on risk of developing an adverse event (opioid use disorder, SREs, depression and death). Results DeepBiomarker2 predicted whether a PTSD + AUD patient will have a diagnosis of any adverse events (SREs, opioid use disorder, depression, death) within 3 months with area under the receiver operator curve (AUROC) of 0.94. We found piroxicam, vilazodone, dronabinol, tenofovir, suvorexant, empagliflozin, famciclovir, veramyst, amantadine, sulfasalazine, and lamivudine to have potential to reduce risk. Conclusions DeepBiomarker2 can predict multiple adverse event risk with high accuracy and identify potential risk and beneficial factors. Our results offer suggestions for personalized interventions in a variety of clinical and diverse populations.
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Andreea MM, Surabhi S, Razvan-Ionut P, Lucia C, Camelia N, Emil T, Tiberiu NI. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: Harms or Unexpected Benefits? MEDICINA (KAUNAS, LITHUANIA) 2023; 59:742. [PMID: 37109700 PMCID: PMC10143699 DOI: 10.3390/medicina59040742] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/29/2023] [Accepted: 04/08/2023] [Indexed: 04/29/2023]
Abstract
There is a need for innovative pharmaceutical intervention in light of the increasing prevalence of metabolic disease and cardiovascular disease. The kidneys' sodium-glucose cotransporter 2 inhibitors (SGLT2) receptors are targeted to reduce glucose reabsorption by SGLT2. Patients with type 2 diabetes mellitus (T2DM) benefit the most from reduced blood glucose levels, although this is just one of the numerous physiological consequences. To establish existing understanding and possible advantages and risks for SGLT2 inhibitors in clinical practice, this article will explore the influence of SGLT2 inhibitors on six major organ systems. In addition, this literature review will discuss the benefits and potential drawbacks of SGLT2 inhibitors on various organ systems and their potential application in therapeutic settings.
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Affiliation(s)
- Munteanu Madalina Andreea
- Department of Cardiology, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
- “Theodor Burghele” Clinical Hospital, 050653 Bucharest, Romania
| | - Swarnkar Surabhi
- Department of Cardiovascular Science, University Medical Center Gottingen, 37075 Gottingen, Germany
| | - Popescu Razvan-Ionut
- “Theodor Burghele” Clinical Hospital, 050653 Bucharest, Romania
- Department of Urology, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
| | - Ciobotaru Lucia
- Department of Nephrology, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
| | - Nicolae Camelia
- Department of Cardiology, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
- “Theodor Burghele” Clinical Hospital, 050653 Bucharest, Romania
| | - Tufanoiu Emil
- Department of Neurology, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
- Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Nanea Ioan Tiberiu
- Department of Cardiology, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
- “Theodor Burghele” Clinical Hospital, 050653 Bucharest, Romania
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Jensen M, Zeller T, Twerenbold R, Thomalla G. Circulating cardiac biomarkers, structural brain changes, and dementia: Emerging insights and perspectives. Alzheimers Dement 2023; 19:1529-1548. [PMID: 36735636 DOI: 10.1002/alz.12926] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 12/19/2022] [Indexed: 02/04/2023]
Abstract
Diseases of the heart and brain are strongly linked to each other, and cardiac dysfunction is associated with cognitive decline and dementia. This link between cardiovascular disease and dementia offers opportunities for dementia prevention through prevention and treatment of cardiovascular risk factors and heart disease. Increasing evidence suggests the clinical utility of cardiac biomarkers as risk markers for structural brain changes and cognitive impairment. We propose the hypothesis that structural brain changes are the link between impaired cardiac function, as captured by blood-based cardiac biomarkers, and cognitive impairment. This review provides an overview of the literature and illustrates emerging insights into the association of markers of hemodynamic stress (natriuretic peptides) and markers of myocardial injury (cardiac troponins) with imaging findings of brain damage and cognitive impairment or dementia. Based on these findings, we discuss potential pathophysiological mechanisms underlying the association of cardiac biomarkers with structural brain changes and dementia. We suggest testable hypotheses and a research plan to close the gaps in understanding the mechanisms linking vascular damage and neurodegeneration, and to pave the way for targeted effective interventions for dementia prevention. From a clinical perspective, cardiac biomarkers open the window for early identification of patients at risk of dementia, who represent a target population for preventive interventions targeting modifiable cardiovascular risk factors to avert cognitive decline and dementia.
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Affiliation(s)
- Märit Jensen
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Centre for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
| | - Tanja Zeller
- German Centre for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.,University Center of Cardiovascular Science, University Heart and Vascular Center Hamburg, Clinic for Cardiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Raphael Twerenbold
- German Centre for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.,University Center of Cardiovascular Science, University Heart and Vascular Center Hamburg, Clinic for Cardiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Götz Thomalla
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Centre for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
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Ciudin A, Simó R. New methods for the diagnosis and monitoring of cognitive function in patients with type 2 diabetes. Front Endocrinol (Lausanne) 2022; 13:1024794. [PMID: 36531450 PMCID: PMC9751391 DOI: 10.3389/fendo.2022.1024794] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 11/04/2022] [Indexed: 12/02/2022] Open
Abstract
The presence of type 2 diabetes acts as an accelerator of cognitive impairment (mild cognitive impairment and later dementia), with a significant impact on the management of the disease and its complications. Therefore, it is recommended to perform an annual evaluation of cognitive function in patients with diabetes older than 65 years. Current guidelines still recommend the use of the Minimental State Evaluation Test (MMSE) as screening test, but it has a modest sensitivity and specificity for identifying mild cognitive impairment. This represents an important gap because patients with mild cognitive impairment are at risk of progressing to dementia. The neurocognitive diagnosis is based on complex neuropsychological tests, which require specifically trained personnel and are time consuming, making its routine incorporation into daily clinical practice unfeasible. Therefore, at present there are no reliable biomarkers to identify patients with type 2 diabetes at increased risk of developing cognitive impairment. Since the brain and the retina have a common embryological origin, our Research Group, has worked over the last 10 years evaluating the usefulness of the retina as a "window" to the brain. We provided evidence that retinal microperimetry is a simple, feasible and useful tool for screening and monitoring cognitive function in patients with type 2 diabetes. We propose a review of actual tests recommended for screening of cognitive impairment as well as an update of new emerging methods, such as retinal microperimetry.
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Affiliation(s)
- Andreea Ciudin
- Endocrinology and Nutrition Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Universitat Autónoma de Barcelona, Department of Human Physiology and Inmunology, Barcelona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDem), Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Simó
- Endocrinology and Nutrition Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDem), Instituto de Salud Carlos III, Madrid, Spain
- Universitat Autónoma de Barcelona, Department of Medicine, Barcelona, Spain
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Wang X, Li X, Wang W, Shi G, Wu R, Guo L, Lu C. Longitudinal Associations of Newly Diagnosed Prediabetes and Diabetes with Cognitive Function among Chinese Adults Aged 45 Years and Older. J Diabetes Res 2022; 2022:9458646. [PMID: 35936393 PMCID: PMC9352492 DOI: 10.1155/2022/9458646] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 06/21/2022] [Accepted: 07/08/2022] [Indexed: 11/24/2022] Open
Abstract
With population aging, diabetes mellitus and cognitive function decline are common health problems among older adults worldwide. This longitudinal study is aimed at estimating the longitudinal associations of newly diagnosed prediabetes and diabetes status with cognitive function among Chinese adults aged 45 years and older and evaluating the clinical risk factors associated with cognitive function. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). A total of 8716 participants meeting the inclusion criteria were enrolled between 2011 and 2012 at baseline, and 6125 participants completed the follow-up survey in 2018. Cognitive function, newly diagnosed diabetic status, depression, body mass index, and clinical and biochemical measurements were collected. At baseline, the mean age of the participants was 58.93 (SD: 9.76) years, 3987 (45.7%) were males, 1802 (20.7%) participants were newly diagnosed with prediabetes, and 935 (10.7%) were diabetes patients. After adjusting for control variables, diabetes was a significant risk factor for subsequent cognitive decline (unstandardized βestimate = -0.50, 95%CI = -0.98 ~ -0.02). Subgroup analyses found that the association of diabetes with cognitive decline was significant in females. Stratification analyses found that among prediabetes patients, triglyceride concentrations were negatively associated with cognitive function; among diabetes patients, high-sensitivity C-reactive protein was significantly associated with cognitive decline. The newly diagnosed diabetes status at baseline was associated with subsequent cognitive decline among middle-aged and elderly Chinese, especially in females. The management of triglycerides through lifestyle modification for prediabetes and specific adjunctive anti-inflammatory therapy for diabetes might benefit cognitive performance.
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Affiliation(s)
- Xiaojie Wang
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
- Department of Neurology, Shenzhen Qianhai Shekou Free Trade Zone Hospital (Shenzhen Shekou People's Hospital), Shenzhen 518067, China
| | - Xiuwen Li
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Wanxin Wang
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Guangduoji Shi
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Ruipeng Wu
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Lan Guo
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Ciyong Lu
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
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11
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Ehtewish H, Arredouani A, El-Agnaf O. Diagnostic, Prognostic, and Mechanistic Biomarkers of Diabetes Mellitus-Associated Cognitive Decline. Int J Mol Sci 2022; 23:6144. [PMID: 35682821 PMCID: PMC9181591 DOI: 10.3390/ijms23116144] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/29/2022] [Accepted: 03/29/2022] [Indexed: 01/27/2023] Open
Abstract
Cognitive dysfunctions such as mild cognitive impairment (MCI), Alzheimer's disease (AD), and other forms of dementia are recognized as common comorbidities of type 2 diabetes mellitus (T2DM). Currently, there are no disease-modifying therapies or definitive clinical diagnostic and prognostic tools for dementia, and the mechanisms underpinning the link between T2DM and cognitive dysfunction remain equivocal. Some of the suggested pathophysiological mechanisms underlying cognitive decline in diabetes patients include hyperglycemia, insulin resistance and altered insulin signaling, neuroinflammation, cerebral microvascular injury, and buildup of cerebral amyloid and tau proteins. Given the skyrocketing global rates of diabetes and neurodegenerative disorders, there is an urgent need to discover novel biomarkers relevant to the co-morbidity of both conditions to guide future diagnostic approaches. This review aims to provide a comprehensive background of the potential risk factors, the identified biomarkers of diabetes-related cognitive decrements, and the underlying processes of diabetes-associated cognitive dysfunction. Aging, poor glycemic control, hypoglycemia and hyperglycemic episodes, depression, and vascular complications are associated with increased risk of dementia. Conclusive research studies that have attempted to find specific biomarkers are limited. However, the most frequent considerations in such investigations are related to C reactive protein, tau protein, brain-derived neurotrophic factor, advanced glycation end products, glycosylated hemoglobin, and adipokines.
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Affiliation(s)
- Hanan Ehtewish
- Division of Biological and Biomedical Sciences (BBS), College of Health & Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar;
| | - Abdelilah Arredouani
- Division of Biological and Biomedical Sciences (BBS), College of Health & Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar;
- Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar
| | - Omar El-Agnaf
- Division of Biological and Biomedical Sciences (BBS), College of Health & Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar;
- Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar
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12
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Lin F, Pa J, Karim R, Hodis HN, Han SD, Henderson VW, St John JA, Mack WJ. Subclinical carotid artery atherosclerosis and cognitive function in older adults. Alzheimers Res Ther 2022; 14:63. [PMID: 35526057 PMCID: PMC9077926 DOI: 10.1186/s13195-022-00997-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 04/02/2022] [Indexed: 12/01/2022]
Abstract
Background The combined effects of increased life expectancy and the considerable number of persons reaching old age will magnify the dementia epidemic in the USA. Demonstration that subclinical atherosclerosis precedes and is associated with cognitive impairment suggests a modifiable risk factor for age-associated cognitive impairment and dementia. The purpose of this study is to determine whether subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) is associated with changes in cognitive function over time in older adults. Methods This study combined longitudinal data from three clinical trials conducted between 2000 and 2013: the B-Vitamin Atherosclerosis Intervention Trial (BVAIT), the Women’s Isoflavone Soy Health (WISH) trial, and the Early versus Late Intervention Trial with Estradiol (ELITE). Participants were recruited from the general population in the Greater Los Angeles area and were free of cardiovascular disease and diabetes; no cognitive or psychiatric exclusion criteria were specified. The same standardized protocol for ultrasound image acquisition and measurement of CIMT was used in all trials. CIMT measurements performed at baseline and 2.5 years were used in these analyses. Cognitive function was assessed at baseline and 2.5 years using a battery of 14 standardized cognitive tests. All clinical trials were conducted at the University of Southern California Atherosclerosis Research Unit, Los Angeles, and had at least 2.5 years of cognitive follow-up. Results A total of 308 men and 1187 women, mean age of 61 years, were included in the combined longitudinal dataset for the primary analysis. No associations were found between CIMT and cognitive function at baseline or at 2.5 years. There was a weak inverse association between CIMT measured at baseline and change in global cognition assessed over 2.5 years (β (SE) = − 0.056 (0.028) units per 0.1 mm CIMT, 95% CI − 0.110, − 0.001, p = 0.046). No associations between CIMT at baseline and changes in executive function, verbal memory, or visual memory were found. Conclusions In this sample of healthy older adults, our findings suggest an association between subclinical atherosclerosis and change in global cognitive function over 2.5 years. Stronger associations were observed longitudinally over 2.5 years than cross-sectionally. When analysis was stratified by age group (<65 and ≥65 years old), the inverse association remained statistically significant for participants in the older age group. Subclinical atherosclerosis of the carotid artery may be a modifiable correlate of cognitive decline in middle and older age. Trial registration BVAIT, NCT00114400. WISH, NCT00118846. ELITE, NCT00114517.
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Affiliation(s)
- Felice Lin
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Soto Street Building Suite 202Y, 2001 North Soto St, Los Angeles, CA, 90089, USA.
| | - Judy Pa
- Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA
| | - Roksana Karim
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Soto Street Building Suite 202Y, 2001 North Soto St, Los Angeles, CA, 90089, USA.,Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Howard N Hodis
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Soto Street Building Suite 202Y, 2001 North Soto St, Los Angeles, CA, 90089, USA.,Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.,Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - S Duke Han
- Department of Family Medicine, University of Southern California, Los Angeles, CA, USA.,Department of Neurology, University of Southern California, Los Angeles, CA, USA.,Department of Psychology, University of Southern California, Los Angeles, CA, USA.,School of Gerontology, University of Southern California, Los Angeles, CA, USA
| | - Victor W Henderson
- Departments of Epidemiology and Population Health and of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA
| | - Jan A St John
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Soto Street Building Suite 202Y, 2001 North Soto St, Los Angeles, CA, 90089, USA.,Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Wendy J Mack
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Soto Street Building Suite 202Y, 2001 North Soto St, Los Angeles, CA, 90089, USA.,Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.,School of Gerontology, University of Southern California, Los Angeles, CA, USA
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13
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Cukierman-Yaffe T, Lee SF, Pare G, McQueen M, Hess S, Gerstein HC. Biomarkers of Prevalent and Incident Cognitive Dysfunction in People with Dysglycemia- Data from the ORIGIN Trial. J Alzheimers Dis 2022; 87:1143-1150. [DOI: 10.3233/jad-215195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Diabetes and cardiovascular disease increase the risk of incident cognitive dysfunction. Identification of novel biochemical markers for cognitive dysfunction may identify people at the highest risk while yielding insights regarding the pathophysiology of cognitive dysfunction. Objective: To identify cardiovascular biomarkers in serum that are independent predictors of cognitive dysfunction in individuals with dysglycemia. Methods: This analysis was conducted in 8,365 participants in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial whose stored serum was analyzed for 238 cardio-metabolic biomarkers and completed a baseline Mini-Mental State Examination (MMSE). Fine and Gray sub distribution hazard models accounting for the competing risk of death accounting for clinical risk factors and the baseline MMSE were used to identify biomarkers that predicted incident cognitive dysfunction (MMSE < 24 or dementia) using forward selection with an inclusion p-value < 0.0002 to account for multiplicity. Results: During a median follow-up period of 6.2 years, 939 individuals developed cognitive dysfunction. After accounting for 17 clinical risk factors, glargine allocation, and the baseline MMSE, three biomarkers (α-2 Macroglobulin, HR 1.19; 95% CI 1.12, 1.27; Macrophage Inflammatory Protein 1α, HR 1.11; 95% CI 1.06, 1.16; and Growth Hormone, HR 0.91; 95% CI 0.87, 0.96) independently predicted incident cognitive dysfunction (p < 0.0002). Addition of these biomarkers to a model that included clinical risk factors, however, did not improve the ability to predict cognitive dysfunction. Conclusion: Addition of independent biomarkers to clinical risk factors for cognitive dysfunction in people with dysglycemia did not predict incident cognitive dysfunction better than clinical risk factors alone.
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Affiliation(s)
- Tali Cukierman-Yaffe
- Endocrinology Institute, Gertner Institute, Sheba Medical Center, Ramat-Gan, Israel
- Epidemiology Department, Sackler School of Medicine, Herceg Institute of Aging, Tel Aviv University, Tel Aviv, Israel
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
| | - Shun-Fu Lee
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
| | - Guillaume Pare
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
- Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada
| | - Matthew McQueen
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
| | - Sibylle Hess
- Sanofi-Aventis Deutschland GmbH, R&D, Translational Medicine & Early Development, Biomarkers & Clinical Bioanalyses, Frankfurt am Main, Germany
| | - Hertzel C. Gerstein
- Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada
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14
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Yang Y, Zhao JJ, Yu XF. Expert Consensus on Cognitive Dysfunction in Diabetes. Curr Med Sci 2022; 42:286-303. [PMID: 35290601 DOI: 10.1007/s11596-022-2549-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 02/02/2022] [Indexed: 12/14/2022]
Abstract
The incidence of diabetes is gradually increasing in China, and diabetes and associated complications, such as cognitive dysfunction have gained much attention in recent time. However, the concepts, clinical treatment, and prevention of cognitive dysfunction in patients with diabetes remain unclear. The Chinese Society of Endocrinology investigated the current national and overseas situation of cognitive dysfunction associated with diabetes. Based on research both in China and other countries worldwide, the Expert Consensus on Cognitive Dysfunction in Diabetes was established to guide physicians in the comprehensive standardized management of cognitive dysfunction in diabetes and to improve clinical outcomes in Chinese patients. This consensus presents an overview, definition and classification, epidemiology and pathogenesis, risk factors, screening, diagnosis, differential diagnosis, treatment, and prevention of cognitive dysfunction in patients with diabetes.
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Affiliation(s)
- Yan Yang
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Jia-Jun Zhao
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 25000, China.
| | - Xue-Feng Yu
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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15
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Lacy ME, Moran C, Gilsanz P, Beeri MS, Karter AJ, Whitmer RA. Comparison of cognitive function in older adults with type 1 diabetes, type 2 diabetes, and no diabetes: results from the Study of Longevity in Diabetes (SOLID). BMJ Open Diabetes Res Care 2022; 10:10/2/e002557. [PMID: 35346969 PMCID: PMC8961108 DOI: 10.1136/bmjdrc-2021-002557] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 03/06/2022] [Indexed: 11/15/2022] Open
Abstract
INTRODUCTION The incidence of both type 1 diabetes (T1D) and type 2 diabetes (T2D) is increasing. Life expectancy is improving in T1D, resulting in a growing population of elderly adults with diabetes. While it is well established that older adults with T2D are at increased risk of cognitive impairment, little is known regarding cognitive aging in T1D and how their cognitive profiles may differ from T2D. RESEARCH DESIGN AND METHODS We compared baseline cognitive function and low cognitive function by diabetes status (n=734 T1D, n=232 T2D, n=247 without diabetes) among individuals from the Study of Longevity in Diabetes (mean age=68). We used factor analysis to group cognition into five domains and a composite measure of total cognition. Using linear and logistic regression models, we examined the associations between diabetes type and cognitive function, adjusting for demographics, comorbidities, depression, and sleep quality. RESULTS T1D was associated with lower scores on total cognition, language, executive function/psychomotor processing speed, and verbal episodic memory, and greater odds of low executive function/psychomotor processing speed (OR=2.99, 95% CI 1.66 to 5.37) and verbal episodic memory (OR=1.92, 95% CI 1.07 to 3.46), compared with those without diabetes. T2D was associated with lower scores on visual episodic memory. Compared with T2D, T1D was associated with lower scores on verbal episodic memory and executive function/psychomotor processing speed and greater odds of low executive function/psychomotor processing speed (OR=1.74, 95% CI 1.03 to 2.92). CONCLUSIONS Older adults with T1D had significantly poorer cognition compared with those with T2D and those without diabetes even after accounting for a range of comorbidities. Future studies should delineate how to reduce risk in this vulnerable population who are newly surviving to old age.
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Affiliation(s)
- Mary E Lacy
- Department of Epidemiology, University of Kentucky, Lexington, Kentucky, USA
- Division of Research, Kaiser Permanente, Oakland, California, USA
| | - Chris Moran
- Academic Unit, Peninsula Clinical School, Monash University Central Clinical School, Melbourne, Victoria, Australia
| | - Paola Gilsanz
- Division of Research, Kaiser Permanente, Oakland, California, USA
| | - Michal S Beeri
- Icahn School of Medicine at Mount Sinai, New York City, New York, USA
- Joseph Sagol Neuroscience, Sheba Medical Center, Tel Hashomer, Israel
| | - Andrew J Karter
- Division of Research, Kaiser Permanente, Oakland, California, USA
| | - Rachel A Whitmer
- Division of Research, Kaiser Permanente, Oakland, California, USA
- Department of Epidemiology, University of California Davis School of Medicine, Davis, California, USA
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16
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Álvarez-Bueno C, Cavero-Redondo I, Bruno RM, Saz-Lara A, Sequí-Dominguez I, Notario-Pacheco B, Martinez-Vizcaino V. Intima Media Thickness and Cognitive Function Among Adults: Meta-Analysis of Observational and Longitudinal Studies. J Am Heart Assoc 2022; 11:e021760. [PMID: 35179392 PMCID: PMC9075078 DOI: 10.1161/jaha.121.021760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Background Carotid structural changes measured by intima media thickness (IMT) have been related to cognitive complaints during aging. Therefore, the aims of this meta‐analysis were (1) to elucidate the relationship between vascular status, measured as IMT, and cognitive domains distinguishing between global cognition, executive functions, memory and attention; and (2) to explore whether demographic (ie, age and sex), clinical (ie, body mass index and IMT baseline values), and procedure characteristics influence this association. Methods and Results We performed a systematic review of MEDLINE (via PubMed), Scopus, and Web of Science databases from their inception to June 2021. Studies meeting the following inclusion criteria were included: (1) the participants were adults; (2) the exposure was carotid IMT; (3) the outcome was cognitive function, including global cognition, executive function, memory, and attention measured using standardized tests; and (4) the study design was cross‐sectional or longitudinal including unadjusted and adjusted analyses. A total of 19 cross‐sectional and 15 longitudinal studies were included and demographic (age and sex), clinical (body mass index and baseline IMT values), and procedure characteristics were analyzed as potential mediator or moderators of the association. Conclusions Our data support negative associations between IMT and cognitive function in cross‐sectional studies. The association between IMT and cognition lost significance in longitudinal studies and when controlling for covariates in cross‐sectional studies. Finally, the strength of these associations seems not to be modified by age, sex, body mass index, and baseline IMT values. This systematic review and meta‐analysis adds to the evidence supporting the use of IMT as a measure for identifying patients at risk of cognitive decline.
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Affiliation(s)
- Celia Álvarez-Bueno
- Health and Social Research Center Universidad de Castilla-La Mancha Cuenca Spain.,Universidad Politécnica y Artística del Paraguay Asunción Paraguay
| | - Iván Cavero-Redondo
- Health and Social Research Center Universidad de Castilla-La Mancha Cuenca Spain.,Rehabilitation in Health Research Center (CIRES)Universidad de las Americas Santiago Chile
| | - Rosa Maria Bruno
- Department of Clinical and Experimental Medicine University of Pisa Italy.,INSERM U970 and Université de Paris Paris France
| | - Alicia Saz-Lara
- Health and Social Research Center Universidad de Castilla-La Mancha Cuenca Spain
| | | | | | - Vicente Martinez-Vizcaino
- Health and Social Research Center Universidad de Castilla-La Mancha Cuenca Spain.,Facultad de Ciencias de la Salud Universidad Autónoma de Chile Talca Chile
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17
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Pawlos A, Broncel M, Woźniak E, Gorzelak-Pabiś P. Neuroprotective Effect of SGLT2 Inhibitors. Molecules 2021; 26:7213. [PMID: 34885795 PMCID: PMC8659196 DOI: 10.3390/molecules26237213] [Citation(s) in RCA: 144] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 11/24/2021] [Accepted: 11/26/2021] [Indexed: 12/17/2022] Open
Abstract
Patients with diabetes are at higher risk of cardiovascular diseases and cognitive impairment. SGLT2 inhibitors (Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Sotagliflozin) are newer hypoglycemic agents with many pleiotropic effects. In this review, we discuss their neuroprotective potential. SGLT2 inhibitors (SGLT2i) are lipid-soluble and reach the brain/serum ratio from 0.3 to 0.5. SGLT receptors are present in the central nervous system (CNS). Flozins are not fully SGLT2-selective and have an affinity for the SGLT1 receptor, which is associated with protection against ischemia/reperfusion brain damage. SGLT2i show an anti-inflammatory and anti-atherosclerotic effect, including reduction of proinflammatory cytokines, M2 macrophage polarization, JAK2/STAT1 and NLRP3 inflammasome inhibition, as well as cIMT regression. They also mitigate oxidative stress. SGLT2i improve endothelial function, prevent remodeling and exert a protective effect on the neurovascular unit, blood-brain barrier, pericytes, astrocytes, microglia, and oligodendrocytes. Flozins are also able to inhibit AChE, which contributes to cognitive improvement. Empagliflozin significantly increases the level of cerebral BDNF, which modulates neurotransmission and ensures growth, survival, and plasticity of neurons. Moreover, they may be able to restore the circadian rhythm of mTOR activation, which is quite a novel finding in the field of research on metabolic diseases and cognitive impairment. SGLT2i have a great potential to protect against atherosclerosis and cognitive impairment in patients with type 2 diabetes mellitus.
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Affiliation(s)
| | - Marlena Broncel
- Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1/5, 91-347 Lodz, Poland; (A.P.); (E.W.); (P.G.-P.)
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18
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Bergantin LB. Diabetes and inflammatory diseases: An overview from the perspective of Ca 2+/3'-5'-cyclic adenosine monophosphate signaling. World J Diabetes 2021; 12:767-779. [PMID: 34168726 PMCID: PMC8192245 DOI: 10.4239/wjd.v12.i6.767] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 12/29/2020] [Accepted: 03/07/2021] [Indexed: 02/06/2023] Open
Abstract
A large amount of evidence has supported a clinical link between diabetes and inflammatory diseases, e.g., cancer, dementia, and hypertension. In addition, it is also suggested that dysregulations related to Ca2+ signaling could link these diseases, in addition to 3'-5'-cyclic adenosine monophosphate (cAMP) signaling pathways. Thus, revealing this interplay between diabetes and inflammatory diseases may provide novel insights into the pathogenesis of these diseases. Publications involving signaling pathways related to Ca2+ and cAMP, inflammation, diabetes, dementia, cancer, and hypertension (alone or combined) were collected by searching PubMed and EMBASE. Both signaling pathways, Ca2+ and cAMP signaling, control the release of neurotransmitters and hormones, in addition to neurodegeneration, and tumor growth. Furthermore, there is a clear relationship between Ca2+ signaling, e.g., increased Ca2+ signals, and inflammatory responses. cAMP also regulates pro- and anti-inflammatory responses. Due to the experience of our group in this field, this article discusses the role of Ca2+ and cAMP signaling in the correlation between diabetes and inflammatory diseases, including its pharmacological implications. As a novelty, this article also includes: (1) A timeline of the major events in Ca2+/cAMP signaling; and (2) As coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving situation, this article also discusses recent reports on the role of Ca2+ channel blockers for preventing Ca2+ signaling disruption due to COVID-19, including the correlation between COVID-19 and diabetes.
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19
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Barzilay JI, Younes N, Pop-Busui R, Florez H, Seaquist E, Falck-Ytter C, Luchsinger JA. The cross-sectional association of renal dysfunction with tests of cognition in middle-aged adults with early type 2 diabetes: The GRADE Study. J Diabetes Complications 2021; 35:107805. [PMID: 33288412 PMCID: PMC7870547 DOI: 10.1016/j.jdiacomp.2020.107805] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 11/17/2020] [Accepted: 11/17/2020] [Indexed: 11/28/2022]
Abstract
OBJECTIVE The association of renal dysfunction with tests of cognition in type 2 diabetes has been examined in individuals with moderate and advanced renal disease. Here we examine the association of renal dysfunction with tests of cognition in a cohort of middle-aged adults with short duration diabetes (mean 4.0 ± 2.8 years). METHODS Baseline data were examined from the Glycemia Reduction Approaches in Diabetes (GRADE) study (n = 4998). Renal dysfunction was defined by the presence of albumin in the urine or by estimated glomerular filtration rate (eGFR). Cognition was assessed with the Spanish English Verbal Learning Test, Letter and Animal fluency tests, and the Digit Symbol Substitution Test. RESULTS Participants with albuminuria or eGFR <60 ml/min/1.73 m2 had significantly lower test scores of information processing speed and perception, executive function and ability to categorize information, and of verbal learning and memory compared to participants without renal disease. Adjustment for hypertension, dyslipidemia, and waist circumference attenuated many of these findings but markers of impaired learning and executive function continued to remain lower in association with higher urine albumin levels. CONCLUSION In type 2 diabetes of short duration, there are already subtle deficiencies in markers of cognition in association with renal disease in middle aged adults.
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Affiliation(s)
- Joshua I Barzilay
- Kaiser Permanente of Georgia, Division of Endocrinology, Atlanta, GA, United States of America; Division of Endocrinology, Emory University School of Medicine, Atlanta, GA, United States of America.
| | - Naji Younes
- The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Rockville, MD, United States of America
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America
| | - Hermes Florez
- GRECC Miami VA Healthcare System, University of Miami, Miami, FL, United States of America
| | - Elizabeth Seaquist
- Division of Diabetes and Endocrinology, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, United States of America
| | - Corinna Falck-Ytter
- Department of Medicine, VA North East Ohio Healthcare System, Case Western Reserve University, Cleveland, OH, United States of America
| | - Jose A Luchsinger
- Columbia University Irving Medical Center, Department of Medicine, New York, NY, United States of America; Columbia University Irving Medical Center, Department of Epidemiology, New York, NY, United States of America
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20
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Clark CE, Warren FC, Boddy K, McDonagh STJ, Moore SF, Goddard J, Reed N, Turner M, Alzamora MT, Ramos Blanes R, Chuang SY, Criqui M, Dahl M, Engström G, Erbel R, Espeland M, Ferrucci L, Guerchet M, Hattersley A, Lahoz C, McClelland RL, McDermott MM, Price J, Stoffers HE, Wang JG, Westerink J, White J, Cloutier L, Taylor RS, Shore AC, McManus RJ, Aboyans V, Campbell JL. Associations Between Systolic Interarm Differences in Blood Pressure and Cardiovascular Disease Outcomes and Mortality: Individual Participant Data Meta-Analysis, Development and Validation of a Prognostic Algorithm: The INTERPRESS-IPD Collaboration. Hypertension 2020; 77:650-661. [PMID: 33342236 PMCID: PMC7803446 DOI: 10.1161/hypertensionaha.120.15997] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02-1.08) and 1.06 (95% CI, 1.02-1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01-1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00-1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01-1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06-1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227.
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Affiliation(s)
- Christopher E Clark
- From the Primary Care Research Group, Institute of Health Services Research (C.E.C., F.C.W., S.T.J.M., S.F.M., R.S.T., J.L.C.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - Fiona C Warren
- From the Primary Care Research Group, Institute of Health Services Research (C.E.C., F.C.W., S.T.J.M., S.F.M., R.S.T., J.L.C.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - Kate Boddy
- Patient and Public Involvement Team, PenCLAHRC (K.B., J.G., N.R., M.T.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - Sinead T J McDonagh
- From the Primary Care Research Group, Institute of Health Services Research (C.E.C., F.C.W., S.T.J.M., S.F.M., R.S.T., J.L.C.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - Sarah F Moore
- From the Primary Care Research Group, Institute of Health Services Research (C.E.C., F.C.W., S.T.J.M., S.F.M., R.S.T., J.L.C.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - John Goddard
- Patient and Public Involvement Team, PenCLAHRC (K.B., J.G., N.R., M.T.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - Nigel Reed
- Patient and Public Involvement Team, PenCLAHRC (K.B., J.G., N.R., M.T.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - Malcolm Turner
- Patient and Public Involvement Team, PenCLAHRC (K.B., J.G., N.R., M.T.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - Maria Teresa Alzamora
- Unitat de Suport a la Recerca Metropolitana Nord, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Mataró, Spain (M.T.A.)
| | - Rafel Ramos Blanes
- Unitat de Suport a la Recerca Girona, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Institut d'Investigació Biomèdica de Girona (IdIBGi), Department of Medical Sciences, School of Medicine, University of Girona, Spain (R.R.B.)
| | - Shao-Yuan Chuang
- Institute of Population Health Sciences, National Health Research Institutes (NHRI), Taiwan, R.O.C (S.-Y.C.)
| | - Michael Criqui
- Department of Family Medicine and Public Health, University of California, San Diego, School of Medicine, La Jolla (M.C.)
| | - Marie Dahl
- Vascular Research Unit, Department of Vascular Surgery, Viborg Regional Hospital, Heibergs Allé 4, 8800 Viborg, Denmark (M.D.).,Department of Clinical Medicine, Aarhus University, Denmark (M.D.)
| | - Gunnar Engström
- Department of Clinical Science in Malmö, Lund University, Sweden (G.E.)
| | - Raimund Erbel
- Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Germany (R.E.)
| | | | | | - Maëlenn Guerchet
- INSERM U1094 & IRD, Tropical Neuroepidemiology, Institut d'Epidémiologie et de Neurologie Tropicale (IENT), Faculté de Médecine de l'Université de Limoges, Limoges Cedex, France (M.G., V.A.)
| | - Andrew Hattersley
- Institute of Biomedical and Clinical Science (A.H.), University of Exeter Medical School, College of Medicine & Health, Devon, England
| | - Carlos Lahoz
- Lípid and Vascular Risk Unit, Internal Medicine Service, Carlos III, La Paz Hospital, Madrid, Spain (C.L.)
| | | | - Mary M McDermott
- Northwestern University Feinberg School of Medicine, Chicago, IL (M.M.M.)
| | - Jackie Price
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Scotland (J.P.)
| | - Henri E Stoffers
- Department of Family Medicine, CAPHRI Care and Public Health Research Institute, Maastricht University, the Netherlands (H.E.S.)
| | - Ji-Guang Wang
- Centre for Epidemiological Studies and Clinical Trials, Shanghai Key Laboratory of Hypertension, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (J.-G.W.)
| | - Jan Westerink
- Department of Vascular Medicine, University Medical Center Utrecht, the Netherlands (J. Westerink)
| | - James White
- DECIPHer, Centre for Trials Research, College of Biomedical and Life Sciences, Cardiff University, Wales (J. White)
| | - Lyne Cloutier
- Département des Sciences Infirmières, Université du Québec à Trois-Rivières, Canada (L.C.)
| | - Rod S Taylor
- From the Primary Care Research Group, Institute of Health Services Research (C.E.C., F.C.W., S.T.J.M., S.F.M., R.S.T., J.L.C.), University of Exeter Medical School, College of Medicine & Health, Devon, England.,MRC/CSO Social and Public Health Sciences Unit & Robertson Centre for Biostatistics, Institute of Health and Well Being, University of Glasgow, Scotland (R.S.T.)
| | - Angela C Shore
- NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital and University of Exeter College of Medicine & Health, England (A.C.S.)
| | - Richard J McManus
- Nuffield Department of Primary Care Health Sciences, University of Oxford, England (R.J.M.)
| | - Victor Aboyans
- Department of Cardiology, Dupuytren University Hospital, and Inserm 1094, Tropical Neuroepidemiology, Limoges, France (V.A.)
| | - John L Campbell
- From the Primary Care Research Group, Institute of Health Services Research (C.E.C., F.C.W., S.T.J.M., S.F.M., R.S.T., J.L.C.), University of Exeter Medical School, College of Medicine & Health, Devon, England
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21
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McGrath ER, Himali JJ, Levy D, Conner SC, DeCarli C, Pase MP, Ninomiya T, Ohara T, Courchesne P, Satizabal CL, Vasan RS, Beiser AS, Seshadri S. Growth Differentiation Factor 15 and NT-proBNP as Blood-Based Markers of Vascular Brain Injury and Dementia. J Am Heart Assoc 2020; 9:e014659. [PMID: 32921207 PMCID: PMC7792414 DOI: 10.1161/jaha.119.014659] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background GDF15 (growth differentiation factor 15) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) may offer promise as biomarkers for cognitive outcomes, including dementia. We determined the association of these biomarkers with cognitive outcomes in a community‐based cohort. Methods and Results Plasma GDF15 (n=1603) and NT‐proBNP levels (n=1590) (53% women; mean age, 68.7 years) were measured in dementia‐free Framingham Offspring cohort participants at examination 7 (1998–2001). Participants were followed up for incident dementia. Secondary outcomes included Alzheimer disease dementia, magnetic resonance imaging structural brain measures, and neurocognitive performance. During a median 11.8‐year follow‐up, 131 participants developed dementia. On multivariable Cox proportional‐hazards analysis, higher circulating GDF15 was associated with an increased risk of incident all‐cause and Alzheimer disease dementia (hazard ratio [HR] per SD increment in natural log‐transformed biomarker value, 1.54 [95% CI, 1.22–1.95] and 1.37 [95% CI, 1.03–1.81], respectively), whereas higher plasma NT‐proBNP was also associated with an increased risk of all‐cause dementia (HR, 1.32; 95% CI, 1.05–1.65). Elevated GDF15 was associated with lower total brain and hippocampal volumes, greater white matter hyperintensity volume, and poorer cognitive performance. Elevated NT‐proBNP was associated with greater white matter hyperintensity volume and poorer cognitive performance. Addition of both biomarkers to a conventional risk factor model improved dementia risk classification (net reclassification improvement index, 0.25; 95% CI, 0.05–0.45). Conclusions Elevated plasma GDF15 and NT‐proBNP were associated with vascular brain injury on magnetic resonance imaging, poorer neurocognitive performance, and increased risk of incident dementia in individuals aged >60 years. Both biomarkers improved dementia risk classification beyond that of traditional clinical risk factors, indicating their potential value in predicting incident dementia.
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Affiliation(s)
- Emer R McGrath
- HRB Clinical Research Facility National University of Ireland Galway Galway Ireland.,Framingham Heart Study Framingham MA
| | - Jayandra J Himali
- Framingham Heart Study Framingham MA.,Boston University School of Public Health Boston MA.,Boston University School of Medicine Boston MA.,Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases University of Texas Health Sciences Center San Antonio TX
| | - Daniel Levy
- Framingham Heart Study Framingham MA.,Population Sciences Branch National Heart, Lung, and Blood Institutes of Health Bethesda MD
| | - Sarah C Conner
- Framingham Heart Study Framingham MA.,Boston University School of Medicine Boston MA
| | | | - Matthew P Pase
- Framingham Heart Study Framingham MA.,Turner Institute Monash University Clayton Victoria Australia.,Harvard University Boston MA Australia
| | - Toshiharu Ninomiya
- Department of Epidemiology and Public Health Graduate School of Medical Sciences Kyushu University Fukuoka Japan
| | - Tomoyuki Ohara
- Department of Epidemiology and Public Health Graduate School of Medical Sciences Kyushu University Fukuoka Japan
| | | | - Claudia L Satizabal
- Framingham Heart Study Framingham MA.,Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases University of Texas Health Sciences Center San Antonio TX
| | - Ramachandran S Vasan
- Framingham Heart Study Framingham MA.,Boston University School of Medicine Boston MA
| | - Alexa S Beiser
- Framingham Heart Study Framingham MA.,Boston University School of Public Health Boston MA.,Boston University School of Medicine Boston MA
| | - Sudha Seshadri
- Framingham Heart Study Framingham MA.,Boston University School of Medicine Boston MA.,Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases University of Texas Health Sciences Center San Antonio TX
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22
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Zhou J, Zhang Z, Zhou H, Qian G. Diabetic Cognitive Dysfunction: From Bench to Clinic. Curr Med Chem 2020; 27:3151-3167. [PMID: 30727866 DOI: 10.2174/1871530319666190206225635] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 12/30/2018] [Accepted: 01/30/2019] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes increases the risk of developing cognitive dysfunction in the elderly in the form of short-term memory and executive function impairment. Genetic and diet-induced models of type 2 diabetes further support this link, displaying deficits in working memory, learning, and memory performance. The risk factors for diabetic cognitive dysfunction include vascular disease, hypoglycaemia, hyperlipidaemia, adiposity, insulin resistance, lifestyle factors, and genetic factors. Using neuronal imaging technologies, diabetic patients with cognitive dysfunction show atrophy of the whole brain, particularly the grey matter, hippocampus and amygdala; increased volume of the ventricular and white matter; brain infarcts; impaired network integrity; abnormal microstructure; and reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis of type 2 diabetes with cognitive dysfunction involves hyperglycaemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apoptosis, and disorders of neurotransmitters. Large clinical trials may offer further proof of biomarkers and risk factors for diabetic cognitive dysfunction. Advanced neuronal imaging technologies and novel disease animal models will assist in elucidating the precise pathogenesis and to provide better therapeutic interventions and treatment.
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Affiliation(s)
- Jiyin Zhou
- National Drug Clinical Trial Institution, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
| | - Zuo Zhang
- National Drug Clinical Trial Institution, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
| | - Hongli Zhou
- National Drug Clinical Trial Institution, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
| | - Guisheng Qian
- Institute of Respiratory Diseases, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
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23
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Bergantin LB. A Link Between Brain Insulin Resistance and Cognitive Dysfunctions: Targeting Ca2+/cAMP Signalling. Cent Nerv Syst Agents Med Chem 2020; 20:103-109. [PMID: 31995022 DOI: 10.2174/1871524920666200129121232] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 06/04/2020] [Accepted: 06/06/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND A correlation between cognitive dysfunctions and brain insulin resistance has been established by several clinical and experimental studies. Consistent data support that people diagnosed with brain insulin resistance, resulted from diabetes, have shown an increased risk of presenting cognitive dysfunctions, clinical signs of dementia and depression, then speculating a role of dysregulations related to insulin signalling in these diseases. Furthermore, it is currently discussed that Ca2+ signalling, and its dysregulations, may be a factor which could correlate with brain insulin resistance and cognitive dysfunctions. OBJECTIVE Following this, revealing this interplay between these diseases may provide novel insights into the pathogenesis of such diseases. METHODS Publications covering topics such as Ca2+ signalling, diabetes, depression and dementia (alone or combined) were collected by searching PubMed and EMBASE. RESULTS The controlling of both neurotransmitters/hormones release and neuronal death could be achieved through modulating Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling). CONCLUSION Taking into account our previous reports on Ca2+/cAMP signalling, and considering a limited discussion in the literature on the role of Ca2+/cAMP signalling in the link between cognitive dysfunctions and brain insulin resistance, this article has comprehensively discussed the role of these signalling pathways in this link (between cognitive dysfunctions and brain insulin resistance).
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Affiliation(s)
- Leandro B Bergantin
- Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
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24
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Zhang S, Xue R, Hu R. The neuroprotective effect and action mechanism of polyphenols in diabetes mellitus-related cognitive dysfunction. Eur J Nutr 2019; 59:1295-1311. [PMID: 31598747 DOI: 10.1007/s00394-019-02078-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 08/10/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) is a complex and prevalent metabolic disorder worldwide. Strong evidence has emerged that DM is a risk factor for the accelerated rate of cognitive decline and the development of dementia. Though traditional pharmaceutical agents are efficient for the management of DM and DM-related cognitive decrement, long-term use of these drugs are along with undesired side effects. Therefore, tremendous studies have focused on the therapeutic benefits of natural compounds at present. Ample evidence exists to prove that polyphenols are capable to modulate diabetic neuropathy with minimal toxicity and adverse effects. PURPOSE To describe the benefits and mechanisms of polyphenols on DM-induced cognitive dysfunction. In this review, we introduce an updated overview of associations between DM and cognitive dysfunction. The risk factors as well as pathological and molecular mechanisms of DM-induced cognitive dysfunction are summarized. More importantly, many active polyphenols that possess preventive and therapeutic effects on DM-induced cognitive dysfunction and the potential signaling pathways involved in the action are highlighted. CONCLUSIONS The therapeutic effects of polyphenols on DM-related cognitive dysfunction pave a novel way for the management of diabetic encephalopathy.
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Affiliation(s)
- Shenshen Zhang
- College of Public Health, Zhengzhou University, Zhengzhou, China.
| | - Ran Xue
- College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Ruizhe Hu
- School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou, China.
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25
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Veugen MGJ, Henry RMA, Brunner-La Rocca HP, Dagnelie PC, Schram MT, van Agtmaal MJM, van der Kallen CJH, Sep SJS, van Boxtel MPJ, Bekers O, Meex SJR, Jansen JFA, Kroon AA, Stehouwer CDA. Cross-Sectional Associations Between Cardiac Biomarkers, Cognitive Performance, and Structural Brain Changes Are Modified by Age. Arterioscler Thromb Vasc Biol 2019; 38:1948-1958. [PMID: 29954754 DOI: 10.1161/atvbaha.118.311082] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Objective- NT-proBNP (N-terminal pro-B-type natriuretic peptide) and cardiac troponin T (cTNT) are associated with cognitive performance. Whether this extends to individuals <60 years of age is unclear. We investigated whether age modified the associations between NT-proBNP and cTNT and cognitive performance and structural brain changes. Approach and Results- In 3011 individuals (60±8 years; 49% women), NT-proBNP and cTNT, memory, information processing speed and executive functioning, grey matter (GM) and white matter, and white matter hyperintensity (WMH) volumes were determined. We used regression, adjusted for educational level, cardiovascular factors, and lifestyle factors, to test whether cross-sectional associations between biomarkers and cognitive performance and structural brain changes were modified by age (<60 versus ≥60 years). ≥60 years, higher NT-proBNP was associated with lower memory (β [SD] per 10-fold higher level [95% confidence interval (CI)], -0.11 [-0.22 to -0.00]), information processing speed (-0.12 [95% CI, -0.21 to -0.03]), executive functioning (-0.12 [95% CI, -0.22 to -0.03]), and smaller GM (β [mL] per 10-fold higher level, -6.89 [95% CI, -11.58 to -2.20]). Additionally, higher cTNT was associated with lower memory (-0.33 [95% CI, -0.53 to -0.12]) and information processing speed (-0.17 [95% CI, -0.3 to -0.01]); with smaller GM (-16.07 [95% CI, -24.90 to -7.24]) and greater WMH (10β WMH per 10-fold higher level, 0.31 [95% CI, 0.10-0.52]). <60 years, NT-proBNP and cTNT were not associated with cognitive performance ( Pinteraction, <0.10). In contrast, higher NT-proBNP was associated with smaller GM (-7.43 [95% CI, -11.70 to -3.16]) and greater WMH (0.13 [95% CI, 0.01-0.25]; Pinteraction,>0.10). Higher cTNT was associated with greater WMH (0.18 [95% CI, -0.01 to 0.37]; Pinteraction,>0.10) but not with GM (0.07 [95% CI, -6.87 to 7.02]; Pinteraction, <0.10). Conclusions- Biomarkers of cardiac injury are continuously associated with structural brain changes in both older and younger individuals but with poorer cognitive performance only in older individuals. These findings stress the continuous nature of the heart-brain axis in the development of cognitive impairment.
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Affiliation(s)
- Marja G J Veugen
- From the Department of Internal Medicine (M.G.J.V., R.M.A.H., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., A.A.K., C.D.A.S.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Ronald M A Henry
- From the Department of Internal Medicine (M.G.J.V., R.M.A.H., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., A.A.K., C.D.A.S.).,Heart and Vascular Centre (R.M.A.H., M.T.S.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Hans-Peter Brunner-La Rocca
- Department of Cardiology (H.-P.B.-L.R.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Pieter C Dagnelie
- Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.).,CAPHRI Care and Public Health Research Institute (P.C.D.).,Department of Epidemiology (P.C.D.)
| | - Miranda T Schram
- From the Department of Internal Medicine (M.G.J.V., R.M.A.H., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., A.A.K., C.D.A.S.).,Heart and Vascular Centre (R.M.A.H., M.T.S.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Marnix J M van Agtmaal
- From the Department of Internal Medicine (M.G.J.V., R.M.A.H., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., A.A.K., C.D.A.S.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Carla J H van der Kallen
- From the Department of Internal Medicine (M.G.J.V., R.M.A.H., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., A.A.K., C.D.A.S.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Simone J S Sep
- From the Department of Internal Medicine (M.G.J.V., R.M.A.H., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., A.A.K., C.D.A.S.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Martin P J van Boxtel
- Department of Psychiatry and Neuropsychology (M.P.J.v.B., J.F.A.J.).,MHeNS School for Mental Health and Neuroscience (M.P.J.v.B.), Maastricht University, the Netherlands
| | - Otto Bekers
- Department of Clinical Chemistry (O.B., S.J.R.M.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Steven J R Meex
- Department of Clinical Chemistry (O.B., S.J.R.M.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Jacobus F A Jansen
- Department of Psychiatry and Neuropsychology (M.P.J.v.B., J.F.A.J.).,Department of Radiology and Nuclear Medicine (J.F.A.J.)
| | - Abraham A Kroon
- From the Department of Internal Medicine (M.G.J.V., R.M.A.H., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., A.A.K., C.D.A.S.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
| | - Coen D A Stehouwer
- From the Department of Internal Medicine (M.G.J.V., R.M.A.H., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., A.A.K., C.D.A.S.).,Maastricht University Medical Center+, the Netherlands; and CARIM School for Cardiovascular Diseases (M.G.J.V., R.M.A.H., H.-P.B.-L.R., P.C.D., M.T.S., M.J.M.v.A., C.J.H.v.d.K., S.J.S.S., O.B., S.J.R.M., A.A.K., C.D.A.S.)
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Xiu S, Liao Q, Sun L, Chan P. Risk factors for cognitive impairment in older people with diabetes: a community-based study. Ther Adv Endocrinol Metab 2019; 10:2042018819836640. [PMID: 31156800 PMCID: PMC6484669 DOI: 10.1177/2042018819836640] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 02/18/2019] [Indexed: 12/16/2022] Open
Abstract
AIM The aim of this study was to investigate the risk factors for cognitive impairment in older people with diabetes. METHODS This cross-sectional study included 2626 community-dwelling participants with diabetes aged ⩾55 years, living in Beijing, China. The participants were screened for risk factors, including smoking, obesity, hypertension, stroke, coronary heart disease, dyslipidemia, depression, apolipoprotein E (APOE) genotype, and low physical activity. Cognitive function was assessed with the scholarship-adjusted Mini-Mental State Examination (MMSE): MMSE ⩽17 for iliterate participants; MMSE ⩽20 for primary school graduates (⩾6 years of education); and MMSE ⩽24 for junior school graduates or above (⩾9 years of education). RESULTS The prevalence of cognitive impairment in older people with diabetes was 9.90%. Multiple logistic regression analysis demonstrated that stroke [odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.20-2.43], less than 0.5 h exercise per day (OR = 1.89, 95% CI = 1.37-2.61), and depression (OR = 1.64, 95% CI = 1.06-2.54), but not smoking, obesity, hypertension, dyslipidemia, and coronary heart disease, were independent risks for cognitive impairment in older people with diabetes. In addition, being married (OR = 0.66, 95% CI = 0.47-0.93) and urban living (OR = 0.33, 95% CI = 0.22-0.48) could decrease the risk of cognitive impairment. CONCLUSIONS Stroke, depression, and less than 0.5 h exercise per day were independent risks for cognitive impairment in older people with diabetes, whereas being married and urban living were protective.
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Affiliation(s)
- Shuangling Xiu
- Department of Endocrinology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China
| | - Qiuju Liao
- Department of Rheumatology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China
| | - Lina Sun
- Department of Endocrinology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China
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Albai O, Frandes M, Timar R, Roman D, Timar B. Risk factors for developing dementia in type 2 diabetes mellitus patients with mild cognitive impairment. Neuropsychiatr Dis Treat 2019; 15:167-175. [PMID: 30655669 PMCID: PMC6322491 DOI: 10.2147/ndt.s189905] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Dementia and cognitive dysfunction have many causes. There is strong evidence that diabetes mellitus (DM) increases the risk of cognitive impairment and dementia. Optimal glycemic control, identification of diabetic risk factors, and prophylactic approach are essential in the prevention of cognitive complications. AIMS The main purpose of this study was to establish the cognitive impairment in DM patients, cared for in the Diabetes Center from Timisoara. Also, we investigated the prevalence of dementia in our group as well as the risk factors involved in the progression of mild cognitive impairment (MCI) to dementia. PATIENTS AND METHODS We considered a sample of 207 type 2 DM (T2DM) patients, aged between 33 and 81 years, mean 57.49 (±11.37) years. We established the diagnosis of dementia based on the Mini-Mental State Examination (MMSE) test, as well as on the psychological testing, psychiatric and neurological investigations, and imaging tests (computerized tomography and MRI). RESULTS A percentage of 42.03% of patients presented MCI, mean age 63 (57.00-71.00) years, being older than patients without MCI, mean age 52.00 (45.00-61.00) years, P<0.001. We observed that diabetes duration was a significant risk factor for developing dementia. Also, patients with MCI presented higher values of body fat than patients without MCI. Moreover, we found that glucose levels, low-density lipoprotein cholesterol levels, the presence of stroke events, and the presence of cardiovascular disease were significant risk factors for MCI conversion to dementia. CONCLUSION Patients with T2DM at early to severe stages of MCI are more likely to develop dementia and should be regularly evaluated for their cognitive status. Regular administrations of the MMSE test can be done to detect early stages of MCI development. Also, to reduce the progression of cognitive impairment to dementia, it is worthwhile to give greater importance to glycemic control and overall DM management.
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Affiliation(s)
- Oana Albai
- Second Department of Internal Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Mirela Frandes
- Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania,
| | - Romulus Timar
- Second Department of Internal Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Deiana Roman
- Municipal Clinical Emergency Hospital, Timisoara, Romania
| | - Bogdan Timar
- Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania,
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Bergman I, Johansson K, Lundberg C. Five-year change scores in old age for six neuropsychological tests and normative data for the Useful Field of View (UFOV) test: The influence of physical health. J Clin Exp Neuropsychol 2018; 41:229-245. [PMID: 30332909 DOI: 10.1080/13803395.2018.1527292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
INTRODUCTION Neuropsychological assessment of cognitive change over time is often conducted in clinical settings, but whether neuropsychological change scores are influenced by physical health has, as far as we know, not been examined previously. METHOD In a sample of 153 older Swedish adults (age range, 72-86 years), we evaluated the influence of common age-related diseases, terminal decline pathology, age, education, and gender, to provide (a) preliminary test-specific regression weights and 90% confidence intervals to assess significant change in performance after five years on tests of visual scanning, mental shifting, visual spatial ability, memory, reaction time, and selective attention, and (b) normative data for the Useful Field of View test (UFOV) from a single testing occasion. RESULTS Multiple regression analyses showed that test-retest changes were affected by physical health for mental shifting, visual spatial ability, memory, and reaction time, by age for mental shifting and visual reaction time, by education for visual spatial ability, and by Age × Education for auditory reaction time. Gender did not affect any of the change scores. The overall average of variance explained was 2.5%: up to 8.1% for physical health, 4.4% for age, and 3.6% for education. The UFOV scores were mostly influenced by age, but also by physical health and education. CONCLUSIONS The findings indicate that considering the influence of health on normative change scores in old age in addition to demographic factors leads to more accurate predictions of whether true change has occurred.
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Affiliation(s)
- Ingvar Bergman
- a Function Area Aging Health and Functioning , Karolinska University Hospital , Stockholm , Sweden.,b Traffic Medicine Centre , Karolinska University Hospital , Stockholm , Sweden
| | - Kurt Johansson
- b Traffic Medicine Centre , Karolinska University Hospital , Stockholm , Sweden.,c Theme Aging , Karolinska University Hospital , Stockholm , Sweden
| | - Catarina Lundberg
- a Function Area Aging Health and Functioning , Karolinska University Hospital , Stockholm , Sweden.,b Traffic Medicine Centre , Karolinska University Hospital , Stockholm , Sweden
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Potential Risk Factors of the Cognitive Dysfunction in Patients with Type 2 Diabetes Mellitus. ROMANIAN JOURNAL OF DIABETES NUTRITION AND METABOLIC DISEASES 2018. [DOI: 10.2478/rjdnmd-2018-0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
It is known that the aged persons with type 2 diabetes mellitus present a high risk for developing neurocognitive disorders and in order to explain this phenomenon we have proposed some potential risk factors. They can be involved in the causality patterns or can act as useful markers of the cerebrovascular lesions (or both) and for which there are strong proofs, including the poor glycemic control, hypoglycemia, microvascular diseases, inflammation or depression. For the macrovascular affections, the association with the cognitive disorders seems to devolve on the examined vascular system. It is put into discussion that for the next researches it is important to analyze how exactly the interrelations between the risk factors can contribute to cognitive disorders.
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30
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Newcombe EA, Camats-Perna J, Silva ML, Valmas N, Huat TJ, Medeiros R. Inflammation: the link between comorbidities, genetics, and Alzheimer's disease. J Neuroinflammation 2018; 15:276. [PMID: 30249283 PMCID: PMC6154824 DOI: 10.1186/s12974-018-1313-3] [Citation(s) in RCA: 373] [Impact Index Per Article: 53.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 09/11/2018] [Indexed: 12/21/2022] Open
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder, most cases of which lack a clear causative event. This has made the disease difficult to characterize and, thus, diagnose. Although some cases are genetically linked, there are many diseases and lifestyle factors that can lead to an increased risk of developing AD, including traumatic brain injury, diabetes, hypertension, obesity, and other metabolic syndromes, in addition to aging. Identifying common factors and trends between these conditions could enhance our understanding of AD and lead to the development of more effective treatments. Although the immune system is one of the body’s key defense mechanisms, chronic inflammation has been increasingly linked with several age-related diseases. Moreover, it is now well accepted that chronic inflammation has an important role in the onset and progression of AD. In this review, the different inflammatory signals associated with AD and its risk factors will be outlined to demonstrate how chronic inflammation may be influencing individual susceptibility to AD. Our goal is to bring attention to potential shared signals presented by the immune system during different conditions that could lead to the development of successful treatments.
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Affiliation(s)
- Estella A Newcombe
- Neurula Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Building 79, Brisbane, 4072, QLD, Australia.
| | - Judith Camats-Perna
- Neurula Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Building 79, Brisbane, 4072, QLD, Australia
| | - Mallone L Silva
- Neurula Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Building 79, Brisbane, 4072, QLD, Australia
| | - Nicholas Valmas
- Queensland Brain Institute, The University of Queensland, Brisbane, 4072, QLD, Australia
| | - Tee Jong Huat
- Neurula Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Building 79, Brisbane, 4072, QLD, Australia.,Centre for Stem Cell Ageing and Regenerative Engineering, The University of Queensland, Brisbane, 4072, QLD, Australia
| | - Rodrigo Medeiros
- Neurula Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Building 79, Brisbane, 4072, QLD, Australia.
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31
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Bertens AS, Sabayan B, de Craen AJM, Van der Mast RC, Gussekloo J. High Sensitivity Cardiac Troponin T and Cognitive Function in the Oldest Old: The Leiden 85-Plus Study. J Alzheimers Dis 2018; 60:235-242. [PMID: 28826179 DOI: 10.3233/jad-170171] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Impaired cardiac function has been related to accelerated cognitive decline in late-life. OBJECTIVE To investigate whether higher levels of high sensitivity cardiac troponin T (hs-cTnT), a sensitive marker for myocardial injury, are associated with worse cognitive function in the oldest old. METHODS In 455 participants of the population-based Leiden 85-plus Study, hs-cTnT was measured at 86 years. Cognitive function was measured annually during four years with the Mini-Mental State Examination (MMSE). RESULTS Participants in the highest gender-specific tertile of hs-cTnT had a 2.0-point lower baseline MMSE score than participants in the lowest tertile (95% confidence interval (CI) (95% CI 0.73-3.3), and had a 0.58-point steeper annual decline in MMSE during follow-up (95% CI 0.06-1.1). The associations remained after adjusting for sociodemographic and cardiovascular risk factors excluding those without a history of overt cardiac disease. CONCLUSION In a population-based sample of the oldest old, higher levels of hs-cTnT were associated with worse cognitive function and faster cognitive decline, independently from cardiovascular risk factors and a history of overt cardiac disease.
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Affiliation(s)
- Anne Suzanne Bertens
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.,Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
| | - Behnam Sabayan
- Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.,Departments of Medicine and Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
| | - Anton J M de Craen
- Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
| | - Roos C Van der Mast
- Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.,Department of Psychiatry, CAPRI-University of Antwerp, Antwerp, Belgium
| | - Jacobijn Gussekloo
- Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.,Department of Public Health and Primary Care, Leiden University Medical Center, The Netherlands
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32
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Zhao X, Han Q, Lv Y, Sun L, Gang X, Wang G. Biomarkers for cognitive decline in patients with diabetes mellitus: evidence from clinical studies. Oncotarget 2017; 9:7710-7726. [PMID: 29484146 PMCID: PMC5800938 DOI: 10.18632/oncotarget.23284] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 10/30/2017] [Indexed: 12/26/2022] Open
Abstract
Diabetes mellitus is considered as an important factor for cognitive decline and dementia in recent years. However, cognitive impairment in diabetic patients is often underestimated and kept undiagnosed, leading to thousands of diabetic patients suffering from worsening memory. Available reviews in this field were limited and not comprehensive enough. Thus, the present review aimed to summarize all available clinical studies on diabetic patients with cognitive decline, and to find valuable biomarkers that might be applied as diagnostic and therapeutic targets of cognitive impairment in diabetes. The biomarkers or risk factors of cognitive decline in diabetic patients could be classified into the following three aspects: serum molecules or relevant complications, functional or metabolic changes by neuroimaging tools, and genetic variants. Specifically, factors related to poor glucose metabolism, insulin resistance, inflammation, comorbid depression, micro-/macrovascular complications, adipokines, neurotrophic molecules and Tau protein presented significant changes in diabetic patients with cognitive decline. Besides, neuroimaging platform could provide more clues on the structural, functional and metabolic changes during the cognitive decline progression of diabetic patients. Genetic factors related to cognitive decline showed inconsistency based on the limited studies. Future studies might apply above biomarkers as diagnostic and treatment targets in a large population, and regulation of these parameters might shed light on a more valuable, sensitive and specific strategy for the diagnosis and treatment of cognitive decline in diabetic patients.
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Affiliation(s)
- Xue Zhao
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China
| | - Qing Han
- Hospital of Orthopedics, The Second Hospital of Jilin University, Changchun, 130021, Jilin Province, China
| | - You Lv
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China
| | - Lin Sun
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China
| | - Xiaokun Gang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China
| | - Guixia Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China
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Morelli NL, Cachioni M, Lopes A, Batistoni SST, Falcão DVDS, Neri AL, Yassuda MS. Verbal fluency in elderly with and without hypertension and diabetes from the FIBRA study in Ermelino Matarazzo. Dement Neuropsychol 2017; 11:413-418. [PMID: 29354222 PMCID: PMC5770000 DOI: 10.1590/1980-57642016dn11-040011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 11/06/2017] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND There are few studies on the qualitative variables derived from the animal category verbal fluency test (VF), especially with data originating from low-income samples of community-based studies. OBJECTIVE To compare elderly with and without hypertension (HTN) and diabetes mellitus (DM) regarding the total number of animals spoken, number of categories, groups and category switches on the VF test. METHODS We used the database of the FIBRA (Frailty in Brazilian Elderly) community-based study. The variables number of Categories, Groups and Category Switches were created for each participant. The total sample (n = 384) was divided into groups of elderly who reported having HTN, DM, both HTN and DM, or neither of these conditions. RESULTS There were no significant differences between the groups with and without these chronic diseases for VF total score or for the qualitative variables. CONCLUSION Among independent community-dwelling elderly, the qualitative variables derived from the VF animal category may not add information regarding the cognitive profile of elderly with chronic diseases. Total VF score and the qualitative variables Category, Group and Switching did not differentiate elderly with and without HTN and DM.
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Affiliation(s)
- Nathalia Lais Morelli
- Gerontologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Meire Cachioni
- Gerontologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, São Paulo, Brazil
- Gerontologia, Faculdade de Ciências Médicas, UNICAMP, Campinas, São Paulo, Brazil
| | - Andrea Lopes
- Gerontologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Samila Sathler Tavares Batistoni
- Gerontologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, São Paulo, Brazil
- Gerontologia, Faculdade de Ciências Médicas, UNICAMP, Campinas, São Paulo, Brazil
| | | | - Anita Liberalesso Neri
- Gerontologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, São Paulo, Brazil
- Gerontologia, Faculdade de Ciências Médicas, UNICAMP, Campinas, São Paulo, Brazil
| | - Monica Sanches Yassuda
- Gerontologia, Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, São Paulo, Brazil
- Gerontologia, Faculdade de Ciências Médicas, UNICAMP, Campinas, São Paulo, Brazil
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Jenks SJ, Conway BR, McLachlan S, Teoh WL, Williamson RM, Webb DJ, Welsh P, Sattar N, Strachan MWJ, Price JF. Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes. Diabetologia 2017; 60:1400-1408. [PMID: 28528401 PMCID: PMC5491560 DOI: 10.1007/s00125-017-4297-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 04/05/2017] [Indexed: 10/28/2022]
Abstract
AIMS/HYPOTHESIS We investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes. METHODS A cohort of 1066 Scottish men and women aged 60-74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml-1 min-1 (1.73 m)-2 at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models. RESULTS A total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286). CONCLUSIONS/INTERPRETATION Our findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention.
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Affiliation(s)
- Sara J Jenks
- Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, UK.
- Centre for Population Health Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh, EH8 9AG, UK.
| | - Bryan R Conway
- University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Stela McLachlan
- Centre for Population Health Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh, EH8 9AG, UK
| | - Wei Leng Teoh
- Metabolic Unit, Western General Hospital, Edinburgh, UK
| | | | - David J Webb
- University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Paul Welsh
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | | | - Jackie F Price
- Centre for Population Health Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh, EH8 9AG, UK
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Veeranki SP, Downer B, Jupiter D, Wong R. Arthritis and Risk of Cognitive and Functional Impairment in Older Mexican Adults. J Aging Health 2017; 29:454-473. [PMID: 26965081 PMCID: PMC5017899 DOI: 10.1177/0898264316636838] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE This study investigated the risk of cognitive and functional impairment in older Mexicans diagnosed with arthritis. Participants included 2,681 Mexicans, aged ≥60 years, enrolled in the Mexican Health and Aging Study cohort. METHOD Participants were categorized into arthritis and no arthritis exposure groups. Primary outcome included participants categorized into "cognitively impaired" or "cognitively normal" groups. Secondary outcomes included participants categorized into Normal, Functionally Impaired only, Cognitively Impaired only, or Dementia (both cognitively and functionally impaired) groups. Multivariable logistic and multinomial regression models were used to assess the relationships. RESULTS Overall, 16% or 7% were diagnosed with cognitive impairment or dementia. Compared with older Mexicans without arthritis, those who were diagnosed with arthritis had significantly increased risk of functional impairment (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] = [1.45, 2.29]), but not of dementia. CONCLUSION Arthritis is associated with increased risk of functional impairment, but not with dementia after 11 years in older Mexicans.
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Affiliation(s)
| | - Brian Downer
- University of Texas Medical Branch, Galveston, USA
| | | | - Rebeca Wong
- University of Texas Medical Branch, Galveston, USA
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36
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Burkauskas J, Bunevicius A, Brozaitiene J, Neverauskas J, Lang P, Duwors R, Mickuviene N, Bunevicius R. Cognitive Functioning in Coronary Artery Disease Patients: Associations with Thyroid Hormones, N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein. Arch Clin Neuropsychol 2017; 32:245-251. [PMID: 28119302 DOI: 10.1093/arclin/acx004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 12/29/2016] [Indexed: 11/14/2022] Open
Abstract
Objective To determine whether biomarkers of health such as serum levels of free triiodothyronine (fT3), total triiodothyronine (TT3), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) impact the cognitive functioning of coronary artery disease (CAD) patients. Method About 278 patients were evaluated for socio-demographic and clinical risk factors as well as fT3, TT3, NT-proBNP, and hsCRP serum levels. Cognitive functioning measures included the Mini-Mental State Examination, Digit Span Test, Digit Symbol Substitution Test (DSST), and Trail Making Test A (TMTA). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale. Results Lower fT3 concentrations were associated with longer completion time of the DSST and TMTA. Elevated levels of NT-proBNP were also associated with inferior performance on TMTA independently of socio-demographic characteristics, clinical risk factors, and depression symptoms. Conclusions Lower fT3 concentrations and higher levels of NT-proBNP were associated with worse cognitive functioning in CAD patients.
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Affiliation(s)
- Julius Burkauskas
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga LT-00135, Lithuania
| | - Adomas Bunevicius
- Laboratory of Clinical Research, Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas LT-44307, Lithuania
| | - Julija Brozaitiene
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga LT-00135, Lithuania
| | - Julius Neverauskas
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga LT-00135, Lithuania
| | - Peter Lang
- Harvard Medical School, Laboratory of Clinical & Experimental Psychopathology, Dr John C. Corrigan Mental Health Center, 49 Hillside Street, Fall River, MA 02720, USA
| | - Robert Duwors
- Harvard Medical School, Laboratory of Clinical & Experimental Psychopathology, Dr John C. Corrigan Mental Health Center, 49 Hillside Street, Fall River, MA 02720, USA
| | - Narseta Mickuviene
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga LT-00135, Lithuania
| | - Robertas Bunevicius
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga LT-00135, Lithuania
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Tynkkynen J, Hernesniemi JA, Laatikainen T, Havulinna AS, Salo P, Blankenberg S, Zeller T, Salomaa V. High-sensitivity cardiac troponin I and NT-proBNP as predictors of incident dementia and Alzheimer’s disease: the FINRISK Study. J Neurol 2016; 264:503-511. [DOI: 10.1007/s00415-016-8378-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 12/21/2016] [Indexed: 12/25/2022]
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38
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Saedi E, Gheini MR, Faiz F, Arami MA. Diabetes mellitus and cognitive impairments. World J Diabetes 2016; 7:412-422. [PMID: 27660698 PMCID: PMC5027005 DOI: 10.4239/wjd.v7.i17.412] [Citation(s) in RCA: 134] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 07/23/2016] [Accepted: 08/08/2016] [Indexed: 02/05/2023] Open
Abstract
There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer’s disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings.
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Wendell CR, Waldstein SR, Evans MK, Zonderman AB. Subclinical carotid atherosclerosis and neurocognitive function in an urban population. Atherosclerosis 2016; 249:125-31. [PMID: 27092741 DOI: 10.1016/j.atherosclerosis.2016.04.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 03/16/2016] [Accepted: 04/07/2016] [Indexed: 10/22/2022]
Abstract
BACKGROUND AND AIMS Examine age, sex, race, and socioeconomic status as modifiers of the association between carotid intimal medial thickness (IMT) and neurocognitive performance in a socioeconomically diverse, biracial, urban, adult population. METHODS Participants were 1712 community-dwelling adults (45% men, 56% African-American, 38% below poverty threshold, aged 30-64 years) enrolled in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Participants underwent initial carotid ultrasonography followed by cognitive testing on up to two occasions over 4 years. Mixed-effects regression analyses were adjusted for demographic, behavioral, and biomedical covariates. RESULTS Significant cross-sectional IMT × race × poverty interactions were identified for measures of delayed recall memory, auditory-verbal attention, and working memory. An IMT × race interaction also appeared for auditory-verbal learning. Higher IMT was generally associated with worse cognitive performance, but the disadvantage was most pronounced among those with higher socioeconomic status and white participants. No longitudinal associations were identified. CONCLUSIONS Carotid IMT-cognition associations differed as a function of race and socioeconomic status and were most compelling for measures of attention, executive function, and memory. These findings highlight the possibility that subclinical atherosclerosis may be differentially informative as a predictor of cognitive performance among varied demographic subgroups.
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Affiliation(s)
- Carrington R Wendell
- Department of Psychology, University of Maryland, Baltimore County, USA; Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, NIH, USA.
| | - Shari R Waldstein
- Department of Psychology, University of Maryland, Baltimore County, USA; Division of Gerontology & Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, USA; Geriatric Research Education and Clinical Center, Baltimore VA Medical Center, USA
| | - Michele K Evans
- Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, NIH, USA
| | - Alan B Zonderman
- Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, NIH, USA
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Prinz N, Stingl J, Dapp A, Denkinger MD, Fasching P, Jehle PM, Merger S, Mühldorfer S, Pieper U, Schuler A, Zeyfang A, Holl RW. High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: A multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry. Diabetes Res Clin Pract 2016; 112:73-81. [PMID: 26563590 DOI: 10.1016/j.diabres.2015.10.026] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 10/13/2015] [Accepted: 10/20/2015] [Indexed: 12/14/2022]
Abstract
AIMS Dementia and type 2 diabetes (T2D) are two major phenomena in older people. To compare anti-hyperglycemic therapy and diabetes-related comorbidities between elderly T2D patients with or without comorbid dementia. METHODS 215,932 type 2 diabetes patients aged ≥ 40 years (median [Q1;Q3]: 70.4 [61.2;77.7] years) from the standardized, multicenter German/Austrian diabetes patient registry, DPV, were studied. To identify patients with comorbid dementia, the registry was searched by ICD-10 codes, DSM-IV/-5 codes, respective search terms and/or disease-specific medication. For group comparisons, multiple hierarchic regression modeling with adjustments for age, sex, and duration of diabetes was applied. RESULTS 3.1% (n=6770; 57% females) of the eligible T2D patients had clinically recognized comorbid dementia. After adjustment for demographics, severe hypoglycemia (insulin group: 14.8 ± 0.6 vs. 10.4 ± 0.2 events per 100 patient-years, p<0.001), hypoglycemia with coma (insulin group: 7.6 ± 0.4 vs. 3.9 ± 0.1 events per 100 patient-years, p<0.001), depression (9.9 vs. 4.7%, p<0.001), hypertension (74.7 vs. 72.2%, p<0.001), stroke (25.3 vs. 6.5%, p<0.001), diabetic foot syndrome (6.0 vs. 5.2%, p=0.004), and microalbuminuria (34.7 vs. 32.2%, p<0.001) were more common in dementia patients compared to T2D without dementia. Moreover, patients with dementia received insulin therapy more frequently (59.3 vs. 54.7%, p<0.001), but metabolic control (7.7 ± 0.1 vs. 7.7 ± 0.1%) was comparable to T2D without dementia. CONCLUSIONS In T2D with dementia, higher rates of hypoglycemia and other diabetes-related comorbidities were observed. Hence, the risks of a glucocentric and intense diabetes management with insulin and a focus on tight glycemic control without considering other factors may outweigh the benefits in elderly T2D patients with comorbid dementia.
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Affiliation(s)
- Nicole Prinz
- Institute of Epidemiology and Medical Biometry, Central Institute for Biomedical Technology, University of Ulm and German Center for Diabetes Research (DZD), Ulm, Germany.
| | - Julia Stingl
- Federal Institute for Drugs and Medical Devices, and Faculty of Medicine, University of Bonn, Bonn, Germany
| | - Albrecht Dapp
- Diabetes Center, Hospital District Tuttlingen, Medical Clinic Spaichingen, Spaichingen, Germany
| | - Michael D Denkinger
- Geriatric Center Ulm/Alb-Donau, Geriatric Medicine at Ulm University, Agaplesion Bethesda Hospital Ulm, Ulm, Germany
| | - Peter Fasching
- 5th Medical Department, Wilhelminenspital, Vienna, Austria
| | - Peter M Jehle
- Department of Internal Medicine, Paul-Gerhardt-Stift, Academic hospital of the Martin-Luther-University Halle-Wittenberg, Lutherstadt Wittenberg, Germany
| | - Sigrun Merger
- Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | | | - Urte Pieper
- Department of Internal Medicine, Hospital Wolgast, Wolgast, Germany
| | - Andreas Schuler
- Department of Internal Medicine, Helfenstein Hospital Geislingen/Steige, Geislingen/Steige, Germany
| | - Andrej Zeyfang
- Institute of Epidemiology and Medical Biometry, Central Institute for Biomedical Technology, University of Ulm and German Center for Diabetes Research (DZD), Ulm, Germany; Agaplesion Bethesda Hospital Stuttgart, Germany
| | - Reinhard W Holl
- Institute of Epidemiology and Medical Biometry, Central Institute for Biomedical Technology, University of Ulm and German Center for Diabetes Research (DZD), Ulm, Germany
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Vieira ER, Mendy A, Prado CM, Gasana J, Albatineh AN. Falls, physical limitations, confusion and memory problems in people with type II diabetes, undiagnosed diabetes and prediabetes, and the influence of vitamins A, D and E. J Diabetes Complications 2015; 29:1159-64. [PMID: 26344725 DOI: 10.1016/j.jdiacomp.2015.08.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 08/06/2015] [Accepted: 08/07/2015] [Indexed: 11/16/2022]
Abstract
AIMS To examine the association between type II diabetes, prediabetes and undiagnosed diabetes with falls, physical limitations, confusion and memory problems, and to evaluate the effects of vitamins A, D and E levels on the associations. METHODS Data from 37,973 participants of the National Health and Nutrition Examination Survey was analyzed. RESULTS The participants' mean age was 46±17years, 20% had diabetes of which 17% were unaware of their condition (undiagnosed diabetes), and 21% had prediabetes. Diabetes was significantly associated with falls, difficulties in stooping, crouching, kneeling, completing house chores, getting in and out bed, standing and sitting for long periods, reaching over head, grasping, holding objects, and attending social events. The association between diabetes and confusion or memory problems was stronger for those diagnosed before age 40. Memory problems were reported only by people with diabetes with lower vitamin D levels. Vitamin A and E levels did not modify the association between diabetes and falls or any of the physical functions, confusion or memory problems. Prediabetes was only associated with difficulty standing for long periods. CONCLUSIONS Diabetes was associated with falls, difficulties in physical functioning and attending social events. Vitamin D levels modified the effects on confusion and memory problems.
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Affiliation(s)
- Edgar R Vieira
- Departments of Physical Therapy & Neuroscience, Florida International University, Miami, Florida, US.
| | - Angelico Mendy
- Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, US
| | - Carla M Prado
- Department of Agricultural, Food & Nutritional Science, & Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
| | - Janvier Gasana
- South Florida Asthma Consortium, Fort Lauderdale, Florida, US
| | - Ahmed N Albatineh
- Department of Community Medicine and Behavioral Sciences, Faculty of Medicine, Kuwait University, Kuwait
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Heath CA, Mercer SW, Guthrie B. Vascular comorbidities in younger people with dementia: a cross-sectional population-based study of 616 245 middle-aged people in Scotland. J Neurol Neurosurg Psychiatry 2015; 86:959-64. [PMID: 25406350 DOI: 10.1136/jnnp-2014-309033] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Accepted: 10/15/2014] [Indexed: 11/04/2022]
Abstract
INTRODUCTION There is growing evidence of an aetiological relationship between vascular risk factors and the development of dementia in later life. Dementia in the under-65s has historically been considered to be more driven by genetic factors, but previous epidemiological studies in the young have been relatively small. This study aims to determine the prevalence of vascular comorbidity in people aged <65 with dementia in comparison to the general population. METHODS Analysis of routine clinical data from 314 (30%) general medical practices in Scotland. RESULTS From an overall population of 616 245 individuals, 1061 cases of 'all-cause' dementia were identified (prevalence 172/100 000 population, 95% CI 161 to 182). The prevalence of dementia was higher in people with vascular morbidities, and prevalence progressively increased from 129/100 000 in people with no vascular comorbidity to 999/100 000 in people with four or more (p=0.01). The strength of association was greatest with a previous transient ischaemic attack (TIA) or stroke and chronic kidney disease (adjusted OR=3.1 and 2.9, respectively). Statistically significant, but smaller associations were seen with the presence of hypertension, diabetes, ischaemic heart disease and peripheral vascular disease (adjusted OR=1.4, 2.0, 1.9 and 2.2, respectively). DISCUSSIONS Vascular comorbid diseases were more commonly recorded in people aged 40-64 with dementia than those without. This finding indicates that vascular disease may be more important in the aetiology of young-onset dementia than previously believed, and is of concern given the continuing rise in obesity and diabetes internationally.
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Affiliation(s)
- C A Heath
- Department of Neurology, Ninewells Hospital, Dundee, UK
| | - S W Mercer
- Department of Primary Care, University of Glasgow, Glasgow, UK
| | - B Guthrie
- Department of Primary Care Medicine, University of Dundee, Dundee, UK
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Feinkohl I, Keller M, Robertson CM, Morling JR, McLachlan S, Frier BM, Deary IJ, Strachan MWJ, Price JF. Cardiovascular risk factors and cognitive decline in older people with type 2 diabetes. Diabetologia 2015; 58:1637-45. [PMID: 25847351 PMCID: PMC4473016 DOI: 10.1007/s00125-015-3581-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Accepted: 03/16/2015] [Indexed: 12/30/2022]
Abstract
AIMS/HYPOTHESIS The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS A baseline history of moderate/heavy smoking (≥ 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised β range -0.07 to -0.14; all p ≤ 0.05). CONCLUSIONS/INTERPRETATION Increased smoking and poorer glycaemic control (with relatively weaker findings for BP) during the life-course were independently associated with accelerated late-life cognitive decline. Where possible, evaluation is warranted of these risk factors as targets for intervention to reduce the burden of cognitive impairment in diabetes.
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Affiliation(s)
- Insa Feinkohl
- Centre for Population Health Sciences, Medical School, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK,
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Feinkohl I, Price JF, Strachan MWJ, Frier BM. The impact of diabetes on cognitive decline: potential vascular, metabolic, and psychosocial risk factors. ALZHEIMERS RESEARCH & THERAPY 2015; 7:46. [PMID: 26060511 PMCID: PMC4460635 DOI: 10.1186/s13195-015-0130-5] [Citation(s) in RCA: 115] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Accepted: 05/20/2015] [Indexed: 12/31/2022]
Abstract
Older people with type 2 diabetes are at increased risk of developing cognitive impairment, for which several potential risk factors have been proposed. The present article reviews evidence in people with type 2 diabetes for associations of cognitive impairment with a range of vascular, metabolic, and psychosocial risk factors, many of which have a higher prevalence in people with type 2 diabetes than in non-diabetic adults of a similar age. Definitive research studies in this field are few in number. The risk factors may be involved in causal pathways or may act as useful markers of cerebrovascular damage (or both), and for which relatively consistent evidence is available, include poor glycemic control, hypoglycemia, microvascular disease, inflammation, and depression. For macrovascular disease, the strength of the association with cognitive impairment appears to depend on which vascular system has been examined. A role for pre-morbid ability in young adulthood as influencing the risk of both diabetes and cognitive impairment has also been suggested. The importance of considering inter-relationships between risk factors when investigating their potential contribution to cognitive impairment in future investigations is discussed.
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Affiliation(s)
- Insa Feinkohl
- Centre for Population Health Sciences, Medical School, Teviot Place, Edinburgh, EH8 9AG Scotland UK
| | - Jackie F Price
- Centre for Population Health Sciences, Medical School, Teviot Place, Edinburgh, EH8 9AG Scotland UK
| | - Mark W J Strachan
- Metabolic Unit, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU Scotland UK
| | - Brian M Frier
- The Queen's Medical Research Institute, University of Edinburgh, College of Medical and Veterinary Medicine, 47 Little France Crescent, Edinburgh, EH16 4TJ Scotland UK
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Koekkoek PS, Kappelle LJ, van den Berg E, Rutten GEHM, Biessels GJ. Cognitive function in patients with diabetes mellitus: guidance for daily care. Lancet Neurol 2015; 14:329-40. [PMID: 25728442 DOI: 10.1016/s1474-4422(14)70249-2] [Citation(s) in RCA: 257] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Diabetes mellitus is associated with an increase in the risk of dementia and the proportion of patients who convert from mild cognitive impairment (MCI) to dementia. In addition to MCI and dementia, the stages of diabetes-associated cognitive dysfunction include subtle cognitive changes that are unlikely to affect activities of daily life or diabetes self-management. These diabetes-associated cognitive decrements have structural brain correlates detectable with brain MRI, but usually show little progression over time. Although cognitive decrements do not generally represent a pre-dementia stage in patients below the age of 60-65 years, in older individuals these subtle cognitive changes might represent the earliest stages of a dementia process. Acknowledgment of diabetes-associated cognitive decrements can help to improve understanding of patients' symptoms and guide management. Future challenges are to establish the importance of screening for cognitive impairment in people with diabetes, to identify those at increased risk of accelerated cognitive decline at an early stage, and to develop effective treatments.
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Affiliation(s)
- Paula S Koekkoek
- Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Netherlands
| | - L Jaap Kappelle
- Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht, Netherlands.
| | - Esther van den Berg
- Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht, Netherlands; Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, Netherlands
| | - Guy E H M Rutten
- Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Netherlands
| | - Geert Jan Biessels
- Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht, Netherlands
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Formiga F, Reñe R, Pérez-Maraver M. Demencia y diabetes: ¿relación casual o causal? Med Clin (Barc) 2015; 144:176-80. [DOI: 10.1016/j.medcli.2014.01.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 01/24/2014] [Accepted: 01/30/2014] [Indexed: 01/03/2023]
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Price AH, Welsh P, Weir CJ, Feinkohl I, Robertson CM, Morling JR, McLachlan S, Strachan MWJ, Sattar N, Price JF. N-terminal pro-brain natriuretic peptide and risk of cardiovascular events in older patients with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetologia 2014; 57:2505-12. [PMID: 25231020 DOI: 10.1007/s00125-014-3375-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Accepted: 08/26/2014] [Indexed: 12/22/2022]
Abstract
AIMS/HYPOTHESIS The aim of this study was to investigate the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with traditional cardiovascular risk factors and incident cardiovascular events in older people with type 2 diabetes. METHODS In the prospective phase of the Edinburgh Type 2 Diabetes Study, 1066 men and women aged 60 to 75 years with type 2 diabetes mellitus were followed for 4 years; 112 participants had an incident cardiovascular event. At baseline, cardiovascular risk factors, pre-existing cardiovascular disease and levels of NT-proBNP were evaluated. RESULTS Raised plasma NT-proBNP levels were associated with these classical cardiovascular risk factors: increased duration of diabetes, use of insulin, raised BMI, reduced HDL-cholesterol, reduced renal function and use of lipid-lowering and anti-hypertensive medication (all p < 0.05). In the prospective analysis, NT-proBNP was strongly associated with subsequent risk of all cardiovascular disease events (HR per one SD increase in NT-proBNP 1.39; 95% CI 1.10, 1.75), independent of cardiovascular risk factors traditionally used to predict vascular events. NT-proBNP was also independently associated with incident coronary artery disease events (1.48, 95% CI 1.10, 1.98). The addition of NT-proBNP to multivariate models improved the C-index by 0.019 for the 'hard' cardiac endpoint (fatal and non-fatal myocardial infarction). CONCLUSIONS/INTERPRETATION In older people with type 2 diabetes, NT-proBNP is associated with the development of coronary and cerebrovascular events, independent of a wide range of other vascular and metabolic risk factors, and may prove a useful addition to current vascular risk scores in diabetes populations.
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Affiliation(s)
- Anna H Price
- Centre for Population Health Sciences, The University of Edinburgh Medical School, Teviot Place, Edinburgh, Scotland, EH8 9AG, UK,
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Bedenis R, Price AH, Robertson CM, Morling JR, Frier BM, Strachan MWJ, Price JF. Association between severe hypoglycemia, adverse macrovascular events, and inflammation in the Edinburgh Type 2 Diabetes Study. Diabetes Care 2014; 37:3301-8. [PMID: 25239782 DOI: 10.2337/dc14-0908] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine whether a history of severe hypoglycemia was associated with an increased risk of subsequent macrovascular events in people with type 2 diabetes and to explore possible mediation of this association by inflammation. RESEARCH DESIGN AND METHODS A cohort of 1,066 adults aged 60-75 years with type 2 diabetes was evaluated prospectively. Baseline history of severe hypoglycemia and plasma levels of the inflammatory markers C-reactive protein, fibrinogen, interleukin-6, and tumor necrosis factor-α were recorded. Their association with incident macrovascular events after 4 years was explored. RESULTS At baseline, 87 participants (8.2%) reported one or more episodes of severe hypoglycemia within the preceding year, and at follow-up 99 participants (9.3%) had suffered a new macrovascular event. Hypoglycemia was associated with increased odds of macrovascular events (odds ratio [OR] 2.11 [95% CI 1.06, 4.21], P = 0.035), including coronary heart events (OR 2.44 [95% CI 1.13, 5.26], P = 0.023), largely due to increased myocardial infarction (OR 4.02 [95% CI 1.54, 10.48], P = 0.004). Hypoglycemia was also associated with increased levels of inflammatory markers, including a general inflammation factor derived using principal-components analysis (P = 0.030, after adjustment for cardiometabolic risk factors). However, the significant association between hypoglycemia and macrovascular events persisted after adjustment for inflammatory markers. CONCLUSIONS The odds of suffering a macrovascular event were higher in patients with type 2 diabetes who had a history of severe hypoglycemia. There was no evidence that a proinflammatory state had a major role in mediating this association.
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Affiliation(s)
- Rachel Bedenis
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, U.K.
| | - Anna H Price
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, U.K
| | - Christine M Robertson
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, U.K
| | - Jo R Morling
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, U.K
| | - Brian M Frier
- Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, Scotland, U.K
| | | | - Jackie F Price
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, U.K
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Xu W, Tan L, Yu JT. The Role of PICALM in Alzheimer's Disease. Mol Neurobiol 2014; 52:399-413. [PMID: 25186232 DOI: 10.1007/s12035-014-8878-3] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Accepted: 08/25/2014] [Indexed: 01/18/2023]
Abstract
Alzheimer's disease (AD) is a highly heritable disease (with heritability up to 76%) with a complex genetic profile of susceptibility, among which large genome-wide association studies (GWASs) pointed to the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene as a susceptibility locus for late-onset Alzheimer's disease (LOAD) incidence. Here, we summarize the known functions of PICALM and discuss its genetic polymorphisms and their potential physiological effects associated with LOAD. Compelling data indicated that PICALM affects AD risk primarily by modulating production, transportation, and clearance of β-amyloid (Aβ) peptide, but other Aβ-independent pathways are discussed, including tauopathy, synaptic dysfunction, disorganized lipid metabolism, immune disorder, and disrupted iron homeostasis. Finally, given the potential involvement of PICALM in facilitating AD occurrence in multiple ways, it might be possible that targeting PICALM might provide promising and novel avenues for AD therapy.
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Affiliation(s)
- Wei Xu
- Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China
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Wijsman LW, Sabayan B, van Vliet P, Trompet S, de Ruijter W, Poortvliet RKE, van Peet PG, Gussekloo J, Jukema JW, Stott DJ, Sattar N, Ford I, Westendorp RGJ, de Craen AJM, Mooijaart SP. N-terminal pro-brain natriuretic peptide and cognitive decline in older adults at high cardiovascular risk. Ann Neurol 2014; 76:213-22. [DOI: 10.1002/ana.24203] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 06/16/2014] [Accepted: 06/16/2014] [Indexed: 01/21/2023]
Affiliation(s)
- Liselotte W. Wijsman
- Department of Gerontology and Geriatrics; Leiden University Medical Center; Leiden the Netherlands
- Netherlands Consortium for Healthy Ageing; Leiden the Netherlands
| | - Behnam Sabayan
- Department of Gerontology and Geriatrics; Leiden University Medical Center; Leiden the Netherlands
- Department of Radiology; Leiden University Medical Center; Leiden the Netherlands
| | - Peter van Vliet
- Department of Gerontology and Geriatrics; Leiden University Medical Center; Leiden the Netherlands
- Department of Neurology; Leiden University Medical Center; Leiden the Netherlands
| | - Stella Trompet
- Department of Gerontology and Geriatrics; Leiden University Medical Center; Leiden the Netherlands
- Department of Cardiology; Leiden University Medical Center; Leiden the Netherlands
| | - Wouter de Ruijter
- Department of Public Health and Primary Care; Leiden University Medical Center; Leiden the Netherlands
| | | | - Petra G. van Peet
- Department of Public Health and Primary Care; Leiden University Medical Center; Leiden the Netherlands
| | - Jacobijn Gussekloo
- Department of Public Health and Primary Care; Leiden University Medical Center; Leiden the Netherlands
| | - J. Wouter Jukema
- Department of Cardiology; Leiden University Medical Center; Leiden the Netherlands
| | - David J. Stott
- Academic Section of Geriatric Medicine, Faculty of Medicine, University of Glasgow; Glasgow United Kingdom
| | - Naveed Sattar
- British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow; Glasgow United Kingdom
| | - Ian Ford
- Robertson Center for Biostatistics, University of Glasgow; Glasgow United Kingdom
| | | | - Anton J. M. de Craen
- Department of Gerontology and Geriatrics; Leiden University Medical Center; Leiden the Netherlands
- Netherlands Consortium for Healthy Ageing; Leiden the Netherlands
| | - Simon P. Mooijaart
- Department of Gerontology and Geriatrics; Leiden University Medical Center; Leiden the Netherlands
- Netherlands Consortium for Healthy Ageing; Leiden the Netherlands
- Institute for Evidence-Based Medicine in Old Age; Leiden the Netherlands
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