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Ricciardiello A, McKinnon AC, Mowszowski L, LaMonica HM, Schrire ZM, Haroutonian C, Lam A, Hickie IB, D'Rozario A, Naismith SL. Assessing sleep architecture and cognition in older adults with depressive symptoms attending a memory clinic. J Affect Disord 2024; 348:35-43. [PMID: 38123073 DOI: 10.1016/j.jad.2023.12.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 11/28/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND While depression is intrinsically and bidirectionally linked with both sleep disturbance and cognition, the inter-relationships between sleep, cognition, and brain integrity in older people with depression, especially those with late-onset depression are undefined. METHODS One hundred and seventy-two older adults (mean age 64.3 ± 6.9 years, Depression: n = 66, Control: n = 106) attending a memory clinic underwent a neuropsychological battery of declarative memory, executive function tasks, cerebral magnetic resonance imaging and overnight polysomnography with quantitative electroencephalography. RESULTS The time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, slow-wave activity, sleep spindles, hippocampal volume and prefrontal cortex thickness did not differ between depression and control and depression onset groups. However, sleep onset latency (p = 0.005) and REM onset latency (p = 0.02) were later in the Depression group compared to controls. Less SWS was associated with poorer memory (r = 0.31, p = 0.023) in the depression group, and less SWS was related to better memory in the control group (r = -0.20, p = 0.043; Fishers r-to-z = -3.19). LIMITATIONS Longitudinal studies are needed to determine if changes in sleep in those with depressive symptoms predict cognitive decline and illness trajectory. CONCLUSION Older participants with depressive symptoms had delayed sleep initiation, suggestive of delayed sleep phase. The association between SWS and memory suggests SWS may be a useful target for cognitive intervention in older adults with depression symptoms. Reduced hippocampal volumes did not mediate this relationship, indicating a broader distributed neural network may underpin these associations.
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Affiliation(s)
- Andrea Ricciardiello
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia; CIRUS, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Camperdown, NSW, Australia.
| | - Andrew C McKinnon
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia; CogSleep, Australian National Health and Medical Research Council Centre of Research Excellence, Australia
| | - Loren Mowszowski
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia; CogSleep, Australian National Health and Medical Research Council Centre of Research Excellence, Australia
| | - Haley M LaMonica
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
| | - Zoe Menczel Schrire
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia; CIRUS, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Camperdown, NSW, Australia; CogSleep, Australian National Health and Medical Research Council Centre of Research Excellence, Australia
| | - Carla Haroutonian
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia; CIRUS, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Camperdown, NSW, Australia
| | - Aaron Lam
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia; CIRUS, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Camperdown, NSW, Australia; School of Psychological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia
| | - Ian B Hickie
- School of Psychological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia
| | - Angela D'Rozario
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; CIRUS, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Macquarie University, Camperdown, NSW, Australia; CogSleep, Australian National Health and Medical Research Council Centre of Research Excellence, Australia; School of Psychological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia
| | - Sharon L Naismith
- School of Psychology, Faculty of Science, University of Sydney, Camperdown, NSW, Australia; Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia; Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia; CogSleep, Australian National Health and Medical Research Council Centre of Research Excellence, Australia
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Hannon K, Bijsterbosch J. Challenges in Identifying Individualized Brain Biomarkers of Late Life Depression. ADVANCES IN GERIATRIC MEDICINE AND RESEARCH 2024; 5:e230010. [PMID: 38348374 PMCID: PMC10861244 DOI: 10.20900/agmr20230010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
Research into neuroimaging biomarkers for Late Life Depression (LLD) has identified neural correlates of LLD including increased white matter hyperintensities and reduced hippocampal volume. However, studies into neuroimaging biomarkers for LLD largely fail to converge. This lack of replicability is potentially due to challenges linked to construct variability, etiological heterogeneity, and experimental rigor. We discuss suggestions to help address these challenges, including improved construct standardization, increased sample sizes, multimodal approaches to parse heterogeneity, and the use of individualized analytical models.
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Affiliation(s)
- Kayla Hannon
- Department of Radiology, Washington University in St Louis, St Louis MO, 63110, USA
| | - Janine Bijsterbosch
- Department of Radiology, Washington University in St Louis, St Louis MO, 63110, USA
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Barlet BD, Hauson AO, Pollard AA, Zhang EZ, Nemanim NM, Sarkissians S, Lackey NS, Stelmach NP, Walker AD, Carson BT, Flora-Tostado C, Reszegi K, Allen KE, Viglione DJ. Neuropsychological Performance in Alzheimer's Disease versus Late-Life Depression: A Systematic Review and Meta-Analysis. Arch Clin Neuropsychol 2023; 38:991-1016. [PMID: 37332152 DOI: 10.1093/arclin/acad036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2023] [Indexed: 06/20/2023] Open
Abstract
OBJECTIVE Despite decades of research, neuropsychological tests (NPTs) that clearly differentiate between Alzheimer's disease (AD) and late-life depression (LLD) have yet to be agreed upon. Given this gap in knowledge and the rapid deployment of disease-modifying drugs for the two disorders, accurate clinical diagnosis using evidence-based assessment is essential. This study aims to systematically examine the literature to identify NPTs that would be able to differentiate AD and LLD. METHOD Databases and bibliographies were searched to identify articles for analysis. Two major inclusion criteria were that the studies compared neuropsychological functioning of AD versus LLD using normed NPTs and provided data for effect size calculation. Risk of bias was minimized by having independent coders for all steps in the review. RESULTS Forty-one studies met inclusion criteria (N = 2,797) and provided effect sizes for tests that were classified as belonging to 15 domains of functioning. The two groups were well differentiated by tasks of delayed contextual verbal memory as compared to immediate or non-contextual memory, recognition cueing, confrontation naming, visuospatial construction, and conceptualization. Specific NPTs that appear to be useful for differential diagnosis include the Rey Auditory Verbal Learning Test-Delayed Recognition; Boston Naming Test; the Dementia Rating Scale's memory, conceptualization, and construction subscales; and the CERAD Constructional Praxis. CONCLUSIONS The NPTs highlighted in this systematic review could be used as a relatively simple and cost-effective method to differentiate between patients with cognitive dysfunction due to AD versus LLD.
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Affiliation(s)
- Brianna D Barlet
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Alexander O Hauson
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
- Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA
| | - Anna A Pollard
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Emily Z Zhang
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Natasha M Nemanim
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Sharis Sarkissians
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Nick S Lackey
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Nicholas P Stelmach
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Alyssa D Walker
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Bryce T Carson
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Christopher Flora-Tostado
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Katalin Reszegi
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Kenneth E Allen
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
- Institute of Brain Research and Integrated Neuropsychological Services (iBRAINs.org), San Diego, CA 92105, USA
| | - Donald J Viglione
- Clinical Psychology PhD Program, California School of Professional Psychology, San Diego, CA 92131, USA
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Szymkowicz SM, Gerlach AR, Homiack D, Taylor WD. Biological factors influencing depression in later life: role of aging processes and treatment implications. Transl Psychiatry 2023; 13:160. [PMID: 37160884 PMCID: PMC10169845 DOI: 10.1038/s41398-023-02464-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 04/23/2023] [Accepted: 04/27/2023] [Indexed: 05/11/2023] Open
Abstract
Late-life depression occurring in older adults is common, recurrent, and malignant. It is characterized by affective symptoms, but also cognitive decline, medical comorbidity, and physical disability. This behavioral and cognitive presentation results from altered function of discrete functional brain networks and circuits. A wide range of factors across the lifespan contributes to fragility and vulnerability of those networks to dysfunction. In many cases, these factors occur earlier in life and contribute to adolescent or earlier adulthood depressive episodes, where the onset was related to adverse childhood events, maladaptive personality traits, reproductive events, or other factors. Other individuals exhibit a later-life onset characterized by medical comorbidity, pro-inflammatory processes, cerebrovascular disease, or developing neurodegenerative processes. These later-life processes may not only lead to vulnerability to the affective symptoms, but also contribute to the comorbid cognitive and physical symptoms. Importantly, repeated depressive episodes themselves may accelerate the aging process by shifting allostatic processes to dysfunctional states and increasing allostatic load through the hypothalamic-pituitary-adrenal axis and inflammatory processes. Over time, this may accelerate the path of biological aging, leading to greater brain atrophy, cognitive decline, and the development of physical decline and frailty. It is unclear whether successful treatment of depression and avoidance of recurrent episodes would shift biological aging processes back towards a more normative trajectory. However, current antidepressant treatments exhibit good efficacy for older adults, including pharmacotherapy, neuromodulation, and psychotherapy, with recent work in these areas providing new guidance on optimal treatment approaches. Moreover, there is a host of nonpharmacological treatment approaches being examined that take advantage of resiliency factors and decrease vulnerability to depression. Thus, while late-life depression is a recurrent yet highly heterogeneous disorder, better phenotypic characterization provides opportunities to better utilize a range of nonspecific and targeted interventions that can promote recovery, resilience, and maintenance of remission.
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Affiliation(s)
- Sarah M Szymkowicz
- Center for Cognitive Medicine, Department of Psychiatry and Behavioral Science, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Andrew R Gerlach
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Damek Homiack
- Department of Psychiatry, University of Illinois-Chicago, Chicago, IL, USA
| | - Warren D Taylor
- Center for Cognitive Medicine, Department of Psychiatry and Behavioral Science, Vanderbilt University Medical Center, Nashville, TN, USA.
- Geriatric Research, Education, and Clinical Center, Veterans Affairs Tennessee Valley Health System, Nashville, TN, USA.
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Exploration of the Core Pathways and Potential Targets of Luteolin Treatment on Late-Onset Depression Based on Cerebrospinal Fluid Proteomics. Int J Mol Sci 2023; 24:ijms24043485. [PMID: 36834894 PMCID: PMC9958965 DOI: 10.3390/ijms24043485] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/31/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
Cognitive deficiency is one of the fundamental characteristics of late-onset depression (LOD). Luteolin (LUT) possesses antidepressant, anti-aging, and neuroprotective properties, which can dramatically enhance cognition. The altered composition of cerebrospinal fluid (CSF), which is involved in neuronal plasticity and neurogenesis, directly reflects the physio-pathological status of the central nervous system. It is not well known whether the effect of LUT on LOD is in association with a changed CSF composition. Therefore, this study first established a rat model of LOD and then tested the therapeutic effects of LUT using several behavioral approaches. A gene set enrichment analysis (GSEA) was used to evaluate the CSF proteomics data for KEGG pathway enrichment and Gene Ontology annotation. We combined network pharmacology and differentially expressed proteins to screen for key GSEA-KEGG pathways as well as potential targets for LUT therapy for LOD. Molecular docking was adopted to verify the affinity and binding activity of LUT to these potential targets. The outcomes demonstrated that LUT improved the cognitive and depression-like behaviors in LOD rats. LUT may exert therapeutic effects on LOD through the axon guidance pathway. Five axon guidance molecules-EFNA5, EPHB4, EPHA4, SEMA7A, and NTNG-as well as UNC5B, L1CAM, and DCC, may be candidates for the LUT treatment of LOD.
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Lozupone M, Castellana F, Sardone R, Berardino G, Mollica A, Zupo R, De Pergola G, Griseta C, Stallone R, La Montagna M, Dibello V, Seripa D, Daniele A, Altamura M, Solfrizzi V, Bellomo A, Panza F. Late-Onset Depression but not Early-Onset Depression may Increase the Risk of All-Cause Mortality in Older Age: 8-Year Follow-Up of the Salus in Apulia Study. J Am Med Dir Assoc 2022; 24:679-687. [PMID: 36596468 DOI: 10.1016/j.jamda.2022.12.005] [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: 09/20/2022] [Revised: 11/21/2022] [Accepted: 12/01/2022] [Indexed: 01/01/2023]
Abstract
OBJECTIVES Individuals with late-life depression (LLD) may have shorter survival, but there is a lack of findings in population-based settings about health-related outcomes of LLD and its subtypes: early-onset depression (EOD) and late-onset depression (LOD). We aimed to evaluate the risk of all-cause mortality of individuals with LLD and its subtypes in an older population-based cohort. Moreover, we investigated whether inflammatory, cognitive, genetic features and multimorbidity could modify the effect of this association. DESIGN Longitudinal population-based study with 8-year follow-up. SETTING AND PARTICIPANTS We analyzed data on a sample of 1479 participants, all aged >65 years, in the Salus in Apulia Study. METHODS LLD was diagnosed through DSM-IV-TR criteria and LOD and EOD according to the age of onset. Multimorbidity status was defined as the copresence of 2 or more chronic diseases. RESULTS The overall prevalence of LLD in this older sample from Southern Italy was 10.2%, subdivided into 3.4% EOD and 6.8% LOD. In multivariable Cox models adjusted for age, gender, education, global cognition, apolipoprotein E ε4 allele, physical frailty, interleukin-6, and multimorbidity, LLD showed a greater risk of all-cause mortality. LOD differed from EOD regarding gender, education, cognitive dysfunctions, and diabetes mellitus. There was a significantly increased risk of all-cause mortality for participants with LOD (hazard ratio:1.99; 95% CI 1.33-2.97) in the time of observation between enrollment date and death date (7.31 ± 2.17 months). CONCLUSIONS AND IMPLICATION In older age, individuals with LOD but not with EOD had a significantly decreased survival, probably related to increased inflammation, multimorbidity, and cognitive impairments.
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Affiliation(s)
- Madia Lozupone
- Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
| | - Fabio Castellana
- Healthy Aging Phenotypes Research Unit-"Salus in Apulia Study"-National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy
| | - Rodolfo Sardone
- Healthy Aging Phenotypes Research Unit-"Salus in Apulia Study"-National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy
| | - Giuseppe Berardino
- Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy
| | - Anita Mollica
- Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy
| | - Roberta Zupo
- Healthy Aging Phenotypes Research Unit-"Salus in Apulia Study"-National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy
| | - Giovanni De Pergola
- Healthy Aging Phenotypes Research Unit-"Salus in Apulia Study"-National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy
| | - Chiara Griseta
- Healthy Aging Phenotypes Research Unit-"Salus in Apulia Study"-National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy
| | - Roberta Stallone
- Neuroscience and Education, Human Resources Excellence in Research, University of Foggia, Foggia, Italy
| | - Maddalena La Montagna
- Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy
| | - Vittorio Dibello
- Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Davide Seripa
- Hematology and Stem Cell Transplant Unit, "Vito Fazzi" Hospital, Lecce, Italy
| | - Antonio Daniele
- Department of Neuroscience, Catholic University of Sacred Heart, Rome, Italy; Neurology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
| | - Mario Altamura
- Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy
| | - Vincenzo Solfrizzi
- Dipartimento Interdisciplinare di Medicina, Clinica Medica e Geriatria "Cesare Frugoni", University of Bari Aldo Moro, Bari, Italy
| | - Antonello Bellomo
- Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, Italy
| | - Francesco Panza
- Healthy Aging Phenotypes Research Unit-"Salus in Apulia Study"-National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy.
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Yang W, Wang Z, Li X, Qi X, Zhang L, Pan KY, Xu W. Association of depression with mortality in nationwide twins: The mediating role of dementia. Eur Psychiatry 2022; 65:e63. [PMID: 36184891 PMCID: PMC9641650 DOI: 10.1192/j.eurpsy.2022.34] [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: 11/26/2022] Open
Abstract
BACKGROUND The differential impact of depression across different periods in life on mortality remains inconclusive. We aimed to examine the association of depression that occurs at different age with all-cause mortality, and to explore the roles of dementia, as well as genetic and early-life environmental factors, in this association. METHODS From the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression was ascertained using the National Patient Registry and categorized as early-life (<45 years), midlife (45-64 years), and late-life (≥65 years) depression according to the age of the first diagnosis. Deaths were identified through the Cause of Death Register. Generalized estimating equation, generalized structural equation, and conditional logistic regression were used for unmatched, mediation, and co-twin matched analyses, respectively. RESULTS In unmatched analyses, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of mortality were 1.71 (1.46-2.00) for depression at any age, 1.72 (1.36-2.17) for early-life, 1.51 (1.19-1.90) for midlife, and 4.10 (2.02-8.34) for late-life depression. Mortality was significantly higher in individuals with late-life depression than those with earlier-life depression (p < 0.05). The mediation analysis showed that 59.83% of the depression-mortality association was mediated by dementia. No significant difference in ORs between the unmatched and co-twin matched analyses was observed (p = 0.09). CONCLUSIONS Depression is associated with an increased risk of all-cause mortality, and dementia mediates approximately 60% of the impact of depression on mortality in late life. Genetic and early-life environmental factors may not play a significant role in the depression-mortality association.
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Affiliation(s)
- Wenzhe Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China
| | - Zhiyu Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China
| | - Xuerui Li
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China
| | - Xiuying Qi
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China,Authors for correspondence: Xiuying Qi, Weili Xu, E-mails: ;
| | - Lulu Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China
| | - Kuan-Yu Pan
- Department of Psychiatry, Amsterdam Public Health, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands
| | - Weili Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China,Aging Research Center, Department of Neurobiology, Health Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden,Authors for correspondence: Xiuying Qi, Weili Xu, E-mails: ;
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Lee J, Ju G, Park H, Chung S, Son JW, Shin CJ, Lee SI, Kim S. Hippocampal Subfields and White Matter Connectivity in Patients with Subclinical Geriatric Depression. Brain Sci 2022; 12:brainsci12030329. [PMID: 35326285 PMCID: PMC8946804 DOI: 10.3390/brainsci12030329] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/22/2022] [Accepted: 02/24/2022] [Indexed: 02/01/2023] Open
Abstract
Despite an abundance of research related to the functional and structural changes of the brain in patients with geriatric depression, knowledge related to early alterations such as decreased white matter connectivity and their association with cognitive decline remains lacking. We aimed to investigate early alterations in hippocampal microstructure and identify their associations with memory function in geriatric patients with subclinical depression. Nineteen participants with subclinical geriatric depression and 19 healthy controls aged ≥65 years exhibiting general cognitive function within the normal range were included in the study and underwent assessments of verbal memory. Hippocampal subfield volumes were determined based on T1-weighted magnetization-prepared rapid gradient echo (T1-MPRAGE) images, while group tractography and connectometry analyses were conducted using diffusion tensor images. Our findings indicated that the volumes of whole bilateral hippocampus, cornus ammonis (CA) 1, molecular layer, left subiculum, CA3, hippocampal tail, right CA4, and granule cell/molecular layers of the dentate gyrus (GC-ML-DG) were significantly smaller in the subclinical depression group than in the control group. In the subclinical depression group, verbal learning was positively correlated with the volumes of the CA1, GC-ML-DG, molecular layer, and whole hippocampus in the right hemisphere. The fractional anisotropy of the bilateral fornix was also significantly lower in the subclinical depression group and exhibited a positive correlation with verbal learning and recall in both groups. Our results suggest that hippocampal microstructure is disrupted and associated with memory in patients with subclinical depression.
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Affiliation(s)
- Jeonghwan Lee
- Department of Psychiatry, Chungbuk National University Hospital, Cheongju 28644, Korea; (J.L.); (G.J.); (H.P.); (S.C.); (J.-W.S.); (C.-J.S.); (S.I.L.)
- Department of Psychiatry, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Gawon Ju
- Department of Psychiatry, Chungbuk National University Hospital, Cheongju 28644, Korea; (J.L.); (G.J.); (H.P.); (S.C.); (J.-W.S.); (C.-J.S.); (S.I.L.)
- Department of Psychiatry, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Hyemi Park
- Department of Psychiatry, Chungbuk National University Hospital, Cheongju 28644, Korea; (J.L.); (G.J.); (H.P.); (S.C.); (J.-W.S.); (C.-J.S.); (S.I.L.)
- Department of Psychiatry, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Seungwon Chung
- Department of Psychiatry, Chungbuk National University Hospital, Cheongju 28644, Korea; (J.L.); (G.J.); (H.P.); (S.C.); (J.-W.S.); (C.-J.S.); (S.I.L.)
- Department of Psychiatry, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Jung-Woo Son
- Department of Psychiatry, Chungbuk National University Hospital, Cheongju 28644, Korea; (J.L.); (G.J.); (H.P.); (S.C.); (J.-W.S.); (C.-J.S.); (S.I.L.)
- Department of Psychiatry, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Chul-Jin Shin
- Department of Psychiatry, Chungbuk National University Hospital, Cheongju 28644, Korea; (J.L.); (G.J.); (H.P.); (S.C.); (J.-W.S.); (C.-J.S.); (S.I.L.)
- Department of Psychiatry, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Sang Ick Lee
- Department of Psychiatry, Chungbuk National University Hospital, Cheongju 28644, Korea; (J.L.); (G.J.); (H.P.); (S.C.); (J.-W.S.); (C.-J.S.); (S.I.L.)
- Department of Psychiatry, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Siekyeong Kim
- Department of Psychiatry, Chungbuk National University Hospital, Cheongju 28644, Korea; (J.L.); (G.J.); (H.P.); (S.C.); (J.-W.S.); (C.-J.S.); (S.I.L.)
- Department of Psychiatry, College of Medicine, Chungbuk National University, Cheongju 28644, Korea
- Correspondence: ; Tel.: +82-43-269-6364; Fax: +82-43-267-7951
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9
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Moazzami K, Wittbrodt MT, Lima BB, Kim JH, Hammadah M, Ko YA, Obideen M, Abdelhadi N, Kaseer B, Gafeer MM, Nye JA, Shah AJ, Ward L, Raggi P, Waller EK, Bremner JD, Quyyumi AA, Vaccarino V. Circulating Progenitor Cells and Cognitive Impairment in Men and Women with Coronary Artery Disease. J Alzheimers Dis 2021; 74:659-668. [PMID: 32083582 DOI: 10.3233/jad-191063] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Circulating progenitor cells (CPC) have been associated with memory function and cognitive impairment in healthy adults. However, it is unclear whether such associations also exist in patients with coronary artery disease (CAD). OBJECTIVE To assess the association between CPCs and memory performance among individuals with CAD. METHODS We assessed cognitive function in 509 patients with CAD using the verbal and visual Memory subtests of the Wechsler memory scale-IV and the Trail Making Test parts A and B. CPCs were enumerated with flow cytometry as CD45med/CD34+ blood mononuclear cells, those co-expressing other epitopes representing populations enriched for hematopoietic and endothelial progenitors. RESULTS After adjusting for demographic and cardiovascular risk factors, lower number of endothelial progenitor cell counts were independently associated with lower visual and verbal memory scores (p for all < 0.05). There was a significant interaction in the magnitude of this association with race (p < 0.01), such that the association of verbal memory scores with endothelial progenitor subsets was present in Black but not in non-Black participants. No associations were present with the hematopoietic progenitor-enriched cells or with the Trail Making Tests. CONCLUSION Lower numbers of circulating endothelial progenitor cells are associated with cognitive impairment in patients with CAD, suggesting a protective effect of repair/regeneration processes in the maintenance of cognitive status. Impairment of verbal memory function was more strongly associated with lower CPC counts in Black compared to non-Black participants with CAD. Whether strategies designed to improve regenerative capacity will improve cognition needs further study.
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Affiliation(s)
- Kasra Moazzami
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Matthew T Wittbrodt
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Bruno B Lima
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Jeong Hwan Kim
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Muhammad Hammadah
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Yi-An Ko
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Malik Obideen
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Naser Abdelhadi
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Belal Kaseer
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - M Mazen Gafeer
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Jonathon A Nye
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Amit J Shah
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.,Atlanta VA Medical Center, Decatur, GA, USA
| | - Laura Ward
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Paolo Raggi
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Mazankowski Alberta Heart Institute, University of Alberta, Alberta, Canada
| | - Edmund K Waller
- Department of Hematology and Oncology, Winship Cancer Institute, Atlanta, GA, USA
| | - J Douglas Bremner
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.,Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA.,Atlanta VA Medical Center, Decatur, GA, USA
| | - Arshed A Quyyumi
- Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Viola Vaccarino
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.,Department of Medicine, Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
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10
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Siddarth P, Funes CM, Laird KT, Ercoli L, Lavretsky H. Predictors of Cognitive Improvement Following Treatment for Late-Life Depression. J Geriatr Psychiatry Neurol 2021; 34:162-168. [PMID: 32208884 DOI: 10.1177/0891988720915515] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Cognitive impairment is frequently comorbid with late-life depression (LLD) and often persists despite remission of mood symptoms with antidepressant treatment. Increasing understanding of factors that predict improvement of cognitive symptoms in LLD is useful to inform treatment recommendations. METHODS We used data from 2 randomized clinical trials of geriatric depression to examine the relationships between sociodemographic factors (resilience, quality of life) and clinical factors (age of depression onset, severity of depression, apathy) with subsequent cognitive outcomes. One hundred sixty-five older adults with major depression who had completed one of 2 clinical trials were included: (1) methylphenidate plus placebo, citalopram plus placebo, and citalopram plus methylphenidate or (2) citalopram combined with Tai Chi or health education. A comprehensive neuropsychiatric battery was administered; 2 measures of cognitive improvement were examined, one defined as an increase in general cognitive performance score of at least 1 standard deviation and the other 0.5 standard deviation pre-post treatment. RESULTS At posttreatment, 59% of participants had remitted, but less than a third of those who remitted showed cognitive improvement (29%). Cognitive improvement was observed in 18% of nonremitters. Lower baseline depression severity, greater social functioning, and depression onset prior to 60 years of age were significantly associated with cognitive improvement. None of the other measures, including baseline apathy, resilience, and depression remission status, were significantly associated with cognitive improvement. CONCLUSIONS Lower severity of depression, earlier onset, and greater social functioning may predict improvement in cognitive functioning with treatment for depression in LLD.
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Affiliation(s)
- Prabha Siddarth
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at 8783UCLA, Los Angeles, CA, USA
| | - Cynthia M Funes
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at 8783UCLA, Los Angeles, CA, USA.,Neuroscience Institute, Banner University Medical Center Phoenix, University of Arizona College of Medicine, Phoenix, AZ, USA
| | - Kelsey T Laird
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at 8783UCLA, Los Angeles, CA, USA
| | - Linda Ercoli
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at 8783UCLA, Los Angeles, CA, USA
| | - Helen Lavretsky
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at 8783UCLA, Los Angeles, CA, USA
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11
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Piers RJ, Liu Y, Ang TF, Tao Q, Au R, Qiu WQ. Association Between Elevated Depressive Symptoms and Cognitive Function Moderated by APOE4 Status: Framingham Offspring Study. J Alzheimers Dis 2021; 80:1269-1279. [PMID: 33646152 PMCID: PMC8172078 DOI: 10.3233/jad-200998] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Depression and Apolipoprotein E4 (APOE4) are associated with decreased cognitive function and differences in brain structure. OBJECTIVE This study investigated whether APOE4 status moderates the association between elevated depressive symptoms, cognitive function, and brain structure. METHODS Stroke- and dementia-free participants (n = 1,968) underwent neuropsychological evaluation, brain MRI, and depression screening. Linear and logistic regression was used to examine all associations. Secondary analyses were performed using interaction terms to assess effect modification by APOE4 status. RESULTS Elevated depressive symptoms were associated with lower cognitive performance in several domains. In stratified analyses, elevated depressive symptoms were associated with poorer visual short- and long-term memory performance for APOE4 + participants. Elevated depressive symptoms were not associated with any brain structure in this study sample. CONCLUSION Elevated depressive symptoms impact cognitive function in non-demented individuals. Having the APOE4 allele may exacerbate the deleterious effects of elevated depressive symptoms on visual memory performance. Screening for elevated depressive symptoms in both research studies and clinical practice may be warranted to avoid false positive identification of neurodegeneration, particularly among those who are APOE4 + .
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Affiliation(s)
- Ryan J. Piers
- Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
| | - Yulin Liu
- The Framingham Heart Study, Boston University School of Medicine, Boston, MA, USA
- Department of Neurology, Boston University School of Medicine, Boston, MA, USA
| | - Ting F.A. Ang
- The Framingham Heart Study, Boston University School of Medicine, Boston, MA, USA
- Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA
| | - Qiushan Tao
- Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA
| | - Rhoda Au
- The Framingham Heart Study, Boston University School of Medicine, Boston, MA, USA
- Department of Neurology, Boston University School of Medicine, Boston, MA, USA
- Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA
- Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
- Alzheimer’s Disease Center, Boston University School of Medicine, Boston, MA, USA
| | - Wendy Q. Qiu
- Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA
- Alzheimer’s Disease Center, Boston University School of Medicine, Boston, MA, USA
- Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA
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12
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Comparison of cognitive function between early- and late-onset late-life depression in remission. Psychiatry Res 2020; 290:113051. [PMID: 32474065 DOI: 10.1016/j.psychres.2020.113051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 03/05/2020] [Accepted: 04/28/2020] [Indexed: 12/21/2022]
Abstract
Differences in cognitive function have been suggested in people with late-life depression between those with early- (EOD) and late-onset (LOD), possibly reflecting different etiologies. The cutoff point for EOD and LOD was the first depressive episode before age 60 or later. However, depressive symptoms at the time of disorder are important confounders. The study aimed to compare cognitive function in older people with EOD and LOD in the euthymic state. A sample of 135 participants aged 60+ with a history of major depressive disorder in remission, received neuropsychological evaluation including tests of memory, attention, processing speed, visuospatial function, language, and executive function. Individual test scores and a derived composite score were investigated as dependent variables against age of onset using multiple linear regressions adjusted for potential confounders, including residual depressive symptoms. We found EOD (N = 67) and LOD (N = 68) groups did not differ significantly in overall composite cognitive scores after adjustment. Of individual test scores, only those for immediate recall were significantly lower in participants with EOD compared to LOD. In conclusion, the study found no associations between cognitive function and age of onset in this sample of people with depressive disorder in remission. Active or residual depressive symptoms might have confounded this relationship in previous research.
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13
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Rushia SN, Shehab AAS, Motter JN, Egglefield DA, Schiff S, Sneed JR, Garcon E. Vascular depression for radiology: A review of the construct, methodology, and diagnosis. World J Radiol 2020; 12:48-67. [PMID: 32549954 PMCID: PMC7288775 DOI: 10.4329/wjr.v12.i5.48] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 05/05/2020] [Accepted: 05/12/2020] [Indexed: 02/06/2023] Open
Abstract
Vascular depression (VD) as defined by magnetic resonance imaging (MRI) has been proposed as a unique subtype of late-life depression. The VD hypothesis posits that cerebrovascular disease, as characterized by the presence of MRI-defined white matter hyperintensities, contributes to and increases the risk for depression in older adults. VD is also accompanied by cognitive impairment and poor antidepressant treatment response. The VD diagnosis relies on MRI findings and yet this clinical entity is largely unfamiliar to neuroradiologists and is rarely, if ever, discussed in radiology journals. The primary purpose of this review is to introduce the MRI-defined VD construct to the neuroradiology community. Case reports are highlighted in order to illustrate the profile of VD in terms of radiological, clinical, and neuropsychological findings. A secondary purpose is to elucidate and elaborate on the measurement of cerebrovascular disease through visual rating scales and semi- and fully-automated volumetric methods. These methods are crucial for determining whether lesion burden or lesion severity is the dominant pathological contributor to VD. Additionally, these rating methods have implications for the growing field of computer assisted diagnosis. Since VD has been found to have a profile that is distinct from other types of late-life depression, neuroradiologists, in conjunction with psychiatrists and psychologists, should consider VD in diagnosis and treatment planning.
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Affiliation(s)
- Sara N Rushia
- Department of Psychology, The Graduate Center, City University of New York, New York, NY 10016, United States
- Department of Psychology, Queens College, City University of New York, Queens, NY 11367, United States
| | - Al Amira Safa Shehab
- Department of Psychology, The Graduate Center, City University of New York, New York, NY 10016, United States
- Department of Psychology, Queens College, City University of New York, Queens, NY 11367, United States
| | - Jeffrey N Motter
- Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, NY 10032, United States
- Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, United States
| | - Dakota A Egglefield
- Department of Psychology, The Graduate Center, City University of New York, New York, NY 10016, United States
- Department of Psychology, Queens College, City University of New York, Queens, NY 11367, United States
| | - Sophie Schiff
- Department of Psychology, The Graduate Center, City University of New York, New York, NY 10016, United States
- Department of Psychology, Queens College, City University of New York, Queens, NY 11367, United States
| | - Joel R Sneed
- Department of Psychology, The Graduate Center, City University of New York, New York, NY 10016, United States
- Department of Psychology, Queens College, City University of New York, Queens, NY 11367, United States
- Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, NY 10032, United States
- Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, United States
| | - Ernst Garcon
- Department of Radiology, Columbia University Medical Center, New York, NY 10032, United States
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14
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Adler G, Chwalek K, Jajcevic A. Six-month course of mild cognitive impairment and affective symptoms in late-life depression. Eur Psychiatry 2020; 19:502-5. [PMID: 15589711 DOI: 10.1016/j.eurpsy.2004.09.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2003] [Revised: 04/05/2004] [Accepted: 08/25/2004] [Indexed: 11/30/2022] Open
Abstract
AbstractMild cognitive impairment (MCI) is frequent in patients with late-life depression. Previous studies indicate that cognitive performance in these patients is not or only marginally improved when they recover from depression. However, recovery from cognitive impairments due to depression may have a longer time course than recovery from affective symptoms. In a group of 34 elderly depressed patients (mean age: 73.4 years) admitted to a gerontopsychiatric day-clinic, severity of depression and cognitive performance were assessed before the initiation of treatment and were reassessed 6 months later. At admission, 18 of 34 patients (53%) fulfilled the criteria for MCI, with a preponderance of impairments in short-term memory and visuospatial capabilities. At the 6-month follow-up, cognitive performance had not significantly improved for the entire group; 12 of 27 patients (44%) still were fulfilling the criteria for MCI. No relationships could be ascertained between cognitive impairment or functional level and severity or course of depression. Patients with diurnal variations of the depressive symptomatology were less likely to fully recover from depression.
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Affiliation(s)
- Georg Adler
- Altentagesklinik, Zentralinstitut für Seelische Gesundheit, J5, 68159 Mannheim, Germany.
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15
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Gruenbaum BF, Kutz R, Zlotnik A, Boyko M. Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-stroke depression. Ther Adv Psychopharmacol 2020; 10:2045125320903951. [PMID: 32110376 PMCID: PMC7026819 DOI: 10.1177/2045125320903951] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 12/31/2019] [Indexed: 12/16/2022] Open
Abstract
Post-stroke depression (PSD) is a major complication of stroke that significantly impacts functional recovery and quality of life. While the exact mechanism of PSD is unknown, recent attention has focused on the association of the glutamatergic system in its etiology and treatment. Minimizing secondary brain damage and neuropsychiatric consequences associated with excess glutamate concentrations is a vital part of stroke management. The blood glutamate scavengers, oxaloacetate and pyruvate, degrade glutamate in the blood to its inactive metabolite, 2-ketoglutarate, by the coenzymes glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT), respectively. This reduction in blood glutamate concentrations leads to a subsequent shift of glutamate down its concentration gradient from the blood to the brain, thereby decreasing brain glutamate levels. Although there are not yet any human trials that support blood glutamate scavengers for clinical use, there is increasing evidence from animal research of their efficacy as a promising new therapeutic approach for PSD. In this review, we present recent evidence in the literature of the potential therapeutic benefits of blood glutamate scavengers for reducing PSD and other related neuropsychiatric conditions. The evidence reviewed here should be useful in guiding future clinical trials.
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Affiliation(s)
- Benjamin F Gruenbaum
- Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA
| | - Ruslan Kutz
- Division of Anesthesiology and Critical Care, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Alexander Zlotnik
- Division of Anesthesiology and Critical Care, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Matthew Boyko
- Division of Anesthesiology and Critical Care, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel
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16
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Abstract
This article covers current research on the relationship between depression and cognitive impairment in older adults. First, it approaches the clinical assessment of late-life depression and comorbid cognitive impairment. Cognitive risk factors for suicide are discussed. Research is then provided on neuropsychological changes associated with depression, discussing subjective cognitive impairment, mild cognitive impairment, and dementia profiles. In addition, literature regarding neuroimaging and biomarker findings in depressed older adults is presented. Finally, therapeutic models for treatment of late-life depression are discussed, including psychotherapy models, holistic treatments, pharmacologic approaches, and brain stimulation therapies.
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Affiliation(s)
- Ryan D Greene
- Department of Psychology in Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA; Roudebush VA Medical Center, Indianapolis, IN, USA; University of Indianapolis, Indianapolis, IN, USA.
| | - Alex Cook
- University of Indianapolis, Indianapolis, IN, USA
| | - Dustin Nowaskie
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Sophia Wang
- Roudebush VA Medical Center, Indianapolis, IN, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA; Center of Health Innovation and Implementation Science, Center for Translational Science and Innovation, Indianapolis, IN, USA; Sandra Eskenazi Center for Brain Care Innovation, Eskenazi Hospital, Indianapolis, IN, USA
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17
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Borda MG, Santacruz JM, Aarsland D, Camargo-Casas S, Cano-Gutierrez CA, Suárez-Monsalve S, Campos-Fajardo S, Pérez-Zepeda MU. ASSOCIATION OF DEPRESSIVE SYMPTOMS AND SUBJECTIVE MEMORY COMPLAINTS WITH THE INCIDENCE OF COGNITIVE IMPAIRMENT IN OLDER ADULTS WITH HIGH BLOOD PRESSURE. Eur Geriatr Med 2019; 10:413-420. [PMID: 31186819 PMCID: PMC6557430 DOI: 10.1007/s41999-019-00185-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Accepted: 03/22/2019] [Indexed: 01/22/2023]
Abstract
PURPOSE High blood pressure is a relevant risk factor for vascular damage, leading to development of depressive symptoms and dementia in older adults. Moreover, subjective memory complaints are recognized as an early marker of cognitive impairment. However, it has been established that subjective memory complaints could also be a reflection of depressive symptoms. The objective of this paper is to assess the impact of depressive symptoms and subjective memory complaints on the incidence of cognitive impairment in older adults with high blood pressure. METHODS This is a secondary analysis of the Mexican Health and Aging Study, a representative cohort composed by individuals aged ≥ 50 years. Participants with cognitive impairment in 2012 were excluded since the outcome was incident cognitive impairment in 2015. Four groups were created according to depressive symptomatology and subjective memory complaints status, analyses were stratified according to blood pressure status. The odds incident cognitive impairment was estimated through logistic regression models. RESULTS A total of 6,327 participants were included, from which 6.44% developed cognitive impairment. No differences were seen regarding the development of cognitive impairment in participants without high blood pressure. However, increased risk was evident in those with both high blood pressure and depressive symptoms (OR=2.1, 95% CI 1.09 - 4.09, p =0.026) as with high blood pressure, depressive symptoms and subjective memory complaints (OR=1.91, 9% CI 1.4 - 3.2, p= 0.001). CONCLUSION Individuals with high blood pressure have a higher risk of developing incident cognitive impairment when depressive symptoms and/or subjective memory complaints are present. Our results suggest that a sequence of events related to altered cerebral vascular dynamics is possible.
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Affiliation(s)
- Miguel Germán Borda
- Centre for Age-Related Medicine (SESAM), Stavanger University Hospital. Stavanger, Norway
- Semillero de Neurociencias y Envejecimiento, Ageing Institute, Medical School, Pontificia Universidad Javeriana. Bogotá, Colombia
- Faculty of Health Sciences, University of Stavanger, Stavanger, Norway
| | - José Manuel Santacruz
- Cognition and Memory Center, Intellectus. Hospital Universitario San Ignacio. Bogotá Colombia
- Psychiatry Department, Hospital Universitario San Ignacio. Bogotá, Colombia
| | - Dag Aarsland
- Centre for Age-Related Medicine (SESAM), Stavanger University Hospital. Stavanger, Norway
- Department of Old Age Psychiatry, King’s College. London, United Kingdom
| | - Sandy Camargo-Casas
- Semillero de Neurociencias y Envejecimiento, Ageing Institute, Medical School, Pontificia Universidad Javeriana. Bogotá, Colombia
| | - Carlos Alberto Cano-Gutierrez
- Semillero de Neurociencias y Envejecimiento, Ageing Institute, Medical School, Pontificia Universidad Javeriana. Bogotá, Colombia
- Geriatrics Unit, Internal Medicine Department, Hospital Universitario San Ignacio. Bogotá, Colombia
| | - Silvia Suárez-Monsalve
- Semillero de Neurociencias y Envejecimiento, Ageing Institute, Medical School, Pontificia Universidad Javeriana. Bogotá, Colombia
| | - Santiago Campos-Fajardo
- Semillero de Neurociencias y Envejecimiento, Ageing Institute, Medical School, Pontificia Universidad Javeriana. Bogotá, Colombia
| | - Mario Ulises Pérez-Zepeda
- Semillero de Neurociencias y Envejecimiento, Ageing Institute, Medical School, Pontificia Universidad Javeriana. Bogotá, Colombia
- Geriatric Epidemiology Research Department, Instituto Nacional De Geriatría. Mexico D.F, Mexico
- Geriatric Medicine Research Unit, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
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18
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Jamieson A, Goodwill AM, Termine M, Campbell S, Szoeke C. Depression related cerebral pathology and its relationship with cognitive functioning: A systematic review. J Affect Disord 2019; 250:410-418. [PMID: 30878653 DOI: 10.1016/j.jad.2019.03.042] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 02/26/2019] [Accepted: 03/04/2019] [Indexed: 01/29/2023]
Abstract
BACKGROUND Depression's relationship with cerebral abnormalities and cognitive decline is temporally dynamic. Despite clear clinical utility, understanding depression's effect on cerebral structures, cognitive impairment and the interaction between these symptoms has had limited consideration. METHODS This review summarised studies examining a clinical depression diagnosis or validated scales measuring depressive symptoms, data concerning amyloid-beta (Aβ) levels, brain structure and function focusing on hippocampal alterations, or white matter hyperintensities (WMH), and at least one validated neuropsychological test. Online database searches of: PsycINFO, EMBASE, MEDLINE, and Scopus were conducted to identify potential articles. RESULTS While depression was consistently associated with cross-sectionally cognitive decline across multiple domains, the neuropathological basis of this dysfunction remained unclear. Hippocampal, frontal, and limbic dysfunction as well as cortical thinning, WMH, and Aβ burden all provide inconsistent findings, likely due to depression subtypes. The consistency of these findings additionally decreases when examining this relationship longitudinally, as these results are further confounded by pre-dementia states. The therapeutic interventions examined were more efficacious in the younger compared with the older samples, who were characterised by greater WMH and Aβ burden. LIMITATIONS The limited number of longitudinal and interventional studies in addition to the heterogeneity of the samples restricts their generalisability. CONCLUSIONS Symptomatological differences between early-onset and late-onset depression (EOD and LOD) appear crucial in understanding whether late-life depression is the primary or secondary source of cerebral pathology. Though severe cognitive impairments and clearer neuropathological underpinnings are more characteristic of LOD than EOD, the inconsistency of valid biomarkers remains problematic.
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Affiliation(s)
- Alec Jamieson
- Centre for Medical Research, Royal Melbourne Hospital, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Alicia M Goodwill
- Centre for Medical Research, Royal Melbourne Hospital, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia; Healthy Brain Initiative, Faculty of Health Sciences, Australian Catholic University, Melbourne, Victoria, Australia
| | - Mario Termine
- Centre for Medical Research, Royal Melbourne Hospital, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Stephen Campbell
- Australian Healthy Ageing Organisation (AHAO), Parkville, Victoria, Australia
| | - Cassandra Szoeke
- Centre for Medical Research, Royal Melbourne Hospital, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia; Healthy Brain Initiative, Faculty of Health Sciences, Australian Catholic University, Melbourne, Victoria, Australia; Australian Healthy Ageing Organisation (AHAO), Parkville, Victoria, Australia.
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19
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Wang Z, Yuan Y, You J, Zhang Z. Disrupted structural brain connectome underlying the cognitive deficits in remitted late-onset depression. Brain Imaging Behav 2019; 14:1600-1611. [DOI: 10.1007/s11682-019-00091-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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20
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Laird KT, Krause B, Funes C, Lavretsky H. Psychobiological factors of resilience and depression in late life. Transl Psychiatry 2019; 9:88. [PMID: 30765686 PMCID: PMC6375932 DOI: 10.1038/s41398-019-0424-7] [Citation(s) in RCA: 125] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 12/28/2018] [Accepted: 01/26/2019] [Indexed: 12/18/2022] Open
Abstract
In contrast to traditional perspectives of resilience as a stable, trait-like characteristic, resilience is now recognized as a multidimentional, dynamic capacity influenced by life-long interactions between internal and environmental resources. We review psychosocial and neurobiological factors associated with resilience to late-life depression (LLD). Recent research has identified both psychosocial characteristics associated with elevated LLD risk (e.g., insecure attachment, neuroticism) and psychosocial processes that may be useful intervention targets (e.g., self-efficacy, sense of purpose, coping behaviors, social support). Psychobiological factors include a variety of endocrine, genetic, inflammatory, metabolic, neural, and cardiovascular processes that bidirectionally interact to affect risk for LLD onset and course of illness. Several resilience-enhancing intervention modalities show promise for the prevention and treatment of LLD, including cognitive/psychological or mind-body (positive psychology; psychotherapy; heart rate variability biofeedback; meditation), movement-based (aerobic exercise; yoga; tai chi), and biological approaches (pharmacotherapy, electroconvulsive therapy). Additional research is needed to further elucidate psychosocial and biological factors that affect risk and course of LLD. In addition, research to identify psychobiological factors predicting differential treatment response to various interventions will be essential to the development of more individualized and effective approaches to the prevention and treatment of LLD.
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Affiliation(s)
- Kelsey T Laird
- Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA
| | - Beatrix Krause
- Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA
| | - Cynthia Funes
- Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA
| | - Helen Lavretsky
- Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA.
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21
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Bae KY, Kang HJ, Kim JW, Kim SW, Kim JT, Park MS, Cho KH, Kim JM. Associations of white matter hyperintensities with poststroke depression: A 1-year longitudinal study. Int J Geriatr Psychiatry 2019; 34:162-168. [PMID: 30251444 DOI: 10.1002/gps.5005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 09/03/2018] [Indexed: 11/06/2022]
Abstract
BACKGROUND Depression is common in stroke survivors and may lead to a poor prognosis and more severe functional impairment. Although subcortical white matter hyperintensities (WMHs) are associated with late-life depression, few studies have examined the association between depression and WMHs after a stroke. We investigated the associations of periventricular (PVWMH) and deep (DWMH) WMHs with poststroke depression (PSD) at two time points after stroke. METHODS A total of 408 patients were evaluated 2 weeks after stroke (baseline), and of those, 284 (70%) were followed up 1 year later. Magnetic resonance images were obtained in all subjects at baseline. PVWMHs and DWMHs were rated using the four-point modified Fazekas scale and categorized as mild (grades 0 and 1) or severe (grades 2 and 3). Depression was diagnosed according to DSM-IV criteria, and subjects were divided into without PSD, any PSD, and major PSD groups at baseline, and follow-up examinations were conducted according to the severity of depression. Associations of PSD with PVWMHs and DWMHs were assessed using multivariate logistic regression analyses after adjusting for various demographic and clinical characteristics. RESULTS The adjusted analyses revealed that severe PVWMHs were significantly associated with any PSD at baseline and severe DWMHs were significantly associated with major PSD at follow-up. CONCLUSION The association between WMH and PSD varies according to type of WMH, and time after stroke, such that early depressive symptoms are associated with PVWMHs, and delayed severe depression is associated with DWMHs.
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Affiliation(s)
- Kyung-Yeol Bae
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Hee-Ju Kang
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Ju-Wan Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Sung-Wan Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Joon-Tae Kim
- Department of Neurology, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Man-Seok Park
- Department of Neurology, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Ki-Hyun Cho
- Department of Neurology, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Jae-Min Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
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22
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Eraydin IE, Mueller C, Corbett A, Ballard C, Brooker H, Wesnes K, Aarsland D, Huntley J. Investigating the relationship between age of onset of depressive disorder and cognitive function. Int J Geriatr Psychiatry 2019; 34:38-46. [PMID: 30259558 DOI: 10.1002/gps.4979] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 08/06/2018] [Indexed: 11/06/2022]
Abstract
OBJECTIVES Depressive disorder is commonly associated with impaired cognitive function; however, it is unclear whether the age of onset of the first episode of depression, current depression severity, or historical severity of depressive episodes are associated with cognitive performance. METHODS This study examined baseline cross-sectional data from the ongoing online PROTECT study. A total of 7344 participants, 50 years or older, with a history of depression and no diagnosis of dementia were divided into three groups according to age of onset of their first depressive episode: early-onset, midlife-onset, and late-onset. Performance on measures of visuospatial episodic memory, executive function, verbal working, and visual working memory were evaluated. Demographic and clinical characteristics such as age, education, and severity of symptoms during their worst previous depressive episode and current depression severity were included in multivariate regression models. RESULTS The late-onset depression group scored significantly lower on the verbal reasoning task than the early-onset group while there were no significant differences found on the other tasks. Midlife-onset depression participants performed better in the visual episodic memory task, but worse on the verbal reasoning task, than early-onset depression participants. Current depression severity was negatively correlated with all four cognitive domains, while historical severity score was found to be significantly associated with cognitive performance on the verbal reasoning and spatial working memory tasks. CONCLUSIONS The most important indicator of cognitive performance in depression appears to be current, rather than historic depression severity; however, late-onset depression may be associated with more executive impairment than an early-onset depression.
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Affiliation(s)
- Irem Ece Eraydin
- Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Christoph Mueller
- Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | | | | | | | | | - Dag Aarsland
- Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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Abstract
This article covers current research on the relationship between depression and cognitive impairment in older adults. First, it approaches the clinical assessment of late-life depression and comorbid cognitive impairment. Cognitive risk factors for suicide are discussed. Research is then provided on neuropsychological changes associated with depression, discussing subjective cognitive impairment, mild cognitive impairment, and dementia profiles. Additionally, literature regarding neuroimaging and biomarker findings in depressed older adults is presented. Finally, therapeutic models for treatment of late-life depression are also discussed, including psychotherapy models, holistic treatments, pharmacologic approaches, and brain-stimulation therapies.
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WANG J, LI W, YUE L, HONG B, AN N, LI G, XIAO S. The Study of White Matter Hyperintensity (WMH) and Factors Related to Geriatric Late-Onset Depression. SHANGHAI ARCHIVES OF PSYCHIATRY 2018; 30:12-19. [PMID: 29719354 PMCID: PMC5925594 DOI: 10.11919/j.issn.1002-0829.217038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Geriatric depression is one of the most common and harmful mental illnesses seen in the elderly. However, there are few studies focusing on the relationship between late-onset depression (LOD) and social and psychological factors, as well as brain structure. AIMS To explore factors related to late-onset depression (LOD) in elderly patients. METHODS 24 first onset LOD patients over 60 years old (meeting ICD-10 diagnostic criteria for depression) and 23 non-depressed elders were selected for inclusion into this study. Scale assessments, including Fazelasscale for white matter hyperintensity (WMH) high signal level and the MTA-scale for medial temporal lobe atrophy levels, were combined with general demography and sociology data to find factors related to LOD. RESULTS There was no significant difference in age (t=0.419, p=0.678), gender (X2=1.705, p=0.244), or years of education (t=1.478, p=0.146) between the two groups. However, statistical differences were shown on scores on the WMH, (X2=7.817, p=0.008), periventricular white matter hyperintensity (PWMH)(Fisher exact test: p=0.031), having or not having religious beliefs (Fisher exact test: p=0.265) and family harmony (yes or no) (Fisher exact test: p=0.253) between the LOD group and control group. The results of linear regression analysis showed that the total score for WMH, religious beliefs (with or without) and family harmony (yes or no) were associated with depressive symptomology. CONCLUSION Scores on the WMH, religious beliefs and family harmony are all potentially related to LOD in elderly patients.
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Affiliation(s)
| | | | | | | | | | - Guanjun LI
- Alzheimer’s Disease and Related Disorders Center of the Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shifu XIAO
- Alzheimer’s Disease and Related Disorders Center of the Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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25
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Yang WI, Kim IJ, Kim MS, Kim SH, Moon JY, Sung JH, Lim SW, Cha DH, Cho SY. Association of elevated blood pressure during exercise with cerebral white matter lesions. Blood Press 2018; 27:166-172. [PMID: 29308930 DOI: 10.1080/08037051.2018.1423544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVES Cerebral white matter lesions (WMLs) are regarded to be subclinical ischemic changes of the cerebral parenchyma. Many previous studies have shown that baseline blood pressure (BP) is one of the most important factors for WMLs, but the relation between exercise BP and WMLs has not been fully evaluated. So, we sought to investigate the relationships between cerebral WMLs and peak exercise BP. METHODS Brain magnetic resonance imaging scan and treadmill testing were performed simultaneously in 130 consecutive subjects without history of stroke or transient ischemic stroke. RESULTS Among 130 subjects, 42 individuals (32%) presented WMLs. Individuals with WMLs were older than those without WMLs, and baseline systolic BP and pulse pressure were higher in subjects with WMLs. During treadmill test, peak exercise systolic BP was more significantly elevated in subjects with WMLs. In multivariable logistic regression analysis, elevated baseline systolic BP, not peak exercise systolic BP, was associated with the presence of WMLs, independently of age. However, in multivariable logistic regression analysis of 88 normotensive subjects, elevated peak systolic BP during exercise was the only determinant for the presence of WMLs. CONCLUSIONS Elevated peak systolic BP during exercise is significantly related with WMLs, subclinical small vessel disease of brain, especially in normotensive subjects.
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Affiliation(s)
- Woo-In Yang
- a Department of Cardiology , CHA Bundang Medical Center, CHA University , Sungnam , Republic of Korea
| | - In-Jai Kim
- a Department of Cardiology , CHA Bundang Medical Center, CHA University , Sungnam , Republic of Korea
| | - Mi-Sun Kim
- b Department of Radiology , Chaum Medical Center, CHA University , Seoul , Republic of Korea
| | - Sang-Hoon Kim
- a Department of Cardiology , CHA Bundang Medical Center, CHA University , Sungnam , Republic of Korea
| | - Jae-Youn Moon
- a Department of Cardiology , CHA Bundang Medical Center, CHA University , Sungnam , Republic of Korea
| | - Jung-Hoon Sung
- a Department of Cardiology , CHA Bundang Medical Center, CHA University , Sungnam , Republic of Korea
| | - Sang-Wook Lim
- a Department of Cardiology , CHA Bundang Medical Center, CHA University , Sungnam , Republic of Korea
| | - Dong-Hoon Cha
- a Department of Cardiology , CHA Bundang Medical Center, CHA University , Sungnam , Republic of Korea
| | - Seung-Yun Cho
- c Department of Cardiology , Chaum Medical Center, CHA University , Seoul , Republic of Korea
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26
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Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression. Am J Geriatr Psychiatry 2017; 25:1123-1134. [PMID: 28479153 PMCID: PMC5600662 DOI: 10.1016/j.jagp.2017.03.016] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 11/15/2016] [Accepted: 03/24/2017] [Indexed: 01/24/2023]
Abstract
OBJECTIVE Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined. METHODS In a longitudinal study of late-life depression in an academic center, 273 depressed and 164 never-depressed community-dwelling elders aged 60 years or older were followed on average for over 5 years. Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function. RESULTS Depressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3 and 12 month exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. Three-month remitters also exhibited a greater decline in verbal fluency and executive function, whereas 12-month nonremitters exhibited greater decline in executive function than other groups. CONCLUSION Consistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset, supporting the theory that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.
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27
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Liao W, Wang Z, Zhang X, Shu H, Wang Z, Liu D, Zhang Z. Cerebral blood flow changes in remitted early- and late-onset depression patients. Oncotarget 2017; 8:76214-76222. [PMID: 29100305 PMCID: PMC5652699 DOI: 10.18632/oncotarget.19185] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 06/17/2017] [Indexed: 01/08/2023] Open
Abstract
Abnormal cerebral blood flow (CBF) is reportedly associated with major depressive disorder (MDD). We have investigated CBF changes in early-onset depression (EOD) and late-onset depression (LOD), and their impact on cognitive function. Thirty-two remitted EOD patients, 32 remitted LOD patients, and 43 age-matched healthy controls were recruited, and the pulsed arterial spin labeling data were scanned under 3.0T MRI and processed through voxel-by-voxel statistical analysis. Compared to healthy controls, LOD patients had decreased normalized CBF in the bilateral precuneus, cuneus, right fronto-cingulate-striatal areas, and right temporal, occipital and parietal lobes, but increased normalized CBF in the left frontal and temporal cortices and the cingulate gyrus. EOD patients had decreased normalized CBF in the left cerebellum and right calcarine/lingual/fusiform gyrus, and increased normalized CBF in right angular gyrus. LOD patients displayed hemispheric asymmetry in CBF, and had more regions with abnormal CBF than EOD patients. A significant correlation between abnormal CBF and impaired cognitive function was detected in LOD patients, but not EOD patients. These results demonstrate greater CBF abnormalities in LOD patients than EOD patients, and suggest these CBF changes may be associated with progressive degradation of cognitive function in LOD patients.
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Affiliation(s)
- Wenxiang Liao
- Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu 210009, China
| | - Ze Wang
- Center for Cognition and Brain Disorders, Hangzhou Normal University, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Xiangrong Zhang
- Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu 210009, China.,Department of Geriatric Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Hao Shu
- Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu 210009, China
| | - Zan Wang
- Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu 210009, China
| | - Duan Liu
- Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu 210009, China
| | - Zhijun Zhang
- Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu 210009, China
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28
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Byun MS, Choe YM, Sohn BK, Yi D, Han JY, Park J, Choi HJ, Baek H, Lee JH, Kim HJ, Kim YK, Yoon EJ, Sohn CH, Woo JI, Lee DY. Association of Cerebral Amyloidosis, Blood Pressure, and Neuronal Injury with Late-Life Onset Depression. Front Aging Neurosci 2016; 8:236. [PMID: 27790137 PMCID: PMC5061734 DOI: 10.3389/fnagi.2016.00236] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 09/23/2016] [Indexed: 01/14/2023] Open
Abstract
Previous literature suggests that Alzheimer's disease (AD) process may contribute to late-life onset depression (LLOD). Therefore, we investigated the association of LLOD with cerebral amyloidosis and neuronal injury, the two key brain changes in AD, along with vascular risks. Twenty nine non-demented individuals who first experienced major depressive disorder (MDD) after age of 60 years were included as LLOD subjects, and 27 non-demented elderly individuals without lifetime experience of MDD were included as normal controls (NC). Comorbid mild cognitive impairment (MCI) was diagnosed in 48% of LLOD subjects and in 0% of NC. LLOD, irrespective of comorbid MCI diagnosis, was associated with prominent prefrontal cortical atrophy. Compared to NC, LLOD subjects with comorbid MCI (LLODMCI) showed increased cerebral 11C-Pittsburg compound B (PiB) retention and plasma beta-amyloid 1–40 and 1–42 peptides, as measures of cerebral amyloidosis; and, such relationship was not observed in overall LLOD or LLOD without MCI (LLODwoMCI). LLOD subjects, particularly the LLODwoMCI, had higher systolic blood pressure (SBP) than NC. When analyzed in the same multiple logistic regression model that included prefrontal gray matter (GM) density, cerebral amyloidosis, and SBP as independent variables, only prefrontal GM density showed a significant independent association with LLOD regardless of MCI comorbidity status. Our findings suggest AD process might be related to LLOD via prefrontal neuronal injury in the MCI stage, whereas vascular processes—SBP elevation, in particular—are associated with LLOD via prefrontal neuronal injury even in cognitively intact or less impaired individuals.
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Affiliation(s)
- Min Soo Byun
- Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University Seoul, South Korea
| | - Young Min Choe
- Department of Neuropsychiatry, Ulsan University Hospital Ulsan, South Korea
| | - Bo Kyung Sohn
- Department of Neuropsychiatry, Seoul Metropolitan Government-Seoul National University Boramae Medical Center Seoul, South Korea
| | - Dahyun Yi
- Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University Seoul, South Korea
| | - Ji Young Han
- Department of Neuropsychiatry, Seoul National University Hospital Seoul, South Korea
| | - Jinsick Park
- Department of Biomedical Engineering, Hanyang University Seoul, South Korea
| | - Hyo Jung Choi
- Department of Neuropsychiatry, Seoul National University Hospital Seoul, South Korea
| | - Hyewon Baek
- Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly Yongin, South Korea
| | - Jun Ho Lee
- Department of Neuropsychiatry, Seoul National University Hospital Seoul, South Korea
| | - Hyun Jung Kim
- Department of Neuropsychiatry, Changsan Convalescent Hospital Changwon, South Korea
| | - Yu Kyeong Kim
- Department of Nuclear Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center Seoul, South Korea
| | - Eun Jin Yoon
- Department of Nuclear Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center Seoul, South Korea
| | - Chul-Ho Sohn
- Department of Radiology, Seoul National University Hospital Seoul, South Korea
| | - Jong Inn Woo
- Department of Psychiatry, Seoul National University College of Medicine Seoul, South Korea
| | - Dong Young Lee
- Institute of Human Behavioral Medicine, Medical Research Center, Seoul National UniversitySeoul, South Korea; Department of Neuropsychiatry, Seoul National University HospitalSeoul, South Korea; Department of Psychiatry, Seoul National University College of MedicineSeoul, South Korea
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Chakrabarty T, Hadjipavlou G, Lam RW. Cognitive Dysfunction in Major Depressive Disorder: Assessment, Impact, and Management. FOCUS (AMERICAN PSYCHIATRIC PUBLISHING) 2016; 14:194-206. [PMID: 31975803 PMCID: PMC6519654 DOI: 10.1176/appi.focus.20150043] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Cognitive dysfunction is increasingly being recognized as an important clinical dimension in major depressive disorder. This review summarizes the existing data on the epidemiology, assessment, and treatment of cognitive dysfunction among nonelderly adults with the disorder. Overall, cognitive dysfunction is prevalent, persists through periods of symptom remission, and may be independently associated with functional outcomes. However, although the evidence increasingly suggests that clinicians should be heedful of their patients' cognitive functioning, there is as yet no consensus on how best to monitor cognition clinically. In addition, although most studies have reported improved cognition with antidepressant medications, psychotherapy, and neuromodulation, the clinical significance of these improvements is unclear, and high-level evidence to guide decision making is limited. Nonetheless, given the important functional implications, clinicians should assess and monitor cognition and optimize both medication and psychological treatments to mitigate cognitive dysfunction among patients with major depressive disorder.
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Affiliation(s)
- Trisha Chakrabarty
- The authors are with the Department of Psychiatry, University of British Columbia, and the Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Columbia, Canada. Send correspondence to Dr. Lam (e-mail: )
| | - George Hadjipavlou
- The authors are with the Department of Psychiatry, University of British Columbia, and the Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Columbia, Canada. Send correspondence to Dr. Lam (e-mail: )
| | - Raymond W Lam
- The authors are with the Department of Psychiatry, University of British Columbia, and the Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Vancouver, British Columbia, Canada. Send correspondence to Dr. Lam (e-mail: )
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30
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Woo YS, Rosenblat JD, Kakar R, Bahk WM, McIntyre RS. Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE 2016; 14:1-16. [PMID: 26792035 PMCID: PMC4730927 DOI: 10.9758/cpn.2016.14.1.1] [Citation(s) in RCA: 109] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 07/21/2015] [Accepted: 08/26/2015] [Indexed: 01/19/2023]
Abstract
Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit.
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Affiliation(s)
- Young Sup Woo
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.,Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Joshua D Rosenblat
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.,Department of Psychiatry, University of Toronto, Toronto
| | - Ron Kakar
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.,Department of Psychiatry, Western University, London, Ontario, Canada
| | - Won-Myong Bahk
- Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Roger S McIntyre
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.,Department of Psychiatry, University of Toronto, Toronto
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31
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Malhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, Hopwood M, Lyndon B, Mulder R, Murray G, Porter R, Singh AB. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2015; 49:1087-206. [PMID: 26643054 DOI: 10.1177/0004867415617657] [Citation(s) in RCA: 543] [Impact Index Per Article: 54.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To provide guidance for the management of mood disorders, based on scientific evidence supplemented by expert clinical consensus and formulate recommendations to maximise clinical salience and utility. METHODS Articles and information sourced from search engines including PubMed and EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (MDC) (e.g., books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Information was reviewed and discussed by members of the MDC and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous successive consultation and external review involving: expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest in mood disorders. RESULTS The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (Mood Disorders CPG) provide up-to-date guidance and advice regarding the management of mood disorders that is informed by evidence and clinical experience. The Mood Disorders CPG is intended for clinical use by psychiatrists, psychologists, physicians and others with an interest in mental health care. CONCLUSIONS The Mood Disorder CPG is the first Clinical Practice Guideline to address both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus. MOOD DISORDERS COMMITTEE Professor Gin Malhi (Chair), Professor Darryl Bassett, Professor Philip Boyce, Professor Richard Bryant, Professor Paul Fitzgerald, Dr Kristina Fritz, Professor Malcolm Hopwood, Dr Bill Lyndon, Professor Roger Mulder, Professor Greg Murray, Professor Richard Porter and Associate Professor Ajeet Singh. INTERNATIONAL EXPERT ADVISORS Professor Carlo Altamura, Dr Francesco Colom, Professor Mark George, Professor Guy Goodwin, Professor Roger McIntyre, Dr Roger Ng, Professor John O'Brien, Professor Harold Sackeim, Professor Jan Scott, Dr Nobuhiro Sugiyama, Professor Eduard Vieta, Professor Lakshmi Yatham. AUSTRALIAN AND NEW ZEALAND EXPERT ADVISORS Professor Marie-Paule Austin, Professor Michael Berk, Dr Yulisha Byrow, Professor Helen Christensen, Dr Nick De Felice, A/Professor Seetal Dodd, A/Professor Megan Galbally, Dr Josh Geffen, Professor Philip Hazell, A/Professor David Horgan, A/Professor Felice Jacka, Professor Gordon Johnson, Professor Anthony Jorm, Dr Jon-Paul Khoo, Professor Jayashri Kulkarni, Dr Cameron Lacey, Dr Noeline Latt, Professor Florence Levy, A/Professor Andrew Lewis, Professor Colleen Loo, Dr Thomas Mayze, Dr Linton Meagher, Professor Philip Mitchell, Professor Daniel O'Connor, Dr Nick O'Connor, Dr Tim Outhred, Dr Mark Rowe, Dr Narelle Shadbolt, Dr Martien Snellen, Professor John Tiller, Dr Bill Watkins, Dr Raymond Wu.
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Affiliation(s)
- Gin S Malhi
- Discipline of Psychiatry, Kolling Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, St Leonards, NSW, Australia
| | - Darryl Bassett
- School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia School of Medicine, University of Notre Dame, Perth, WA, Australia
| | - Philip Boyce
- Discipline of Psychiatry, Sydney Medical School, Westmead Clinical School, University of Sydney, Sydney, NSW, Australia
| | - Richard Bryant
- School of Psychology, University of New South Wales, Sydney, NSW, Australia
| | - Paul B Fitzgerald
- Monash Alfred Psychiatry Research Centre (MAPrc), Monash University Central Clinical School and The Alfred, Melbourne, VIC, Australia
| | - Kristina Fritz
- CADE Clinic, Discipline of Psychiatry, Sydney Medical School - Northern, University of Sydney, Sydney, NSW, Australia
| | - Malcolm Hopwood
- Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia
| | - Bill Lyndon
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia Mood Disorders Unit, Northside Clinic, Greenwich, NSW, Australia ECT Services Northside Group Hospitals, Greenwich, NSW, Australia
| | - Roger Mulder
- Department of Psychological Medicine, University of Otago-Christchurch, Christchurch, New Zealand
| | - Greg Murray
- Department of Psychological Sciences, School of Health Sciences, Swinburne University of Technology, Melbourne, VIC, Australia
| | - Richard Porter
- Department of Psychological Medicine, University of Otago-Christchurch, Christchurch, New Zealand
| | - Ajeet B Singh
- School of Medicine, Deakin University, Geelong, VIC, Australia
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Lebedeva A, Borza T, Håberg AK, Idland AV, Dalaker TO, Aarsland D, Selbaek G, Beyer MK. Neuroanatomical correlates of late-life depression and associated cognitive changes. Neurobiol Aging 2015; 36:3090-3099. [PMID: 26277679 DOI: 10.1016/j.neurobiolaging.2015.04.020] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 04/25/2015] [Accepted: 04/27/2015] [Indexed: 01/08/2023]
Abstract
We compared cortical thickness between patients with late-life depression (LLD) and healthy controls and between patients with early-onset (EOD) and late-onset (LOD) depression. We also tested age effects on cortical thickness in LLD and controls and if cortical thickness and hippocampal volumes were associated with cognitive performance in LLD. Three-dimensional T1-weighted magnetic resonance images were obtained in 49 LLD and 49 matched hospital controls and processed using FreeSurfer. General linear model analysis was used as a statistical approach. LLD group had thinning in the left parahippocampal, fusiform, and inferior-parietal cortex compared with controls. Age correlated with cortical thinning in controls but not in LLD. Women in the LOD groups had extensive cortical thinning in the lateral prefrontal cortex bilaterally compared with EOD women. Absence of statistically significant changes observed in men should however be treated with caution because of the low number of men in the study. Mini-Mental Status Examination score correlated with lateral prefrontal cortical thickness bilaterally and hippocampal volume in the total group of LLD and in LOD but not EOD. LLD is associated with cortical thinning, which is associated with age at depression onset, gender, and level of cognitive functioning.
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Affiliation(s)
- Aleksandra Lebedeva
- Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
| | - Tom Borza
- Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway
| | - Asta Kristine Håberg
- Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; Department of Medical Imaging, St Olav University Hospital, Trondheim, Norway
| | - Ane-Victoria Idland
- Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Campus AHUS, University of Oslo, Oslo, Norway
| | - Turi Olene Dalaker
- Department of Radiology, Stavanger University Hospital, Stavanger, Norway
| | - Dag Aarsland
- Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden; Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Geir Selbaek
- Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway; Norwegian National Advisory Unit for Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway; Akershus University Hospital, Lørenskog, Norway
| | - Mona K Beyer
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Inamura K, Shinagawa S, Nagata T, Tagai K, Nukariya K, Nakayama K. White matter hyperintensities are associated with the severity of late-life somatoform disorders and executive functions. Nord J Psychiatry 2015:1-8. [PMID: 26107407 DOI: 10.3109/08039488.2015.1053096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND Medically unexplained symptoms are often seen in the elderly. Recently, correlations between medically unexplained symptoms and somatoform disorders (SDs) have been reported. The existence of many interactive psychiatric aetiologies is known among SDs. Late-life SDs might be influenced by some aetiological factors caused by ageing processes, such as structural changes in the brain and cognitive dysfunctions. AIMS Under such circumstances, we investigated the presence of subcortical white matter hyperintensities (WMHs), which increase with ageing, and hypothesized that subcortical WMHs are related to the disease severity of late-life SDs. Furthermore, we confirmed whether cognitive dysfunction influences this process. METHODS To evaluate these hypotheses, we examined patients with medically unexplained symptoms who met the criteria for undifferentiated somatoform disorder and divided the patients into three groups according to the degree of subcortical WMHs: grade 0, grade 1, and grade 2. The subcortical WMHs were rated using Fazekas grading. Differences in symptom severity and cognitive functions were compared among the three groups. RESULTS The grade 2 group had the severest symptoms. Furthermore, the grade 2 group had lower cognitive function scores than the other groups. CONCLUSIONS The present study showed that the presence of subcortical WMHs in patients with late-life SDs was a predictor of disease severity. Moreover, cognitive dysfunction appeared to play a role in the advancement of disease severity.
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Affiliation(s)
- Keisuke Inamura
- Keisuke Inamura, Department of Psychiatry, Jikei University School of Medicine, Kashiwa Hospital , Chiba , Japan
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Sabesan P, Lankappa S, Khalifa N, Krishnan V, Gandhi R, Palaniyappan L. Transcranial magnetic stimulation for geriatric depression: Promises and pitfalls. World J Psychiatry 2015; 5:170-181. [PMID: 26110119 PMCID: PMC4473489 DOI: 10.5498/wjp.v5.i2.170] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 03/04/2015] [Accepted: 04/14/2015] [Indexed: 02/05/2023] Open
Abstract
As the global population gets older, depression in the elderly is emerging as an important health issue. A major challenge in treating geriatric depression is the lack of robust efficacy for many treatments that are of significant benefit to depressed working age adults. Repetitive transcranial magnetic stimulation (rTMS) is a novel physical treatment approach used mostly in working age adults with depression. Many TMS trials and clinics continue to exclude the elderly from treatment citing lack of evidence in this age group. In this review, we appraise the evidence regarding the safety and efficacy of rTMS in the elderly. A consistent observation supporting a high degree of tolerability and safety among the elderly patients emerged across the Randomised Controlled Trials and the uncontrolled trials. Further, there is no reliable evidence negating the utility of rTMS in the elderly with depression. We also identified several factors other than age that moderate the observed variations in the efficacy of rTMS in the elderly. These factors include but not limited to: (1) brain atrophy; (2) intensity and number of pulses (dose-response relationship); and (3) clinical profile of patients. On the basis of the current evidence, the practice of excluding elderly patients from TMS clinics and trials cannot be supported.
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Affiliation(s)
- Sophia Wang
- Department of Psychiatry and Behavior Sciences, Duke University Medical Center, Durham, North Carolina 27710; ,
- Durham Veterans Affairs Medical Center, Durham, North Carolina 27705
| | - Dan G. Blazer
- Department of Psychiatry and Behavior Sciences, Duke University Medical Center, Durham, North Carolina 27710; ,
- Center for the Study of Aging, Duke University Medical Center, Durham, North Carolina 27710
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Reinlieb M, Ercoli L, Siddarth P, St. Cyr N, Lavretsky H. The patterns of cognitive and functional impairment in amnestic and non-amnestic mild cognitive impairment in geriatric depression. Am J Geriatr Psychiatry 2014; 22:1487-95. [PMID: 24315561 PMCID: PMC4751142 DOI: 10.1016/j.jagp.2013.10.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2013] [Revised: 08/28/2013] [Accepted: 10/31/2013] [Indexed: 10/26/2022]
Abstract
OBJECTIVES Depressed older adults are at risk for the development of mild cognitive impairment (MCI), but few studies have characterized MCI subtypes in geriatric depression. The objective of this study was to identify the clinical patterns of MCI in late-life depression. DESIGN Baseline demographic, clinical, and neuropsychological test data collected as part of a randomized antidepressant trial for geriatric depression. SETTING UCLA-based outpatient clinic. PARTICIPANTS One hundred thirty-eight older adults with major depression. MEASUREMENTS A neuropsychological test battery and comprehensive evaluations of depression, apathy, quality of life, medical burden, and vascular risk factors. RESULTS Seventy-one participants (51%) had MCI and 67 (49%) were cognitively normal. Of subjects with MCI, 14 (20%) had amnestic MCI and 57 (80%) had non-amnestic MCI. Overall, patients with MCI had greater depression severity, poorer quality of life, and worse performance on the Mini-Mental State Exam than patients without MCI. Patients with non-amnestic MCI had significantly greater depression severity than patients without MCI. Across all subjects, depression severity correlated with impaired performance in language and visuospatial functioning. CONCLUSION Our findings suggest that MCI is associated with greater severity of depression, poorer quality of life, and worse global cognitive function. Overall, subtypes of MCI in geriatric depression differ in the patterns of functional impairment, which may require different therapeutic approaches.
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Affiliation(s)
| | | | | | | | - Helen Lavretsky
- UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA.
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Mackin RS, Nelson JC, Delucchi KL, Raue PJ, Satre DD, Kiosses DN, Alexopoulos GS, Arean PA. Association of age at depression onset with cognitive functioning in individuals with late-life depression and executive dysfunction. Am J Geriatr Psychiatry 2014; 22:1633-41. [PMID: 24680502 PMCID: PMC4145037 DOI: 10.1016/j.jagp.2014.02.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2013] [Revised: 02/21/2014] [Accepted: 02/24/2014] [Indexed: 01/18/2023]
Abstract
OBJECTIVE To compare patterns of cognitive performance in older adults with late-onset depression (LOD; ≥65 years of age) with that of older adults with early-onset depression (EOD; <65 years). METHODS Participants were 171 adults aged 60 years or older with major depression and executive dysfunction who were participating in a randomized psychotherapy trial. Participants included 72 LOD and 99 EOD individuals. Cognitive performance on measures of verbal learning, memory, and executive functioning were evaluated. Demographic and clinical characteristics, severity of cerebrovascular risk factors, and disability ratings were also compared between groups. RESULTS The LOD group was older and had fewer previous episodes of depression and lower severity of depression compared with EOD participants. The LOD group demonstrated poorer performance on measures of verbal learning (F(1,161) = 4.28, p = 0.04) and memory (F(1,160) = 4.65, p = 0.03) than the EOD group. Linear regression analysis demonstrated that LOD and fewer years of education were significant predictors of poorer verbal learning (F(7,114) = 6.25, p <0.001) and memory (F(7,113)=7.24, p <0.001). Performance on measures of executive functioning, severity of vascular risk factors, and disability ratings did not differ between the two groups. CONCLUSION In older adults with depression and executive dysfunction, LOD was associated with poorer performance on measures of verbal learning and memory. Aging-related brain changes associated with LOD may play a more important role, leading to dysfunction in these cognitive domains than a history of recurrent depressive episodes in older adults with a dysexecutive syndrome.
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Affiliation(s)
- R. Scott Mackin
- University of California, San Francisco, Department of Psychiatry,Center for Imaging of Neurodegenerative Disease, Veterans Administration Medical Center, San Francisco, CA, USA
| | - J. Craig Nelson
- University of California, San Francisco, Department of Psychiatry
| | - Kevin L Delucchi
- University of California, San Francisco, Department of Psychiatry
| | | | - Derek D Satre
- University of California, San Francisco, Department of Psychiatry,Weill Cornell Medical College, Department of Psychiatry
| | | | | | - Patricia A Arean
- University of California, San Francisco, Department of Psychiatry
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Disabato BM, Morris C, Hranilovich J, D’Angelo G, Zhou G, Wu N, Doraiswamy PM, Sheline YI. Comparison of brain structural variables, neuropsychological factors, and treatment outcome in early-onset versus late-onset late-life depression. Am J Geriatr Psychiatry 2014; 22:1039-46. [PMID: 23768683 PMCID: PMC3815480 DOI: 10.1016/j.jagp.2013.02.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Revised: 01/31/2013] [Accepted: 02/04/2013] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To compare differences in gray matter volumes, white matter and subcortical gray matter hyperintensities, neuropsychological factors, and treatment outcome between early- and late-onset late-life depressed (LLD) subjects. METHODS We conducted a prospective, nonrandomized, controlled trial at the outpatient clinics at Washington University and Duke University on 126 subjects, aged 60 years or older, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression, scored 20 or more on the Montgomery-Asberg Depression Rating Scale (MADRS), and received neuropsychological testing and magnetic resonance imaging. Subjects were excluded for cognitive impairment or severe medical disorders. After 12 weeks of sertraline treatment, subjects' MADRS scores over time and neuropsychological factors were studied. RESULTS Left anterior cingulate thickness was significantly smaller in the late-onset depressed group than in the early-onset LLD subjects. The late-onset group also had more hyperintensities than the early-onset LLD subjects. No differences were found in neuropsychological factor scores or treatment outcome between early-onset and late-onset LLD subjects. CONCLUSION Age at onset of depressive symptoms in LLD subjects are associated with differences in cortical thickness and white matter and subcortical gray matter hyperintensities, but age at onset did not affect neuropsychological factors or treatment outcome.
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Affiliation(s)
- Brianne M. Disabato
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO USA
| | - Carrie Morris
- Department of Medicine, Washington University School of Medicine, St. Louis, MO USA
| | - Jennifer Hranilovich
- Department of Medicine, Washington University School of Medicine, St. Louis, MO USA
| | - Gina D’Angelo
- Division of Biostatistics, Washington University School of Medicine, St. Louis, MO USA
| | - Gongfu Zhou
- Division of Biostatistics, Washington University School of Medicine, St. Louis, MO USA
| | - Ningying Wu
- Division of Biostatistics, Washington University School of Medicine, St. Louis, MO USA
| | - P. Murali Doraiswamy
- Division of Biological Psychiatry, Duke University School of Medicine, Durham, NC USA
| | - Yvette I. Sheline
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO USA,Department of Radiology, Washington University School of Medicine, St. Louis, MO USA,Department of Neurology, Washington University School of Medicine, St. Louis, MO USA
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Abstract
This brief report provides an introduction to the topic of cognitive functioning in late-life depression (LLD). In addition to providing a review of the literature, we present a framework for understanding the heterogeneity of cognitive outcomes in this highly prevalent disorder. In addition, we discuss the relationship between LLD and dementia, and highlight the importance of regularly assessing cognitive functioning in older adults who present with depressive symptoms. If cognitive deficits are discovered during a neuropsychological assessment, we recommend referral to a geriatric psychiatrist or cognitive neurologist, for evaluation and treatment of the patient's symptoms.
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40
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Wu RH, Feng C, Xu Y, Hua T, Liu XY, Fang M. Late-onset depression in the absence of stroke: associated with silent brain infarctions, microbleeds and lesion locations. Int J Med Sci 2014; 11:587-92. [PMID: 24782647 PMCID: PMC4003543 DOI: 10.7150/ijms.8025] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Accepted: 03/25/2014] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Late-onset depression (LOD) is a frequent mood disorder among elderly. Previous studies have proved that LOD is associated with cerebral silent lesions especially white matter lesions (WML) and yielded the "vascular depression" hypothesis to explain the pathogenesis of LOD. However, there were relatively few studies about the association between silent brain infarctions (SBIs), microbleeds (MBs) and the prevalence of LOD. In this study we sought to evaluate the presence, accumulation and locations of SBIs and MBs, and explore the possible association between them and LOD. METHODS 65 patients of LOD diagnosed according to DSM-IV and 270 subjects of control group were enrolled and scanned by MRI to analyze the presence, numbers and locations of SBIs and MBs. Clinical and radiological characteristics were compared between LOD patients and control group. Logistic regression models were constructed to identify the independent risk factors for LOD. RESULTS LOD patients had higher prevalence and numbers of both SBIs and MBs. SBIs and MBs in the left hemisphere, SBIs in basal ganglia and lobar MBs were all independent risk factors for LOD. CONCLUSION The presence of both SBIs and MBs were associated with a higher rate LOD. Lesions in some specific locations might be critical for the presence of LOD.
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Affiliation(s)
- Ri-Han Wu
- 1. Department of Neurology, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Shanghai, China
| | - Chao Feng
- 1. Department of Neurology, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Shanghai, China
- 2. Yiwu Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang, China
| | - Yu Xu
- 3. Department of Radiology, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Shanghai, China
| | - Ting Hua
- 3. Department of Radiology, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Shanghai, China
| | - Xue-Yuan Liu
- 1. Department of Neurology, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Shanghai, China
| | - Min Fang
- 1. Department of Neurology, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Shanghai, China
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The neurobiological pathogenesis of poststroke depression. ScientificWorldJournal 2014; 2014:521349. [PMID: 24744682 PMCID: PMC3973123 DOI: 10.1155/2014/521349] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2013] [Accepted: 01/28/2014] [Indexed: 12/14/2022] Open
Abstract
Poststroke depression (PSD) is an important consequence after stroke, with negative impact on stroke outcome. The pathogenesis of PSD is complicated, with some special neurobiological mechanism, which mainly involves neuroanatomical, neuron, and biochemical factors and neurogenesis which interact in complex ways. Abundant studies suggested that large lesions in critical areas such as left frontal lobe and basal ganglia or accumulation of silent cerebral lesions might interrupt the pathways of monoamines or relevant pathways of mood control, thus leading to depression. Activation of immune system after stroke produces more cytokines which increase glutamate excitotoxicity, results in more cell deaths of critical areas and enlargement of infarctions, and, together with hypercortisolism induced by stress or inflammation after stroke which could decrease intracellular serotonin transporters, might be the key biochemical change of PSD. The interaction among cytokines, glucocorticoid, and neurotrophin results in the decrease of hippocampal neurogenesis which has been proved to be important for mood control and pharmaceutical effect of selective serotonin reuptake inhibitors and might be another promising pathway to understand the pathogenesis of PSD. In order to reduce the prevalence of PSD and improve the outcome of stroke, more relevant studies are still required to clarify the pathogenesis of PSD.
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Pompili M, Innamorati M, Di Vittorio C, Sher L, Girardi P, Amore M. Sociodemographic and clinical differences between suicide ideators and attempters: a study of mood disordered patients 50 years and older. Suicide Life Threat Behav 2014; 44:34-45. [PMID: 23937195 DOI: 10.1111/sltb.12051] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Accepted: 05/19/2013] [Indexed: 11/27/2022]
Abstract
Our study sought to characterize mood disordered suicide ideators and attempters 50 years and older admitted to a psychiatric ward either for a recent suicide attempt or for ongoing suicidal ideation. We enrolled 50 patients with suicide ideation consecutively admitted to an inpatient department and 50 patients admitted for a suicide attempt made in the last 48 hours. Suicide attempters more frequently had low social support and an age of onset of mood disorder of 46 years and older, and less frequently had a history of suicidal behaviors in the family members and pharmacological treatment, despite the fact that the groups did not differ with regard to antidepressants prescribed. The groups were not distinguishable based on several variables assumed to be risk factors for suicide behavior, such as proximal life events and stressors or alcohol use disorders. In both samples, comorbidity with organic diseases, the presence of stressful life events in the past 12 months, and a diagnosis of major depression were frequently reported. In conclusion, the presence of low social support and the absence of a pharmacotherapy may increase suicidal behaviors in patients at risk.
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Affiliation(s)
- Maurizio Pompili
- Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
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Verdelho A, Madureira S, Moleiro C, Ferro JM, O'Brien JT, Poggesi A, Pantoni L, Fazekas F, Scheltens P, Waldemar G, Wallin A, Erkinjuntti T, Inzitari D. Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: the LADIS study. J Neurol Neurosurg Psychiatry 2013; 84:1250-4. [PMID: 23715914 DOI: 10.1136/jnnp-2012-304191] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC). METHODS The LADIS (Leukoaraiosis And DISability in the elderly) prospective study evaluated the impact of WMC on the transition of independent older subjects into disability. Subjects were evaluated annually over a 3 year period with a comprehensive clinical and neuropsychological evaluation. Previous episodes of depression and current DS were assessed during each interview. Severity of DS was assessed using the self-rated 15 item Geriatric Depression Scale. A neuropsychological battery and clinical criteria for cognitive impairments were applied in all clinical visits, and cognitive compound measures were made based on neuropsychological results. MRI was performed at baseline and at year 3. RESULTS 639 subjects were included (74.1 ± 5 years old, 55% women, 9.6 ± 3.8 years of schooling). Dementia was diagnosed in 90 patients and cognitive impairment not dementia in 147 patients at the last clinical evaluation. DS were an independent predictor of cognitive impairment (dementia and not dementia) during follow-up, independent of the effect of the severity of WMC, medial temporal lobe atrophy, age, education or global cognitive function at baseline. CONCLUSIONS DS are associated with an increase risk of cognitive decline, independent of the effect of WMC, probably due to an additive or synergistic effect. In this context, DS probably represent a subtle ongoing organic dysfunction.
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Affiliation(s)
- Ana Verdelho
- Department of Neurociences, University of Lisbon, Santa Maria Hospital, , Lisbon, Portugal
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Pimontel MA, Reinlieb ME, Johnert LC, Garcon E, Sneed JR, Roose SP. The external validity of MRI-defined vascular depression. Int J Geriatr Psychiatry 2013; 28:1189-96. [PMID: 23447432 DOI: 10.1002/gps.3943] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2012] [Accepted: 01/11/2013] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Multiple diagnostic criteria have been used to define vascular depression (VD). As a result, there are discrepancies in the clinical characteristics that have been established for the illness. The aim of this study was twofold. First, we used empirically established diagnostic criteria to determine the clinical characteristics of magnetic resonance imaging (MRI)-defined VD. Second, we assessed the agreement between a quantitative and qualitative method for identifying the illness. METHOD We examined the baseline clinical and neuropsychological profile of 38 patients from a larger, double-blind, randomized, 12-week clinical trial comparing nortriptyline with sertraline in depressed older adults. Ten patients met quantitative criteria for MRI-defined VD based on the highest quartile of deep white matter hyperintensity (DWMH) volume. Fourteen patients met qualitative criteria for MRI-defined VD based on a DWMH score of 2 or higher on the Fazekas' modified Coffey rating scale. RESULTS Age, gender, cumulative illness rating scale-geriatric (CIRS-G) score, two measures of psychomotor retardation [the psychomotor retardation item of the Hamilton Rating Scale for Depression (HRSD) as well as performance on the Purdue Pegboard], and performance on the Stroop Color/Word test (a measure of the response inhibition component of executive functioning) were significantly different between those with VD and non-VD. CONCLUSIONS Patients with VD have a distinct clinical and neuropsychological profile that is mostly consistent across different methods for identifying the illness. These findings support the notion that MRI-defined VD represents a unique and valid subtype of late-life depression.
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Affiliation(s)
- Monique A Pimontel
- Department of Psychology, The Graduate Center, City University of New York, New York, NY, USA
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Taylor WD, Aizenstein HJ, Alexopoulos GS. The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry 2013; 18:963-74. [PMID: 23439482 PMCID: PMC3674224 DOI: 10.1038/mp.2013.20] [Citation(s) in RCA: 591] [Impact Index Per Article: 49.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Revised: 01/09/2013] [Accepted: 01/18/2013] [Indexed: 02/07/2023]
Abstract
The 'Vascular Depression' hypothesis posits that cerebrovascular disease may predispose, precipitate or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between LLD, vascular risk factors and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in LLD, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor, influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression, but also provide guidance on the potential repurposing of pharmacological agents that may improve LLD outcomes.
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Affiliation(s)
- W D Taylor
- Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University, Nashville, TN 37212, USA.
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Namekawa Y, Baba H, Maeshima H, Nakano Y, Satomura E, Takebayashi N, Nomoto H, Suzuki T, Arai H. Heterogeneity of elderly depression: increased risk of Alzheimer's disease and Aβ protein metabolism. Prog Neuropsychopharmacol Biol Psychiatry 2013; 43:203-8. [PMID: 23276885 DOI: 10.1016/j.pnpbp.2012.12.016] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 12/07/2012] [Accepted: 12/19/2012] [Indexed: 12/17/2022]
Abstract
Epidemiological studies have proposed that depression may increase the risk for Alzheimer's disease (AD), even in patients with early-onset depression. Although metabolism of amyloid β protein (Aβ) in elderly depression received attention in terms of their correlation, there is a serious heterogeneity in elderly depression in terms of age at onset of depression. Moreover, it is unknown whether early-onset major depressive disorder (MDD) has a long-term effect on the involvement of Aβ metabolism and later development of AD. Thus, we evaluated serum Aβ40 and Aβ42 levels, the Aβ40/Aβ42 ratio in 89 elderly (≥60 years of age) inpatients with MDD and 81 age-matched healthy controls, and compared them among patients with early-onset (<60 years) and late-onset (≥60years) MDD and controls. The results showed that the serum Aβ40/Aβ42 ratio was significantly higher in patients with both early- and late-onset MDD than in controls (early-onset, p=0.010; late-onset, p=0.043), and it is of great interest that the serum Aβ40/Aβ42 ratio was negatively correlated with the age at MDD onset (R=-0.201, p=0.032). These results suggest that an earlier onset of MDD may have a more serious abnormality in Aβ metabolism, possibly explaining a biological mechanism underlying the link between depression and AD.
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Affiliation(s)
- Yuki Namekawa
- Juntendo University Mood Disorder Project (JUMP), Department of Psychiatry, Juntendo Koshigaya Hospital, Saitama, Japan
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Paulson D, Bowen ME, Lichtenberg PA. Does brain reserve protect older women from vascular depression? J Gerontol B Psychol Sci Soc Sci 2013; 69:157-67. [PMID: 23448867 DOI: 10.1093/geronb/gbt007] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVES Brain reserve theory, typically discussed in relation to dementia, was examined with regard to late-life depression symptomatology and cerebrovascular burden (CVB) in older-old women. METHOD It was predicted that in a 6-year longitudinal sample (Health and Retirement Study) of 1,355 stroke-free women aged 80 years and older, higher levels of depressive symptomatology (8-item Center for Epidemiologic Studies-Depression score) would be predicted by high CVB, less educational attainment, and the education × CVB interaction after controlling for age and cognitive functioning (Telephone Interview for Cognitive Status). A latent growth curve model was used to identify differences in depression symptomatology at baseline and over time. Logistic regression analyses were used to predict clinically significant depressive symptomatology at each wave based on CVB, education, and the education × CVB interaction. RESULTS Results indicate that among older women, greater educational attainment predicted fewer depression symptoms at baseline, but this advantage was partially eroded over time. The education × CVB interaction predicted clinically significant depressive symptoms at baseline when the benefits of education were most robust. DISCUSSION Brain reserve, characterized by educational attainment, may counterbalance the effect of high CVB with respect to depressive symptoms, thereby preserving mood in late life. These findings support the application of brain reserve theory to late-life depression.
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Affiliation(s)
- Daniel Paulson
- Correspondence should be addressed to Daniel Paulson, Institute of Gerontology and Department of Psychology, Wayne State University, 87 East Ferry Street, 226 Knapp Building, Detroit, MI 48202. E-mail:
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Sachs-Ericsson N, Corsentino E, Moxley J, Hames JL, Collins N, Sawyer K, Selby EA, Joiner T, Zarit S, Gotlib IH, Steffens DC. A longitudinal study of differences in late- and early-onset geriatric depression: depressive symptoms and psychosocial, cognitive, and neurological functioning. Aging Ment Health 2013; 17:1-11. [PMID: 22934752 PMCID: PMC3535510 DOI: 10.1080/13607863.2012.717253] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Studies suggest early-onset depression (EOD) is associated with a more severe course of the depressive disorder, while late-onset depression (LOD) is associated with more cognitive and neuroimaging changes. This study examined if older adults with EOD, compared with those with LOD, would exhibit more severe symptoms of depression and, consistent with the glucocorticoid cascade hypothesis, have more hippocampal volume loss. A second goal was to determine if LOD, compared with EOD, would demonstrate more cognitive and neuroimaging changes. METHOD At regular intervals over a four-year period non-demented, older, depressed adults were assessed on the Mini-Mental Status Examination and the Montgomery-Asberg Depression Rating Scale. They were also assessed on magnetic resonance imaging. RESULTS Compared with LOD, EOD had more depressive symptoms, more suicidal thoughts, and less social support. Growth curve analyses indicated that EOD demonstrated higher levels of residual depressive symptoms over time. The LOD group exhibited a greater decrement in cognitive scores. Contrary to the glucocorticoid cascade hypothesis, participants with EOD lost right hippocampal volume at a slower rate than did participants with LOD. Right cerebrum gray matter was initially smaller among participants with LOD. CONCLUSIONS EOD is associated with greater severity of depressive illness. LOD is associated with more severe cognitive and neurological changes. These differences are relevant to understanding cognitive impairment in geriatric depression.
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Snyder HR. Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychol Bull 2013; 139:81-132. [PMID: 22642228 PMCID: PMC3436964 DOI: 10.1037/a0028727] [Citation(s) in RCA: 1080] [Impact Index Per Article: 90.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cognitive impairments are now widely acknowledged as an important aspect of major depressive disorder (MDD), and it has been proposed that executive function (EF) may be particularly impaired in patients with MDD. However, the existence and nature of EF impairments associated with depression remain strongly debated. Although many studies have found significant deficits associated with MDD on neuropsychological measures of EF, others have not, potentially due to low statistical power, task impurity, and diverse patient samples, and there have been no recent, comprehensive, meta-analyses investigating EF in patients with MDD. The current meta-analysis uses random-effects models to synthesize 113 previous research studies that compared participants with MDD to healthy control participants on at least one neuropsychological measure of EF. Results of the meta-analysis demonstrate that MDD is reliably associated with impaired performance on neuropsychological measures of EF, with effect sizes ranging from 0.32 to 0.97. Although patients with MDD also have slower processing speed, motor slowing alone cannot account for these results. In addition, some evidence suggests that deficits on neuropsychological measures of EF are greater in patients with more severe current depression symptoms, and those taking psychotropic medications, whereas evidence for effects of age was weaker. The results are consistent with the theory that MDD is associated with broad impairment in multiple aspects of EF. Implications for treatment of MDD and theories of EF are discussed. Future research is needed to establish the specificity and causal link between MDD and EF impairments.
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Affiliation(s)
- Hannah R Snyder
- Department of Psychology and Neuroscience, University of Colorado, Boulder, CO 80309, USA.
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