Vascular dementia (VaD) includes a group of brain disorders that are characterized by cerebrovascular pathology.Neuroinflammation, disruption of the blood-brain barrier (BBB) permeability, white matter lesions, and neuronal loss are all significant pathological manifestations of VaD and play a key role in disease progression. Necroptosis, also known asprogrammed necrosis, is a mode of programmed cell death distinct from apoptosis and is closely associated with ischemic injury and neurodegenerative diseases. Recent studies have shown that necroptosis in VaD exacerbates BBB destruction, activates neuroinflammation, promotes neuronal loss, and severely affects VaD prognosis.

In this review, we outline the significant roles of necroptosis and its molecular mechanisms in the pathological process of VaD, with a particular focus on the role of necroptosis in modulating neuroinflammation and exacerbating the disruption of BBB permeability in VaD, and elaborate on the molecular regulatory mechanisms and the centrally involved cells of necroptosis mediated by tumor necrosis factor-α in neuroinflammation in VaD. We also analyze the possibility and specific strategy that targeting necroptosis would help inhibit neuroinflammation and BBB destruction in VaD. With a focus on necroptosis, this study delved into its impact on the pathological changes and prognosis of VaD to provide new treatment ideas.

Evidence in the literature suggests an association between Type 2 Diabetes Mellitus (T2DM) and dementia, but this relationship has not been studied in the most recently available nationally representative datasets. This retrospective, observational, cross-sectional study of adults (60+ years of age) seeks to investigate this association across racial and ethnic groups in the most recently available National Ambulatory Medical Care Survey (NAMCS) datasets. A multivariable logistic regression model is employed to investigate the association between T2DM and the diagnosis of dementia and assess disparities in racial and ethnic groups, while controlling for available covariates of interest. The analysis found no evidence of a relationship between T2DM and dementia even after adjusting for available covariates of interest (OR 1.13, 95% CI = 0.81-1.57). However, evidence of differences in the proportion with dementia was observed between ethnicities and race groups. Hispanic/Latinos were found to have more than double the odds of dementia compared to Non-Hispanic/Latinos (OR 2.08, 95% CI = 1.05-4.14), while the Other race group had 74% lower odds of dementia compared to the White race group (OR 0.26, 95% CI = 0.10-0.64). This study suggests that disparities in the risk of dementia remain for ethnic/racial groups. As minority populations continue to grow, educational and preventative measures for both diabetes and dementia are vital public health priorities. Perceptions of cognitive impairment, its association with T2DM, and the interventions needed to address the deficits may vary by culture and ethnic background; therefore, specific characteristics relevant to these populations should be further evaluated.

Objective: To investigate the risk factors for the development of mild cognitive dysfunction in hypertensive patients in the community and to develop a risk prediction model. Method: The data used in this study were obtained from two sources: the China Health and Retirement Longitudinal Study (CHARLS) and the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 1121 participants from CHARLS were randomly allocated into a training set and a validation set, following a 70:30 ratio. Meanwhile, an additional 4016 participants from CLHLS were employed for external validation of the model. The patients in this study were divided into two groups: those with mild cognitive impairment and those without. General information, employment status, pension, health insurance, and presence of depressive symptoms were compared between the two groups. LASSO regression analysis was employed to identify the most predictive variables for the model, utilizing 14-fold cross-validation. The risk prediction model for cognitive impairment in hypertensive populations was developed using generalized linear models. The model's discriminatory power was evaluated through the area under the receiver operating characteristic (ROC) curve and calibration curves. Results: In the modeling group, eight variables such as gender, age, residence, education, alcohol use, depression, employment status, and health insurance were ultimately selected from an initial pool of 21 potential predictors to construct the risk prediction model. The area under the curve (AUC) values for the training, internal, and external validation sets were 0.777, 0.785, and 0.782, respectively. All exceeded the threshold of 0.7, suggesting that the model effectively predicts the incidence of mild cognitive dysfunction in community-based hypertensive patients. A risk prediction model was developed using a generalized linear model in conjunction with Lasso regression. The model's performance was evaluated using the area under the receiver operating characteristic (ROC) curve. Hosmer-Lemeshow test values yielded p = .346 and p = .626, both of which exceeded the 0.05 threshold. Calibration curves demonstrated a significant agreement between the nomogram model and observed outcomes, serving as an effective tool for evaluating the model's predictive performance. Discussion: The predictive model developed in this study serves as a promising and efficient tool for evaluating cognitive impairment in hypertensive patients, aiding community healthcare workers in identifying at-risk populations.

Recent evidence suggests that diabetes-related lower-extremity complications (DRLECs) may be associated with cognitive changes in people with diabetes. However, existing literature has produced inconsistent findings, and no systematic reviews have been conducted to investigate whether DRLECs impact the cognition of people with diabetes. This systematic review evaluated existing studies that investigated cognition in people with diabetes with DRLECs and without DRLECs.

Seven databases; MEDLINE, PubMed, CINAHL, EMBASE, Cochrane, PsycINFO and Web of Science were searched from inception until 22/8/2022 for studies that compared cognition in people with diabetes with and without DRLECs. Results were independently screened for eligibility and assessed for methodological quality by two authors, with key data extracted. Studies were eligible for meta-analysis if the studies reported similar cases, controls, and outcome measures.

Thirteen studies were included in the review, with eleven of medium methodological quality, one of high quality, and one of low quality. Four studies found significant differences in cognition between those with and without DRLECs, four found significant associations between diabetes-related lower-extremity complications and cognition, and five found no differences or associations. One small meta-analysis of eligible studies found that there was no statistically significant difference in cognition in people without, compared to with, peripheral neuropathy (Mean difference = -0.49; 95%CI: -1.59-0.61; N = 3; n = 215). Leave-one-out sensitivity analyses further confirmed that there was no significant difference in cognition among people with and without peripheral neuropathy (p > 0.05).

DRLECs may be related to cognition in people with diabetes, however, existing evidence is unclear due to variability in used methodologies that may challenge concluding the findings. Future high-quality studies investigating cognition among people with and without DRLECs are needed.

Few studies have examined the relationship between education and cognition among the oldest-old.

Cognitive assessments were conducted biannually for 803 participants (62.6% women) of LifeAfter90, a longitudinal study of individuals ≥ 90 years old. Gender differences in associations between education (< high school, high school, some college, and ≥ college) and cognition (verbal episodic memory, semantic memory, and executive function) were examined at baseline and longitudinally using linear mixed models.

Higher education levels were associated with better cognitive performance at baseline for both men and women. College completion was more strongly associated with better baseline executive function among women. Education-cognition associations for baseline verbal episodic memory and baseline semantic memory did not differ by gender. Education was not associated with a decline in any domain-specific cognitive scores, regardless of gender.

Education is associated with cognitive function among the oldest-old and varies by gender and cognitive domain at baseline but not over time.

In the oldest-old, higher education was associated with better cognitive function. College completion was more strongly associated with executive function in women. Education was not associated with cognitive decline after age 90 regardless of gender. Improving education could decrease gaps in cognitive level among older individuals.

Aging is associated with declines in cognition and brain structural integrity. However, there is equivocality over (1) the specificity of affected domains in different people, (2) the location of associated patterns of brain structural deterioration, and (3) the sociodemographic factors contributing to 'unhealthy' cognition. We aimed to identify cognitive profiles displayed by older adults and determine brain and sociodemographic features potentially shaping these profiles. A sample of Southeast-Asian older adults (N = 386) participated in a multi-session study comprising cognitive testing, neuroimaging, and a structured interview. We used computational models to extract latent mechanisms underlying cognitive flexibility and response inhibition. Data-driven methods were used to construct cognitive profiles based on standard performance measures and model parameters. We also investigated grey matter volume and machine-learning derived 'brain-ages'. A profile associated with poor set-shifting and rigid focusing was associated with widespread grey matter reduction in cognitive control regions. A slow responding profile was associated with advanced brain-age. Both profiles were correlated with poor socioeconomic standing and cognitive reserve. We found that the impact of sociodemographic factors on cognitive profiles was partially mediated by total grey and white matter, and dorsolateral prefrontal and cerebellar volumes. This study furthers understanding of how distinct aging profiles of cognitive impairment uniquely correspond to specific vs. global brain deterioration and the significance of socioeconomic factors in informing cognitive performance in older age.

Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings in additional settings, including clinical.

Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed for generalization. Participants were eligible for inclusion if they had data for CMM and were free of dementia at baseline. Baseline CMM was defined as: 1) CMM 5, ≥2 among hypertension, hyperlipidemia, diabetes, stroke, and heart disease and 2) CMM 3 (aligned with previous studies), ≥2 among diabetes, stroke, and heart disease. Baseline depression was primarily characterized by binary classification of depressive symptom measurements, employing the Geriatric Depression Scale and the Center for Epidemiological Studies-Depression scale. Global cognition was standardized as z-scores through harmonizing multiple cognitive measures. Longitudinal cognition was calculated as changes in global cognitive z-scores. A pooled individual participant data (IPD) analysis was utilized to estimate the independent and joint associations of CMM and depression on cognitive outcomes in COSMIC studies, both cross-sectionally and longitudinally. Repeated analyses were performed in three external validation studies.

Of the 32,931 older adults in the 14 COSMIC cohorts, we included 30,382 participants with complete data on baseline CMM, depression, and cognitive assessments for cross-sectional analyses. Among them, 22,599 who had at least 1 follow-up cognitive assessment were included in the longitudinal analyses. The three external studies for validation had 1964 participants from 3 multi-ethnic Asian older adult cohorts in different settings (community-based, memory clinic, and post-stroke study). In COSMIC studies, each of CMM and depression was independently associated with cross-sectional and longitudinal cognitive function, without significant interactions between them (Ps > 0.05). Participants with both CMM and depression had lower cross-sectional cognitive performance (e.g. β = -0.207, 95% CI = (-0.255, -0.159) for CMM5 (+)/depression (+)) and a faster rate of cognitive decline (e.g. β = -0.040, 95% CI = (-0.047, -0.034) for CMM5 (+)/depression (+)), compared with those without either condition. These associations remained consistent after additional adjustment for APOE genotype and were robust in two-step random-effects IPD analyses. The findings regarding the joint association of CMM and depression on cognitive function were reproduced in the three external validation studies.

Our findings highlighted the importance of investigating age-related co-morbidities in a multi-dimensional perspective. Targeting both cardiometabolic and psychological conditions to prevent cognitive decline could enhance effectiveness.

Natural Science Foundation of China and National Institute on Aging/National Institutes of Health.

This study examined educational and occupational inequality as two aspects of social determinants of health that might mediate the longitudinal relationship between racialization and late life cognitive level and change. Participants were 2371 individuals racialized as Black and White from the ACTIVE study who provided occupational data. Data were analyzed from baseline and five assessments over 10-years using structural equation modeling. Black/White race served as the predictor, occupational complexity (OC) and years of education as mediators, and cognitive (memory, reasoning, and speed of processing) intercept, linear slope, and quadratic slope as the dependent variables. Black/White race showed significant indirect associations through education and OC on level of performance in cognition, linear change in reasoning and memory, and quadratic change in reasoning. Education and OC accounted for 11-16% of the association between race and cognitive level and represent modifiable social determinants of health that are associated with disparities in cognitive aging.

Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear.

To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajectory prestroke in stroke survivors with the trajectory of individuals without incident stroke over follow-up.

The study used harmonized and pooled data from 14 population-based cohort studies included in the Cohort Studies of Memory in an International Consortium collaboration. These studies were conducted from 1993 to 2019 across 11 countries among community-dwelling older adults without a history of stroke or dementia. For this study, linear mixed-effects models were used to estimate trajectories of cognitive function poststroke relative to a stroke-free cognitive trajectory. The full model adjusted for demographic and vascular risk factors. Data were analyzed from July 2022 to March 2024.

Incident stroke.

The primary outcome was global cognition, defined as the standardized average of 4 cognitive domains (language, memory, processing speed, and executive function). Cognitive domain scores were formed by selecting the most commonly administered test within each domain and standardizing the scores.

The study included 20 860 participants (12 261 [58.8%] female) with a mean (SD) age of 72.9 (8.0) years and follow-up of 7.51 (4.2) years. Incident stroke was associated with a substantial acute decline in global cognition (-0.25 SD; 95% CI, -0.33 to -0.17 SD), the Mini-Mental State Examination, and all cognitive domains (ranging from -0.17 SD to -0.22 SD), as well as accelerated decline in global cognition (-0.038 SD per year; 95% CI, -0.057 to -0.019 SD per year) and all domains except memory (ranging from -0.020 to -0.055 SD per year), relative to a stroke-free cognitive trajectory. There was no significant difference in prestroke slope in stroke survivors compared with the rate of decline in individuals without stroke in all cognitive measures. The mean rate of decline without a previous stroke was -0.049 SD per year (95% CI, -0.051 to -0.047 SD) in global cognition.

In this cohort study using pooled data from 14 cohorts, incident stroke was associated with acute and accelerated long-term cognitive decline in older stroke survivors.

This study aimed to investigate the cognitive profile and prospective cognitive changes in non-demented adults with elevated Modified Dementia Risk Scores (MDRS), while also exploring the potential relationship between these associations and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology and neuroinflammation.

Within the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database, 994 participants without dementia were assessed on MDRS, CSF biomarkers and cognition. We examined the associations of the MDRS with CSF biomarkers and cognitive scores using linear regressions. Causal mediation analyses were conducted to analyze the associations among MDRS, brain pathologies, and cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study was used to validate the mediation effects and to investigate the longitudinal association between MDRS and cognitive decline.

The results revealed that higher MDRS were linked to poorer cognitive performance (Model 1: PFDR  < 0.001; Model 2: PFDR  < 0.001) and increases in CSF levels of phosphorylated tau (P-tau, Model 1: PFDR  < 0.001; Model 2: PFDR  < 0.001), total tau (T-tau, Model 1: PFDR  < 0.001; Model 2: PFDR  < 0.001), P-tau/Aβ42 ratio (Model 1: PFDR  = 0.023; Model 2: PFDR  = 0.028), T-tau/Aβ42 ratio (Model 1: PFDR  < 0.001; Model 2: PFDR  < 0.001) and soluble triggering receptor expressed on myeloid cells 2 (sTrem2, Model 1: PFDR  < 0.001; Model 2: PFDR  < 0.001) in the CABLE study. The impact of MDRS on cognition was partially mediated by neuroinflammation and tau pathology. These mediation effects were replicated in the ADNI study. Baseline MDRS were significantly associated with future cognitive decline, as indicated by lower scores on the Mini-Mental State Examination (MMSE, Model 1: PFDR  = 0.045; Model 2: PFDR  < 0.001), ADNI composite memory score (ADNI-MEM, Model 1: PFDR  = 0.005; Model 2: PFDR  < 0.001), ADNI composite executive function score (ADNI-EF, Model 1: PFDR  = 0.045; Model 2: PFDR  < 0.001), and higher score on the Alzheimer's Disease Assessment Scale (ADAS13, Model 1: PFDR  = 0.045; Model 2: PFDR  < 0.001).

The findings of this study revealed significant associations between MDRS and cognitive decline, suggesting a potential role of tau pathology and neuroinflammation in the link between MDRS and poorer cognitive performance in individuals without dementia. Consequently, the MDRS holds promise as a tool for targeted preventive interventions in individuals at high risk of cognitive impairment.

Subjective health ratings are associated with dementia risk such that those who rate their health more poorly have increased risk for dementia. The genetic and environmental mechanisms underlying this association are unclear, as prior research cannot rule out whether the association is due to genetic confounds. The current study addresses this gap in two samples of twins, one from Sweden (N = 548) and one from Denmark (N = 4,373). Using genetically-informed, bivariate regression models, we assessed whether additive genetic effects explained the association between subjective health and dementia risk as indexed by a latent variable proxy measure. Age at intake, sex, education, depressive symptomatology, and follow-up time between subjective health and dementia risk assessments were included as covariates. Results indicate that genetic variance and other sources of confounding accounted for the majority of the effect of subjective health ratings on dementia risk. After adjusting for genetic confounding and other covariates, a small correlation was observed between subjective health and latent dementia risk in the Danish sample (rE = - .09, p < .05). The results provide further support for the genetic association between subjective health and dementia risk, and also suggest that subjective ratings of health measures may be useful for predicting dementia risk.

The association of cognitive function, its changes, and all-cause mortality has not reached a consensus, and the independence of the association between changes in cognitive function and mortality remains unclear. The purpose of this study was to evaluate the longitudinal association between baseline cognitive function and cognitive changes over 1 year with subsequent all-cause mortality among the older adults aged 60 and above.

A prospective cohort study utilizing the Community Older Adults Health Survey data. Initiated in 2018, the study annually assessed all individuals aged 60+ in Dalang Town, Dongguan City. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). A total of 6,042 older adults individuals were included, and multivariate Cox proportional hazard models were used to examine cognitive function's impact on mortality.

Participants' median age was 70 years, with 39% men. Over a median 3.08-year follow-up, 525 died. Mortality risk increased by 6% per MMSE score decrease (adjusted HR = 1.06, 95%CI: 1.05-1.08). Compared to those with normal cognitive function at baseline, participants with mild cognitive impairment and moderate to severe cognitive impairment had significantly higher mortality risks (adjusted HR = 1.40, 95%CI: 1.07-1.82; HR = 2.49, 95%CI: 1.91-3.24, respectively). The risk of death was 5% higher for each one-point per year decrease in cognitive function change rate (HR = 1.05, 95%CI: 1.02-1.08). Compared with participants with stable cognitive function, those with rapid cognitive decline had a 79% increased risk of death (adjusted HR = 1.79, 95% CI: 1.11-2.87), with baseline cognitive function influencing this relationship significantly (P for interaction = 0.002).

Baseline cognitive impairment and rapid cognitive decline are associated with higher all-cause mortality risks in Chinese older adults. Baseline function influences the mortality impact of cognitive changes.

The observational studies investigated the impact of migraine on Alzheimer's Disease (AD). However, these findings were limited by confounding factors and reverse causation, leading to contradictory results.

We utilized Univariable Mendelian Randomization (UVMR) to explore the link between migraine (13,971 cases/470,627 controls) and AD risk (Bellenguez et al., 39,106 cases/46,828 controls; FinnGen, 111,471 cases/111,471 controls). Meta-analysis was performed for comprehensive synthesis. Employing Multivariable Mendelian Randomization (MVMR), we created models incorporating migraine and 35 potential AD risk factors, examining migraine's independent impact on AD onset risk under considering these factors.

The meta-analysis of inverse variance weighted MR results, combining data from Bellenguez et al. (odds ratio (OR) [95% confidence interval (CI)]: 1.5717 [1.1868-2.0814], p = 0.0016) and FinnGen (OR [95% CI]: 1.2904 [0.5419-3.0730], p = 0.5646), provided evidence for a causal relationship between genetically predicted migraine and the heightened risk of AD occurrence (OR [95% CI]: 1.54 [1.18, 2.00], p < 0.01). After adjusting for Diastolic blood pressure (OR [95% CI]: 1.4120 [0.8487-2.3493], p = 0.1840) and Tumor necrosis factor alpha (OR [95% CI]: 1.2411 [0.8352-1.8443], p = 0.2852), no discernible association was detected between migraine and the risk of AD.

This study offers compelling evidence indicating a significant correlation between genetically predicted migraine and an elevated risk of AD.

The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics.

We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis.

A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed.

Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups.

A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Memory deficits are observed across psychiatric disorders ranging from the prodrome of psychosis to common mental disorders such as anxiety, depression, and dissociative disorders. Memory deficits among patients recovering from psychiatric disorders could be directly related to the primary illness or secondary to the adverse effect of a treatment such as Electroconvulsive Therapy (ECT). The trouble in the meaningful integration of working-memory and episodic memory is the most commonly affected domain that requires routine assessments. An update on the recent trends of methods of assessment of memory deficits is the first step towards understanding and correcting these deficits to target optimum recovery. A systematic literature search was conducted from October 2018 to October 2022 to review the recent methods of assessment of memory deficits in psychiatric disorders. The definition of 'Memory deficit' was operationalized as 'selective processes of memory, commonly required for activities of daily living, and affected among psychiatric disorders resulting in subjective distress and dysfunction'. We included 110 studies, most of them being conducted in western countries on patients with schizophrenia. Other disorders included dementia and mild cognitive impairment. Brief Assessment of Cognition in Schizophrenia, Cambridge Automated Neuropsychological Test Battery, California Verbal Learning Test, Trail Making Test Part A and B, Rey Auditory Verbal Learning Test, Wechsler Memory Scale, Wechsler Adults Intelligence Scale-IV were the most common neuropsychological assessments used. Mini-Mental State Examination and Montreal Cognitive Assessment were the most common bedside assessment tools used while Squire Subjective Memory Questionnaire was commonly used to measure ECT-related memory deficits. The review highlights the recent developments in the field of assessment of memory deficits in psychiatric disorders. Findings recommend and emphasize routine assessment of memory deficits among psychiatric disorders in developing countries especially severe mental illnesses. It remains interesting to see the role of standardized assessments in diagnostic systems given more than a decade of research on memory deficits in psychiatric disorders.

Frailty is associated with a poor prognosis in older patients with heart failure (HF). However, multidomain frailty assessment tools have not been established in patients with HF, and the association between the frailty phenotype and the deficit-accumulation frailty index in these patients is unclear. We aimed to understand this relationship and evaluate the prognostic value of the deficit-accumulation frailty index in older patients with HF.

We retrospectively analyzed FRAGILE-HF cohort, which consisted of prospectively registered hospitalized patients with HF aged ≥ 65 years. The frailty index was calculated using 34 health-related items. The physical, social, and cognitive domains of frailty were evaluated using a phenotypic approach. The primary endpoint was all-cause mortality.

Among 1027 patients with HF (median age, 81 years; male, 58.1%; median frailty index, 0.44), a higher frailty index was associated with a higher prevalence in all domains of cognitive, physical, and social frailty defined by the phenotype model. During the 2-year follow-up period, a higher frailty index was independently associated with all-cause death even after adjustment for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score plus log B-type natriuretic peptide (per 0.1 increase: hazard ratio, 1.21; 95% confidence interval, 1.07-1.37; P = 0.002). The addition of the frailty index to the baseline model yielded statistically significant incremental prognostic value (net reclassification improvement, 0.165; 95% confidence interval, 0.012-0.318; P = 0.034).

A higher frailty index was associated with a higher prevalence of all domains of frailty defined by the phenotype model and provided incremental prognostic information with pre-existing risk factors in older patients with HF.

The impact of dietary intake on cognitive outcomes and dementia prevention is a topic of increasing interest. Meta-analyses of observational studies, mostly conducted within US and European populations, have reported benefits of healthy diet patterns on cognitive performance, but results from individual studies have been inconsistent. These inconsistencies are likely due to the diverse methodology used in studies, including different diet and cognitive function assessment instruments, follow-up periods, and analytical methods, which make drawing conclusions relevant to dietary guidance challenging. The objective of this project is to describe a protocol to conduct a retrospective harmonization study on dietary intake and cognitive health using data from European and US studies. The recommendations resulting from the project can be used to support evidence-based synthesis for future iterations of the Dietary Guidelines for Americans or other population-based dietary guidance. Additionally, this study will serve as a harmonization guide for future research on the relationship between diet patterns and cognition. The approach outlined ultimately aims to optimize resources and expedite research efforts for dementia prevention.

To examine sex differences in the cognitive trajectories of a nationally representative sample of older people living in China and to explore potential determinants of these trajectories.

The study included 2230 women and 2171 men who were cognitively healthy and aged over 60 at the first observation from the Chinese Longitudinal Healthy Longevity Survey based on the 2008-2018 cohort. Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (MMSE). Group-based trajectory modeling was used to identify potential heterogeneity of longitudinal changes over the 10 years in each gender. Logistic regression was used to investigate associations between baseline characteristics (age, education, fertility history, sleep length, physical activity, and health status and behaviors) and trajectory classes.

Three trajectories (labeled stable, slow decline, and rapid decline) were identified according to the changes in MMSE scores for both women and men. For the women, both the slow and rapid decline groups accounted for a larger proportion (14.7% and 11.0%, respectively) than the male decline groups (8.1% and 6.6%, respectively), and the women had a lower baseline MMSE score with a faster decline. In the multivariable logistic regression analyses, older age, less education, older age at first birth, poorer functional abilities, hearing impairment, and lower baseline MMSE scores were significantly associated with cognitive decline in both the female and male groups compared to the stable group. For the women, sleeping over 9 h was also associated with a rapid cognitive decline trajectory, while current exercise and being overweight/obese were protective factors against cognitive decline.

The women had an overall more serious cognitive decline than men. The potential determinants of cognitive decline identified in this study could be considered for developing specific intervention strategies aimed at promoting a healthy brain and preventing cognitive decline in different sexes, especially in low-income and developing countries.

 With aging, some cognitive abilities change because of neurobiological processes. Cognition may also be influenced by psychosocial aspects.

 To describe the relationship between a measure of neuroticism, depression symptoms, purpose in life, and cognitive performance in community-dwelling older adults.

 This was a cross-sectional analysis based on the data from the second wave of the Frailty in Brazilian Older Adults (FIBRA) study, carried out between 2016 and 2017. The sample consisted of 419 older people (≥ 72 years old) cognitively unimpaired and mostly with low education. The variables of interest were sociodemographic, Neuroticism domain from the NEO-PI-R, Geriatric Depression Scale (GDS), Purpose in Life (PiL) scale, and a cognitive composite score which included the Mini-Mental State Examination (MMSE), and the scores for the sub-items of the Mini-Addenbrooke's Cognitive Examination (M-ACE), namely, Verbal Fluency (VF) - Animal, Clock Drawing Test (CDT), Episodic Memory (name and address).

 There was a greater number of women (70%), with older age (median = 80 years, IQR = 77-82), and low education (median = 4 years, IQR = 2-5). In the bivariate correlations, years of education (ρ = 0.415; p < 0.001) and PiL (ρ = 0.220; p < 0.001) were positively associated with cognition. Neuroticism (ρ = -0.175; p < 0.001) and depression symptoms (ρ = -0.185; p < 0.001) were negatively associated with cognition. In the logistic regression, after including confounding variables, the associations between cognition and PiL (OR = 2.04; p = 0.007) and education (OR = 1.32; p < 0.001) remained significant.

 Low PiL and low education levels were associated with worse cognition among older adults. Such results may be of relevance in programs that aim to improve cognition among older adults.

In this systematic review and meta-analysis, we critically evaluate available evidence regarding the association between primary headaches and subsequent decline of cognitive function and dementia.

Recent studies suggested that headache disorders may increase the risk for dementia. However, available studies are conflicting.

To identify qualifying studies, we searched scientific databases, including Pubmed, Scopus, Web of Science, Science Direct and BMC, screening for relevant papers. In order to reduce the heterogeneity between different studies, the analyses were further subdivided according to the clinical diagnoses and the study methodologies.

We identified 23 studies investigating the association between primary headaches and the risk of dementia. Of these, 18 met our inclusion criteria for meta-analysis (covering 924.140 individuals). Overall effect-size shows that primary headaches were associated with a small increase in dementia risk (OR = 1,15; CI 95%: 1,03-1,28; p = 0,02). Analyzing subgroups, we found that migraine was associated with both a moderate increased risk of all-cause dementia (OR = 1,26; p = 0,00; 95% CI: 1,13-1,40) as well as a moderate increased risk of Alzheimer's disease (OR = 2,00; p = 0,00; 95% CI: 1,46-2,75). This association was significant in both case-control and retrospective cohort studies but not in prospective studies.

Our study supports the presence of a link between primary headaches and dementia. However, in the subgroup analysis, only patients with migraine showed a moderate increase risk for all-cause dementia and for Alzheimer's disease. Additional rigorous studies are needed to elucidate the possible role of primary headaches on the risk of developing cognitive impairment and dementia.

A comprehensive view of factors associated with AD/ADRD will significantly aid in studies to develop new treatments for AD/ADRD and identify high-risk populations and patients for prevention efforts. In our study, we summarized the risk factors for AD/ADRD by reviewing existing meta-analyses and review articles on risk and preventive factors for AD/ADRD. In total, we extracted 477 risk factors in 10 categories from 537 studies. We constructed an interactive knowledge map to disseminate our study results. Most of the risk factors are accessible from structured Electronic Health Records (EHRs), and clinical narratives show promise as information sources. However, evaluating genomic risk factors using RWD remains a challenge, as genetic testing for AD/ADRD is still not a common practice and is poorly documented in both structured and unstructured EHRs. Considering the constantly evolving research on AD/ADRD risk factors, literature mining via NLP methods offers a solution to automatically update our knowledge map.

Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of cardiovascular disorders, with recent evidence linking pre-eclampsia with vascular dementia. We examined associations of HDP with cognitive performance measured in midlife, in a prospective cohort study, the Avon Longitudinal Study of Parents and Children. Six cognitive function domains were measured 20 years after pregnancy at a mean age of 51 years. The cognition tests were repeated at clinics in the following two years. Cognitive function domains measured were immediate and delayed verbal episodic memory, working memory, processing speed, verbal intelligence, and verbal fluency. Exposures were pre-eclampsia, gestational hypertension (GH), and a combined category of any HDP, all compared to normotensive pregnancy. Of 3393 pregnancies included in the analysis, GH was experienced by 417 (12.3%) and pre-eclampsia by 57 (1.7%). GH was associated with lower verbal episodic memory, in the delayed logic memory test (-0.16 SDs; 95% CI -0.30, -0.03; p = .015) and there was weak evidence of an association with the immediate logic memory test (-0.13 SDs; -0.27, 0.001; p = .058). However, we did not see steeper declines by age for women with GH and there was no evidence of associations with other cognitive domains or for pre-eclampsia with any domains. Results were not substantially changed after controlling for midlife blood pressure. Our findings suggest that a history of GH is associated with slightly reduced episodic memory 20 years after pregnancy, but we found no evidence of a quicker age-related decline compared to women with normotensive pregnancies.

Several lifestyle, cardiovascular and psychosocial factors are associated with risk of cognitive decline and dementia. We studied the independent associations of a broad set of modifiable risk factors with decline in processing speed in three large population-based cohorts with up to 23 years of follow-up.

We used data of 9,666 participants from the Doetinchem Cohort Study, the Longitudinal Aging Study Amsterdam, and the Maastricht Aging Study. Decline in processing speed was measured with the letter digit substitution task or the alphabet coding task and modeled using quadratic latent growth curves. Associations of modifiable risk factors with level and rate of decline in processing speed were investigated by estimating associations with level of processing speed at different centering ages.

Latent growth curves showed that decline in processing speed accelerated with age. Smoking, not drinking alcohol and depressive symptoms were associated with a lower level of processing speed in all cohorts. In two of the cohorts, more physical activity, drinking more than two glasses of alcohol per day, higher BMI and diabetes were associated with a lower level of processing speed. Depressive symptoms and diabetes were also associated with faster decline in processing speed.

Several modifiable risk factors are associated with the level of processing speed in older age, while few are also related to the rate of decline.

Abnormal cognitive aging is closely related to dementia.

This study aimed to estimate the effect of cardiovascular health (CVH) metrics on abnormal cognitive aging.

A longitudinal cohort study.

Participants were recruited from the Chinese Longitudinal Health Longevity Survey.

A total of 3298 participants aged ≥65 years with normal cognitive performance at baseline were included.

Cognitive performance was measured by the Chinese version of the Mini-Mental State Examination (MMSE). CVH was assessed with six metrics, including hypertension, diabetes, exercise, body mass index (BMI), diet, and smoking. Group-based trajectory model was used to identify the trajectory groups of cognitive aging over 12 years (2002-2014 and 2005-2018). The parametric g-formula was applied to estimate the effect of each single six CVH metrics and their combinations on the 12-year cognitive aging trajectory.

Four trajectory groups of cognitive aging were identified: Stable-high (77.4%), Unstable (4.9%), Slow decline (11.1%), and Rapid decline (6.6%). Unstable, Slow decline, and Rapid decline trajectory groups were considered as abnormal cognitive aging (22.6%). Single interventions on hypertension, exercise, BMI, and diet could reduce the risk of abnormal cognitive aging. Moreover, the risk ratios of joint intervention on exercise, BMI, and diet for Unstable, Slow decline, and Rapid decline trajectory groups were 0.38 (95% CI: 0.30-0.48), 0.45 (95% CI: 0.37-0.54), and 0.3 (95% CI: 0.23-0.41), respectively.

A considerable proportion of the participants experienced abnormal cognitive aging during their aging process. Interventions on these CVH metrics (i.e., exercise, BMI, and diet), which are fairly practical and feasible for older adults, may be effective strategies for preventing abnormal cognitive aging.

White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions.

We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains.

Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing.

The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.