Search

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

Background and Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles ( P P =0.015). Lower performance was attributed largely to Word List Recall ( P P ≤0.01). The scores for left versus right carotid disease were similar. Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02089217.

Introduction Early detection of cognitive decline in older adults is a public health priority. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA), a multisite study, is validating cognition, emotion, motor, and sensory modules of the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in the aging spectrum from cognitively normal to dementia of the Alzheimer's type (DAT). Methods Participants 65 to 85 years old, in demographic groups racially proportional to the general US population, are recruited in one of three groups to validate the NIHTB: cognitively normal, amnestic mild cognitive impairment (aMCI), or mild DAT. Additional special emphasis cohorts include (1) Blacks in the three clinical groups; (2) Spanish-speakers in the three clinical groups; (3) cognitively normal, population-proportional, over age 85. Discussion Longitudinal study will determine whether NIHTB can predict cognitive decline and is associated with Alzheimer's disease biomarkers. Here, we detail the methods for the ARMADA study.

Background: Meta-analyses of individuals’ cognitive data are increasing to investigate the biomedical, lifestyle, and sociocultural factors that influence cognitive decline and dementia risk. Pre-statistical harmonization of cognitive instruments is a critical methodological step for accurate cognitive data harmonization, yet specific approaches for this process are unclear. Objective: To describe pre-statistical harmonization of cognitive instruments for an individual-level meta-analysis in the blood pressure and cognition (BP COG) study. Methods: We identified cognitive instruments from six cohorts (the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Coronary Artery Risk Development in Young Adults study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study) and conducted an extensive review of each item’s administration and scoring procedures, and score distributions. Results: We included 153 cognitive instrument items from 34 instruments across the six cohorts. Of these items, 42%were common across ≥2 cohorts. 86%of common items showed differences across cohorts. We found administration, scoring, and coding differences for seemingly equivalent items. These differences corresponded to variability across cohorts in score distributions and ranges. We performed data augmentation to adjust for differences. Conclusion: Cross-cohort administration, scoring, and procedural differences for cognitive instruments are frequent and need to be assessed to address potential impact on meta-analyses and cognitive data interpretation. Detecting and accounting for these differences is critical for accurate attributions of cognitive health across cohort studies.

OBJECTIVE Type 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS Cross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic BP (SBP) and diastolic BP (DBP), hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test, letter and animal fluency tests, and Digit Symbol Substitution Test (DSST). RESULTS Among 5,047 GRADE participants, 5,018 (99.4%) completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, and 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores, whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modestly better DSST scores. Hypertension history was not related to cognition. CONCLUSIONS In people with type 2 diabetes of a mean duration of

Background Accelerated epigenetic aging using DNA methylation (DNAm)-based biomarkers has been reported in people with human immunodeficiency virus (HIV, PWH), but limited data are available among African Americans (AA), women, and older PWH. Methods DNAm was measured using Illumina EPIC Arrays for 107 (69 PWH and 38 HIV-seronegative controls) AA adults ≥60 years in New York City. Six DNAm-based biomarkers of aging were estimated: (1) epigenetic age acceleration (EAA), (2) extrinsic epigenetic age acceleration (EEAA), (3) intrinsic epigenetic age acceleration (IEAA), (4) GrimAge, (5) PhenoAge, and (6) DNAm-estimated telomere length (DNAm-TL). The National Institutes of Health (NIH) Toolbox Cognition Battery (domains: executive function, attention, working memory, processing speed, and language) and Montreal Cognitive Assessment (MoCA) were administered. Participants were assessed for frailty by the Fried criteria. Results The PWH and control groups did not differ by sex, chronological age, or ethnicity. In total, 83% of PWH had a viral load Conclusions Evidence of epigenetic age acceleration was observed in AA older PWH using DNAm-based biomarkers of aging. There was no evidence of age acceleration independent of cell type National Institutes of Health composition (IEAA) associated with HIV, but this measure was associated with decreased cognitive function among PWH.

INTRODUCTION: There is limited and inconsistent reporting on the association between Life’s Simple 7 (LS7) and dementia in the elderly population. METHODS: Based on Washington Heights-Inwood Columbia Aging Project (WHICAP) study, LS7 scores were estimated to assess cardiovascular health status. Associations between LS7 scores and incident dementia were investigated by Cox proportional hazards models. RESULTS: Among 1987 subjects, 291 incident cases of dementia were identified over a median follow-up of 5.84 years. Compared with subjects in the poor cardiovascular health group (scores 0 to 5), those in intermediate (6 to 9) and optimal (10 to 14) groups had lower dementia risk, with the hazard ratio (HR; 95% confidence interval [CI]) being 0.74 (0.54 to 1.00) and 0.59 (0.38 to 0.91), respectively. These results were significant in Apolipoprotein E genotype ε4 (APOE-ε4) allele noncarriers but not in carriers. DISCUSSION: Higher LS7 scores are protective for dementia, especially among the APOE-ε4 noncarriers.

Background and Objectives Leisure activity engagement (LAE) may reduce the risk of incident dementia. However, cognitive performance may predict LAE change. We evaluated the temporal ordering of overall and subtypes of LAE (intellectual, physical, and social) and cognitive performance (global, language, memory, and visuospatial function) among non-demented older adults. Research Design and Methods The Washington Heights–Inwood Columbia Aging Project concurrently administered a survey measure of 13 leisure activities and a neuropsychological battery every 18–24 months for up to 14 years to 5,384 racially and ethnically diverse participants. We used parallel process conditional latent growth curve models to examine temporal ordering in the overall sample and within baseline diagnostic groups (mild cognitive impairment [MCI] vs. cognitively normal). Results Levels and changes of overall and subtypes of LAE were positively correlated with cognitive performance in the overall sample and within each diagnostic group. In the overall sample, higher initial memory was associated with slower declines in social LAE (estimate = 0.019, 95% confidence interval [95% CI]: 0.001–0.037). Among MCI, higher initial physical LAE was associated with slower declines in memory (estimate = 0.034, 95% CI: 0.001–0.067), but higher initial intellectual LAE was related to steeper declines in visuospatial function (estimate = −0.028, 95% CI: −0.052 to −0.004). Among cognitively normal, higher initial memory was associated with slower declines in intellectual LAE (estimate = 0.012, 95% CI: 0.002−0.022). Discussion and Implications Dynamic interplay of LAE with cognitive performance was observed across diagnostic groups. Levels of LAE subtypes could be more predictive of change in certain cognitive domains within older adults with MCI.

Introduction Blood‐based Alzheimer's disease (AD) biomarkers provide opportunities for community studies and across ethnic groups. We investigated blood biomarker concentrations in the Washington Heights‐Inwood Columbia Aging Project (WHICAP), a multi‐ethnic community study of aging and dementia. Methods We measured plasma amyloid beta (Aβ)40, Aβ42, total tau (t‐tau), phosphorylated tau (p‐tau)181, and p‐tau217, and neurofilament light chain (NfL) in 113 autopsied participants (29% with high AD neuropathological changes) and in 300 clinically evaluated individuals (42% with clinical AD). Receiver operating characteristics were used to evaluate each biomarker. We also investigated biomarkers as predictors of incident clinical AD. Results P‐tau181, p‐tau217, and NfL concentrations were elevated in pathologically and clinically diagnosed AD. Decreased Aβ42/Aβ40 ratio and increased p‐tau217 and p‐tau181 were associated with subsequent AD diagnosis. Discussion Blood‐based AD biomarker concentrations are associated with pathological and clinical diagnoses and can predict future development of clinical AD, providing evidence that they can be incorporated into multi‐ethnic, community‐based studies.

Background The neuropeptide neurotensin (NT) has been linked to cardiometabolic disease. Cardiovascular risk factors are being recognized as risk factors for cognitive impairment. Objective To examine the association of the stable precursor of NT, pro-neurotensin/neuromedin N (pro-NT/NMN), with incident cognitive impairment (ICI). Methods We conducted a prospective nested case-control study in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. In 2003-2007, REGARDS enrolled 30,239 Black and White adults aged ≥45 years. ICI was identified using a 3-test cognitive battery administered biannually. Baseline pro-NT/NMN was measured by immunoassay in 393 cases of ICI and 490 controls after 3.4 years follow up. Multivariable logistic regression was used to calculate odds ratios (OR) of ICI by pro-NT/NMN quartiles. Race, age, and sex differences were studied with stratified models and interaction testing. Results Pro-NT/NMN was higher in Black participants and those with hypertension and diabetes. Women with a 4th versus 1st-quartile pro-NT/NMN had 2.28-fold increased odds of ICI (95% CI 1.08-4.78) after adjusting for risk factors and incident stroke. There was no association of higher pro-NT/NMN quartiles with ICI in the overall group or men. There were no race or age differences in associations. Conclusion In this biracial population-based study, elevated systemic pro-NT/NMN was associated with more than doubled risk of ICI in women but not men. Others reported sex-specific associations in women for cardiovascular mortality and diabetes with higher pro-NT/NMN, supporting a role for future research on sex differences in the neurotensinergic system.

Introduction: High dietary intake of long chain, polyunsaturated fatty acids is associated with lower Alzheimer’s disease (AD) risk. Methods: Washington Heights-Hamilton Heights-Inwood Columbia Aging Project is a multiethnic, prospective observational study of aging and dementia among elderly (≥ 65 years). Dietary intake was measured using a food frequency questionnaire. Dietary short-, medium-, and long-chain fatty acid intakes were categorized by number of carbons and double bonds. Consensus AD diagnoses were made. Associations between AD risk and dietary fatty acid and cholesterol intakes were estimated using multivariable Cox proportional hazards regression models. Results: Of 2612 multiethnic women (67%) and men (baseline age 76.3 [6.4] years), 380 developed AD over an average 4.5 years follow-up. Lower risk of AD was associated with increasing intakes of docosahexaenoic acid (DHA; hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.57 to 0.95, P = 0.018) and eicosapentaenoic acid (EPA; HR = 0.74, 95% CI: 0.57 to 0.95, P = 0.021), and longer AD-free survival (P < 0.05). Discussion: Higher intake of DHA and EPA are protective for AD.

Background and ObjectivesTo investigate sociodemographic and medical predictors of incident mild cognitive impairment (MCI) and subsequent course of MCI at follow-up, including sustained MCI diagnosis, classification as cognitively normal, and progression to dementia.MethodsWithin a community-based cohort, diagnoses of MCI were made with a published algorithm. Diagnosis of dementia was based on clinical consensus. Cox regressions estimated hazard ratios of incident MCI associated with several predictors. Modified Poisson regressions estimated relative risks associated with predictors of diagnostic status at follow-up after incidence.ResultsAmong 2,903 cognitively normal participants at baseline, 752 developed MCI over an average of 6.3 (SD 4.5) years (incidence rate 56 per 1,000 person-years). Presence of APOE ε4 and higher medical burden increased risk of incident MCI, while more years of education, more leisure activities, and higher income decreased this risk. Of the incident MCI cases, after an average of 2.4 years of follow-up, 12.9% progressed to dementia, 9.6% declined in functioning and did not meet the algorithmic criteria for MCI but did not meet the clinical criteria for dementia, 29.6% continued to meet MCI criteria, and 47.9% no longer met MCI criteria. Multidomain MCI, presence of APOE ε4, depressive symptoms, and antidepressant use increased the risk of progression to dementia.DiscussionThis community-based study showed that almost half of the individuals with incident MCI diagnoses were classified as cognitively normal at follow-up. Predictors of incident MCI demonstrably differed from those of subsequent MCI course; these findings can refine expectations for cognitive and functional course of those presenting with MCI.

Social vulnerabilities increase the risk of developing hypertension and lower life expectancy, but the effect of an individual’s overall vulnerability burden is unknown. Our objective was to determine the association of social vulnerability count and the risk of developing hypertension or dying over 10 years and whether these associations vary by race. We used the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) and included participants without baseline hypertension. The primary exposure was the count of social vulnerabilities defined across economic, education, health and health care, neighborhood and built environment, and social and community context domains. Among 5425 participants of mean age 64±10 SD years of which 24% were Black participants, 1468 (31%) had 1 vulnerability and 717 (15%) had ≥2 vulnerabilities. Compared with participants without vulnerabilities, the adjusted relative risk ratio for developing hypertension was 1.16 (95% CI, 0.99–1.36) and 1.49 (95% CI, 1.20–1.85) for individuals with 1 and ≥2 vulnerabilities, respectively. The adjusted relative risk ratio for death was 1.55 (95% CI, 1.24–1.93) and 2.30 (95% CI, 1.75–3.04) for individuals with 1 and ≥2 vulnerabilities, respectively. A greater proportion of Black participants developed hypertension and died than did White participants (hypertension, 38% versus 31%; death, 25% versus 20%). The vulnerability count association was strongest in White participants ( P value for vulnerability count×race interaction: hypertension=0.046, death=0.015). Overall, a greater number of socially determined vulnerabilities was associated with progressively higher risk of developing hypertension, and an even higher risk of dying over 10 years.

https://pubmed.ncbi.nlm.nih.gov/34662699/, White matter hyperintensities (WMH) are areas of increased signal visualized on T2-weighted fluid attenuated inversion recovery (FLAIR) brain magnetic resonance imaging (MRI) sequences. They are typically attributed to small vessel cerebrovascular disease in the context of aging. Among older adults, WMH are associated with risk of cognitive decline and dementia, stroke, and various other health outcomes. There has been increasing interest in incorporating quantitative WMH measurement as outcomes in clinical trials, observational research, and clinical settings. Here, we present a novel, fully automated, unsupervised detection algorithm for WMH segmentation and quantification. The algorithm uses a robust preprocessing pipeline, including brain extraction and a sample-specific mask that incorporates spatial information for automatic false positive reduction, and a half Gaussian mixture model (HGMM). The method was evaluated in 24 participants with varying degrees of WMH (4.9-78.6 cm3) from a community-based study of aging and dementia with dice coefficient, sensitivity, specificity, correlation, and bias relative to the ground truth manual segmentation approach performed by two expert raters. Results were compared with those derived from commonly used available WMH segmentation packages, including SPM lesion probability algorithm (LPA), SPM lesion growing algorithm (LGA), and Brain Intensity AbNormality Classification Algorithm (BIANCA). The HGMM algorithm derived WMH values that had a dice score of 0.87, sensitivity of 0.89, and specificity of 0.99 compared to ground truth. White matter hyperintensity volumes derived with HGMM were strongly correlated with ground truth values (r = 0.97, p = 3.9e-16), with no observable bias (-1.1 [-2.6, 0.44], p-value = 0.16). Our novel algorithm uniquely uses a robust preprocessing pipeline and a half-Gaussian mixture model to segment WMH with high agreement with ground truth for large scale studies of brain aging.

Systemic racism leads to racial/ethnic residential segregation, which can result in health inequities. We examined if the associations between residential segregation and later-life cognition and dementia differed based on segregation measure and by participant race/ethnicity. Tests of memory (n = 4616), language (n = 4333), visuospatial abilities (n = 4557), and incident dementia (n = 4556) were analyzed in older residents of Northern Manhattan, New York (mean age: 75.7 years). Segregation was measured at the block group-level using three indices: dissimilarity, isolation, and interaction. We fit multilevel linear or Cox proportional hazards models and included a race/ethnicity × segregation term to test for differential associations, adjusting for socioeconomic and health factors. Living in block groups with higher proportions of minoritized people was associated with −0.05 SD lower language scores. Living in block groups with higher potential contact between racial/ethnic groups was associated with 0.06–0.1 SD higher language scores. The findings were less pronounced for other cognitive domains and for incident dementia. Non-Hispanic Black adults were most likely to experience negative effects of neighborhood segregation on cognition (language and memory) and dementia. All indices partly capture downstream effects of structural racism (i.e., unequal distributions of wealth/resources) on cognition. Therefore, desegregation and equitable access to resources have the potential to improve later-life cognitive health.

BACKGROUND AND AIM: Age-related cognitive decline is a growing public health issue as increases in life expectancy and the aging of the population are expected to raise the prevalence of cognitive ...

Objective:To estimate the prevalence of mild cognitive impairment (MCI) and its subtypes and investigate the impact of midlife cardiovascular risk factors on late-life MCI among the aging Mexican population.Method:Analyses included a sample of non-demented adults over the age of 55 living in both urban and rural areas of Mexico (N = 1807). MCI diagnosis was assigned based on a comprehensive cognitive assessment assessing the domains of memory, executive functioning, language, and visuospatial ability. The normative sample was selected by means of the robust norms approach. Cognitive impairment was defined by a 1.5-SD cut-off per cognitive domain using normative corrections for age, years of education, and sex. Risk factors included age, education, sex, rurality, depression, insurance status, workforce status, hypertension, diabetes, stroke, and heart disease.Results:The prevalence of amnestic MCI was 5.9%. Other MCI subtypes ranged from 4.2% to 7.7%. MCI with and without memory impairment was associated with older age (OR = 1.01 [1.01, 1.05]; OR = 1.03 [1.01, 1.04], respectively) and residing in rural areas (OR = 1.49 [1.08, 2.06]; OR = 1.35 [1.03, 1.77], respectively). Depression (OR = 1.07 [1.02, 1.12]), diabetes (OR = 1.37 [1.03, 1.82]), and years of education (OR = 0.94 [0.91, 0.97]) were associated with MCI without memory impairment. Midlife CVD increased the odds of MCI in late-life (OR = 1.76 [1.19, 2.59], which was driven by both midlife hypertension and diabetes (OR = 1.70 [1.18, 2.44]; OR = 1.88 [1.19, 2.97], respectively).Conclusions:Older age, depression, low education, rurality, and midlife hypertension and diabetes were associated with higher risk of late-life MCI among older adults in Mexico. Our findings suggest that the causes of cognitive impairment are multifactorial and vary by MCI subtype.

Introduction Odor identification deficits characterize Alzheimer's disease and other dementias. We examined if intact performance on brief cognitive and odor identification tests predicts lack of transition to dementia. Methods In an urban community, 1037 older adults without dementia completed the 40-item University of Pennsylvania Smell Identification Test, which includes the 12-item Brief Smell Identification Test (B-SIT). Data from 749 participants followed up for 4 years were analyzed. Results In covariate-adjusted survival analyses, impairment on the Blessed Orientation Memory Concentration Test and B-SIT each predicted dementia (n = 109), primarily Alzheimer's disease (n = 101). Among participants with intact olfactory (B-SIT ≥ 11/12 correct) and cognitive (Blessed Orientation Memory Concentration Test ≤ 5/28 incorrect) ability, 3.4% (4/117) transitioned to dementia during follow-up with no transitions in the 70–75 and 81–83 years age group quartiles. Discussion Odor identification testing adds value to global cognitive testing, and together can identify individuals who rarely transition to dementia, thereby avoiding unnecessary diagnostic investigation.

Introduction The present study sought to determine whether cognitive trajectories differ between men and women across and within racial/ethnic groups. Methods Participants were 5258 non-Hispanic White (NHW), Black, and Hispanic men and women in the Washington/Hamilton Heights-Inwood Columbia Aging Project who were administered neuropsychological tests of memory, language, and visuospatial abilities at 18- to 24-month intervals for up to 25 years. Multiple-group latent growth curve modeling examined trajectories across sex/gender by race/ethnicity. Results After adjusting for age and education, the largest baseline differences were between NHW men and Hispanic women on visuospatial and language, and between NHW women and Black men on memory. Memory and visuospatial decline was steeper for Black women compared with Hispanic men and NHW women, respectively. Discussion This study takes an important first step in understanding interactions between race/ethnicity and sex/gender on cognitive trajectories by demonstrating variability in sex/gender differences across race/ethnicity.

Introduction The associations between self-reported current and past leisure time physical activity (LTPA) and Alzheimer's disease (AD) incidence were determined using data from the multiethnic Washington/Hamilton Heights-Inwood Columbia Aging Project (WHICAP) study. Methods The metabolic equivalent of LTPA energy expenditure was calculated for self-reported current and past LTPA for 1345 older adults. A Cox proportional hazard model was conducted to estimate the association between LTPA (low, middle, and high) and incident AD risk. Results Comparing high to low level, current and past LTPA were both associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.39 (0.20–0.75) and 0.37 (0.18–0.75), respectively. Compared with "always low," "increased" and "always high" LTPA throughout life were associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.60 (0.36–0.99) and 0.28 (0.08–0.94), respectively. Light- and moderate-intensity LTPA were associated with lower AD risk. Discussion LTPA both throughout life and later in life are associated with lower risk of AD.

Background Cognitive impairment (CI) is estimated to be present in 25%–80% of heart failure (HF) patients, but its prevalence at diagnosis is unclear. To improve our understanding of cognition in HF, we determined the prevalence of CI among adults with incident HF in the REGARDS study. Methods and Results REGARDS is a longitudinal cohort study of adults ≥45 years of age recruited in the years 2003–2007. Incident HF was expert adjudicated. Cognitive function was assessed with the Six-Item Screener. The prevalence of CI among those with incident HF was compared with the prevalence of CI among an age-, sex-, and race-matched cohort without HF. The 436 participants with incident HF had a mean age of 70.3 years (SD 8.9), 47% were female, and 39% were black. Old age, black race, female sex, less education, and anticoagulation use were associated with CI. The prevalence of CI among participants with incident HF (14.9% [95% CI 11.7%–18.6%]) was similar to the non-HF matched cohort (13.4% [11.6%–15.4%]; P Conclusions A total of 14.9% of the adults with incident HF had CI, suggesting that the majority of cognitive decline occurs after HF diagnosis. Increased awareness of CI among newly diagnosed patients and ways to mitigate it in the context of HF management are warranted.

Hypertension is an established risk factor for cognitive decline and dementia in older adults, highlighting the potential importance of antihypertensive treatments in prevention efforts. Work surrounding antihypertensive treatments has suggested possible salutary effects on cognition and neuropathology. Several studies have specifically highlighted renin-angiotensin system drugs, including AT1-receptor blockers and angiotensin-converting-enzyme inhibitors, as potentially benefiting cognition in later life. A small number of studies have further suggested renin-angiotensin system drugs that cross the blood-brain barrier may be linked to lower dementia risk compared to their non-penetrant counterparts. The present meta-analysis sought to evaluate the potential cognitive benefits of blood-brain barrier crossing renin-angiotensin system drugs relative to their non-penetrant counterparts. We harmonized longitudinal participant data from 14 cohorts from 6 countries (Australia, Canada, Germany, Ireland, Japan, United States), for a total of 12,849 individuals at baseline, and assessed for blood-brain barrier crossing potential within antihypertensive medications used by cognitively normal participants. We analyzed seven cognitive domains (attention, executive function, language, verbal memory learning, recall, mental status, and processing speed) using analysis of covariance (adjusted for age, sex, and education) and meta-analyses. Older adults taking blood-brain barrier-crossing renin-angiotensin drugs exhibited better memory recall over up to 3 years of follow-up, relative to those taking non-penetrant medications, despite their relatively higher vascular risk burden. Conversely, those taking non-blood-brain barrier-penetrant medications showed better attention over the same follow-up period, although their lower vascular risk burden may partially explain this result. Findings suggest links between blood-brain barrier crossing renin-angiotensin drugs and less memory decline.

ImportanceExposure to socioeconomic disadvantage is associated with rapid cognitive aging. Biological aging, the progressive loss of system integrity that occurs as we age is proposed as a modifiable process mediating this health inequality.ObjectiveTo test the hypothesis that socioeconomic disparities in cognitive aging in older adults is explained by accelerated biological aging.DesignObservational cohort study.SettingU.S. Health and Retirement Study DNA-methylation sub-study.ParticipantsN=3,648 (49% male) adults aged 50-100 (M=70, SD=10) with DNA methylation data.ExposuresSocioeconomic status (SES) was measured from years of education and household wealth. The extent and pace of biological aging were quantified using three DNA-methylation measures: PhenoAge, GrimAge, and DunedinPoAm.Main Outcomes and MeasuresCognitive aging was measured from repeated longitudinal assessments of immediate and delayed word recall. Latent growth curve modeling estimated participants’ level of memory performance and rate of decline over 2-11 follow-up assessments spanning 2-20 years. Models were estimated to assess whether the relationship between SES and memory trajectories was mediated by biological aging.ResultsOlder adults with lower SES had lower memory performance, faster decline and exhibited accelerated biological aging (SES β=.33, 99% CI[.30-.36], biological-aging measure effect size associations ranged from .08 to .20). Accelerated biological aging was associated with decreased memory performance and faster memory decline (effect-size range .03 to .18). Higher SES was associated with slower biological aging for White and Black men and women, but not Latinx participants. The relationship between biological aging measures and memory was weaker for Black and Latinx participants compared with White people. In mediation analysis, biological aging accounted for 3-9% of the SES-memory gradient in White participants. There was no evidence of mediation in Black or Latinx participants.Conclusions and RelevanceAmong a national sample of older adults, DNA-methylation measures of biological aging were associated with memory trajectories in White, but not Black or Latinx older adults. These results challenge the assumption that DNA-methylation biomarkers of aging that were developed in primarily White people can quantify aging processes affecting cognition in Black and Latinx older adults.

Biological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of eight DNA-methylation and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the United States Health and Retirement Study (HRS; n=9005). We quantified biological aging from four DNA-methylation “clocks” (Horvath, Hannum, PhenoAge, and GrimAge), a DNA-methylation Pace of Aging (DunedinPoAm), and three blood-chemistry measures (PhenoAge, Klemera-Doubal method Biological Age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical-performance tests, self-reported activities of daily living (ADL) limitations and physician-diagnosed chronic diseases, self-rated health, and survival. DNA-methylation and blood-chemistry quantifications of biological aging were moderately correlated (Pearson-r range 0.1-0.4). GrimAge, DunedinPoAm and all three blood-chemistry measures were associated with healthspan characteristics (e.g. mortality effect-size range 1.71-2.32) and showed evidence of more advanced/faster biological aging in Black compared with White participants (Cohen’s d=.4-.5). These measures accounted for 13-95% of Black-White differences in healthspan-related characteristics. Findings that Black Americans are biologically older and aging more rapidly than White Americans of the same chronological age suggest that eliminating disparities in the pace of aging can contribute building to aging health equity.

ObjectiveAlzheimer disease (AD) is a common and costly neurodegenerative disorder. A large proportion of AD risk is heritable, and many genetic risk factors have been identified. The objective of this study was to test the hypothesis that cumulative genetic risk of known AD markers contributed to odds of dementia in a population-based sample.MethodsIn the US population-based Health and Retirement Study (waves 1995–2014), we evaluated the role of cumulative genetic risk of AD, with and without the APOE ε4 alleles, on dementia status (dementia, cognitive impairment without dementia, borderline cognitive impairment without dementia, and cognitively normal). We used logistic regression, accounting for demographic covariates and genetic principal components, and analyses were stratified by European and African genetic ancestry.ResultsIn the European ancestry sample (n = 8,399), both AD polygenic score excluding the APOE genetic region (odds ratio [OR] = 1.10; 95% confidence interval [CI]: 1.00–1.20) and the presence of any APOE ε4 alleles (OR = 2.42; 95% CI: 1.99–2.95) were associated with the odds of dementia relative to normal cognition in a mutually adjusted model. In the African ancestry sample (n = 1,605), the presence of any APOE ε4 alleles was associated with 1.77 (95% CI: 1.20–2.61) times higher odds of dementia, whereas the AD polygenic score excluding the APOE genetic region was not significantly associated with the odds of dementia relative to normal cognition 1.06 (95% CI: 0.97–1.30).ConclusionsCumulative genetic risk of AD and APOE ε4 are both independent predictors of dementia in European ancestry. This study provides important insight into the polygenic nature of dementia and demonstrates the utility of polygenic scores in dementia research.

The Southern dietary pattern, derived within the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, is characterised by high consumption of added fats, fried food, organ meats, processed meats and sugar-sweetened beverages and is associated with increased risk of several chronic diseases. The aim of the present study was to identify characteristics of individuals with high adherence to this dietary pattern. We analysed data from REGARDS, a national cohort of 30 239 black and white adults ≥45 years of age living in the USA. Dietary data were collected using the Block 98 FFQ. Multivariable linear regression was used to calculate standardised beta coefficients across all covariates for the entire sample and stratified by race and region. We included 16 781 participants with complete dietary data. Among these, 34·6 % were black, 45·6 % male, 55·2 % resided in stroke belt region and the average age was 65 years. Black race was the factor with the largest magnitude of association with the Southern dietary pattern (Δ = 0·76 sd, P < 0·0001). Large differences in Southern dietary pattern adherence were observed between black participants and white participants in the stroke belt and non-belt (stroke belt Δ = 0·75 sd, non-belt Δ = 0·77 sd). There was a high consumption of the Southern dietary pattern in the US black population, regardless of other factors, underlying our previous findings showing the substantial contribution of this dietary pattern to racial disparities in incident hypertension and stroke.

Objective To evaluate trials of drugs that target amyloid to determine whether reductions in amyloid levels are likely to improve cognition. Design Instrumental variable meta-analysis. Setting 14 randomized controlled trials of drugs for the prevention or treatment of Alzheimer’s disease that targeted an amyloid mechanism, identified from ClinicalTrials.gov. Population Adults enrolled in randomized controlled trials of amyloid targeting drugs. Inclusion criteria for trials vary, but typically include adults aged 50 years or older with a diagnosis of mild cognitive impairment or Alzheimer’s disease, and amyloid positivity at baseline. Main outcome measures Analyses included trials for which information could be obtained on both change in brain amyloid levels measured with amyloid positron emission tomography and change in at least one cognitive test score reported for each randomization arm. Results Pooled results from the 14 randomized controlled trials were more precise than estimates from any single trial. The pooled estimate for the effect of reducing amyloid levels by 0.1 standardized uptake value ratio units was an improvement in the mini-mental state examination score of 0.03 (95% confidence interval −0.06 to 0.1) points. This study provides a web application that allows for the re-estimation of the results when new data become available and illustrates the magnitude of the new evidence that would be necessary to achieve a pooled estimate supporting the benefit of reducing amyloid levels. Conclusions Pooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.

Key Points Question Does the risk of cognitive decline among US adults vary by sex? Findings In this cohort study using pooled data from 26 088 participants, women, compared with men, had higher baseline performance in global cognition, executive function, and memory. Women, compared with men, had significantly faster declines in global cognition and executive function, but not memory. Meaning These findings suggest that women may have greater cognitive reserve but faster cognitive decline than men., This pooled cohort study used data from 5 population-based cohort studies to investigate whether cognitive decline among US adults varies by sex., Importance Sex differences in dementia risk are unclear, but some studies have found greater risk for women. Objective To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk. Design, Setting, and Participants This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020. Exposure Sex. Main Outcomes and Measures The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P

Background Epidemiological studies utilize residential histories to assess environmental exposure risk. The validity from using commercially-sourced residential histories within national longitudinal studies remains unclear. Our study assessed predictors of non-agreement between baseline addresses from the commercially-sourced LexisNexis database and participants in the national longitudinal study, REasons for Geographic and Racial Differences in Stroke (REGARDS). Additionally, we assessed differences in stroke risk by neighborhood socioeconomic score (nSES) based on participant reported address compared to nSES from LexisNexis/REGARDS matched baseline address. Methods From January 2003–October 2007, REGARDS enrolled 30,239 black and white adults aged 45 and older within the continental United States and collected their baseline address. ArcGIS Desktop 10.5.1 with ESRI 2016 Business Analyst Data was used to geocode baseline addresses from LexisNexis and REGARDS. Logistic regression was used to estimate the likelihood that LexisNexis address matched REGARDS baseline address for each participant. Survival analysis was used to estimate association between nSES and incident stroke. Results Approximately 91% of REGARDS participants had a LexisNexis address. Of these geocoded addresses, 93% of REGARDS baseline addresses matched LexisNexis addresses. Odds of agreement between LexisNexis and REGARDS was higher for older-aged participants (OR = 1.02 per year, 95% CI: 1.01, 1.02), blacks compared to whites (OR = 1.16, 95% CI: 1.05, 1.29), females compared to males (OR = 1.15, 95% CI: 1.04, 1.26), participants with an income of $34k-74k compared to an income less than $20k (OR = 1.62, 95% CI: 1.39, 1.89). Odds of agreement were lower for residents in Midwest compared to residents in the south (OR = 0.82, 95% CI: 0.73, 0.94). No significant differences in nSES-stroke associations were observed between REGARDS only and LexisNexis/REGARDS matched addresses; however, differences in interactions were observed. Conclusion Agreement between LexisNexis and REGARDS addresses varied by sociodemographic groups, potentially introducing bias in studies reliant on LexisNexis alone for residential address data., Highlights • Approximately 9% of REGARDS participants did not have a LexisNexis address history available. • Of participants with both REGARDS and LexisNexis addresses available, 93% of these addresses matched. • Agreement between REGARDS and LexisNexis address varied by socio-demographics—potentially biasing environmental exposures. • Compared to LexisNexis, REGARDS addresses may be valuable in detecting interactions contributing to stroke disparities.

A family history of Alzheimer’s disease (AD) increases risk for AD in an individual by 1.5-to 3-fold. Heritability of AD risk may be due in part to the aggregation of neurodegeneration and cerebrovascular changes with cognitive endophenotypes within families. The purpose of this study was to determine the extent to which cognitive functioning in middle-aged adults is associated with objectively-measured neurodegenerative and cerebrovascular neuroimaging markers linked to risk for clinical AD in their parents, and the extent to which these associations differ by race/ethnicity and language, as proxy variables for social advantage. Middle-aged children enrolled in the Offspring study (n=356; 53.1±10.1 years old; 13% Non-Hispanic White, 27% Non-Hispanic Black, 26% Latinx tested in English, 34% Latinx tested in Spanish; 65% women; 13.5±3.4 years education) were administered the NIH Toolbox, a computerized neuropsychological battery, in their preferred language. Older adults were a subset of the Washington-Heights Inwood Columbia Aging Project (77.3±6.6 years old; 75% women; 10.0±4.6 years education) who underwent T1w- and T2w-MRI and who had a child enrolled in the Offspring study. We tested the associations of parental MRI measures reflecting neurodegeneration (hippocampal volume, cortical thickness) and cerebrovascular disease (white matter hyperintensity (WMH) volume, presence of infarct) with cognitive tests scores in Offspring participants. We further stratified the models by race/ethnicity. Better offspring cognitive scores aggregated lower parental neurodegeneration and cerebrovascular disease among Non-Hispanic White and Latinx participants, and with lower parental cerebrovascular disease alone among Non-Hispanic Black participants. Associations were generally strongest in Non-Hispanic White participants compared to the other groups. These results suggest a more consistent link between offspring cognitive endophenotype and parental brain health in intergenerational AD transmission among Non-Hispanic White participants compared to racial/ethnic and minority groups in which other social factors may be adding variance.

INTRODUCTIONNumerous neuroimaging studies demonstrated racial and ethnic disparities in brain health at older ages. It remains unclear whether racial and ethnic disparities increase with aging and whether they are already apparent in midlife.METHODSWe investigated differences in MRI markers of aging and cerebrovascular disease in 969 participants from the Washington Heights-Inwood Columbia Aging Project (WHICAP; mean age: 75 years) and 496 participants from the Offspring study (mean age: 55 years) across race and ethnicity (white, Black, Latinx).RESULTSOlder whites had greater cortical thickness compared with Latinxs, who also had greater thickness than Blacks. Cortical thickness was similar across race in the middle-aged cohort. Regarding white matter hyperintensity (WMH) volume, Blacks had disproportionately greater WMH volume compared to both whites and Latinxs at older ages. Racial disparities are already apparent in midlife, where Blacks have disproportionately greater WMH than whites.DiscussionThese findings suggest that racial disparities in WMH volume are already apparent in midlife.

Introduction Low vitamin D intake and low vitamin D circulating levels have been associated with increased risk for dementia. We aimed to examine the association between vitamin D intake and dementia in a multiethnic cohort. Methods A longitudinal study of 1759 non-demented older (≥65 years) participants of the Washington Heights-Inwood Columbia Aging Project with follow-up visits and completed a food frequency questionnaire. Dementia was diagnosed by consensus using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Cox hazard regression was performed. Results During a mean follow-up of 5.8 years, 329 participants developed dementia. Participants with the highest tertile of vitamin D intake from food sources had decreased risk (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.54-0.97, P = .030) for dementia compared with those with the lowest tertile, adjusting for age, sex, race/ethnicity, education, apolipoprotein E (APOE)-e4, physical activity, Mediterranean diet (MeDI) score, income, depression, hypertension, diabetes, cardiovascular disease, and smoking. Discussion Higher vitamin D intake is associated with decreased risk of dementia in a multiethnic cohort.

IntroductionBlood-based Alzheimer’s disease (AD) biomarkers provide opportunities for community studies and across ethnic groups. We investigated blood biomarker concentrations in the Washington Heights, Inwood, Columbia Aging Project (WHICAP), a multi-ethnic community study of aging and dementia.MethodsWe measured plasma Aβ40, Aβ42,T-tau, P-tau181 and P-tau217, and neurofilament light chain (NfL) in 113 autopsied participants, (29% with high AD neuropathological changes) and in 300 clinically evaluated individuals (42% with clinical AD). Receiver operating characteristics were used to evaluate each biomarker. We also investigated biomarkers as predictors of incident clinical AD.ResultsP-tau181, P-tau217 and NfL concentrations were elevated in pathologically and clinically diagnosed AD. Decreased Aβ42/Aβ40 ratio and increased P-tau217 and P-tau181 were associated with subsequent AD diagnosis.DiscussionBlood-based AD biomarker concentrations are associated with pathological and clinical diagnoses and can predict future development of clinical AD, providing evidence that they can be incorporated into multi-ethnic, community-based studies.

INTRODUCTIONLate-onset Alzheimer’s disease (AD) frequently co-occurs with cerebrovascular disease. We hypothesized that interactions between genes and cerebrovascular risk factors (CVRFs) contribute to AD risk.METHODSParticipants age 65 years or older from five multi-ethnic cohorts (N=14,669) were included in genome-wide association meta-analyses for AD including an interaction factor for a CVRF score created from body mass index, hypertension, heart disease, and diabetes. Significant gene level results were substantiated using neuropathological and gene expression data.RESULTSAt the gene-level, FMNL2 interacted with the CVRF score to significantly modify AD risk (p= 7.7×10-7). A SNP within FRMD4B, rs1498837, was nominally significant (p=7.95×10-7). Increased FMNL2 expression was significantly associated with brain infarcts and AD.DISCUSSIONFMNL2 is highly expressed in the brain and has been associated with ischemic stroke and failures in endosomal trafficking, a major pathway in AD pathology. The results highlight an interaction between FMNL2 and CVRFs on AD susceptibility.

Background/objectives Given the lack of effective pharmacologic strategies to prevent, slow, or reverse dementia progression, maximizing quality of life (QOL) is a major priority for persons living with dementia. Despite well-documented racial/ethnic disparities in dementia incidence and prevalence, it is unknown whether there are racial/ethnic disparities in QOL among persons with dementia. The objective of this study was to determine if there are racial/ethnic differences in poor health-related quality of life (HRQOL) among persons with and without dementia in a nationally-representative cohort. Design Repeated measures cross-sectional analysis of a prospective cohort study. Setting United States nationally-representative National Health and Aging Trends Study (2011-2018). Participants Non-nursing home-dwelling Black, Latino, and white adults age 65+ (n = 10,886). Measurements We estimated racial/ethnic differences in five dichotomous indicators of poor HRQOL (depressive and anxiety symptoms, self-rated health, pain, and physical functional limitations), stratified by dementia status (probable, possible, none). We used generalized estimating equations to estimate prevalence ratios (PRs) and differences, and marginal standardization to estimate prevalence. Results Generally, Blacks and Latinos reported higher prevalence of poor HRQOL compared with whites. The largest differences were observed for self-rated health, and Latino-white differences were slightly larger compared to Black-white differences. PRs were larger among those with no dementia. For example, the Black versus white PRs for poor self-rated health were 1.93 (95% confidence interval (CI) = 1.82-2.04) among the no dementia group and 1.21 (95% CI = 1.12-1.31) among the probable dementia group; Latino versus white PRs for these comparisons were 2.39 (2.21-2.59) and 1.48 (1.35-1.62), respectively. Prevalence differences also showed racial/ethnic differences, but these were similar across dementia statuses. Conclusions We observed racial/ethnic disparities in poor HRQOL, showing greater unmet clinical needs among Black and Latino versus white older adults. Relative disparities were smaller in those with dementia, but absolute magnitudes of disparities were similar by dementia status.

The Washington University School of Medicine Knight Alzheimer Disease Research Center's "African American Participation in Alzheimer Disease Research: Effective Strategies" Workshop convened to address a major limitation of the ongoing scientific progress regarding Alzheimer's disease and related dementias (ADRD): participants in most ADRD research programs overwhelmingly have been limited to non-Hispanic white persons, thus precluding knowledge as to how ADRD may be represented in non-white individuals. Factors that may contribute to successful recruitment and retention of African Americans into ADRD research were discussed and organized into actionable next steps as described within this report.