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To describe a cultural neuropsychological approach to prestatistical harmonization of cognitive data across the United States (U.S.) and Mexico with the Harmonized Cognitive Assessment Protocol (HCAP).We performed a comprehensive review of the administration, scoring, and coding procedures for each cognitive test item administered across the English and Spanish versions of the HCAP in the Health and Retirement Study (HRS) in the U.S. and the Ancillary Study on Cognitive Aging in Mexico (Mex-Cog). For items that were potentially equivalent across studies, we compared each cognitive test item for linguistic and cultural equivalence and classified items as confident or tentative linking items, based on the degree of confidence in their comparability across cohorts and language groups. We evaluated these classifications using differential item functioning techniques.We evaluated 132 test items among 21 cognitive instruments in the HCAP across the HRS and Mex-Cog. We identified 72 confident linking items, 46 tentative linking items, and 14 items that were not comparable across cohorts. Measurement invariance analysis revealed that 64% of the confident linking items and 83% of the tentative linking items showed statistical evidence of measurement differences across cohorts.Prestatistical harmonization of cognitive data, performed by a multidisciplinary and multilingual team including cultural neuropsychologists, can identify differences in cognitive construct measurement across languages and cultures that may not be identified by statistical procedures alone. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objectives Telephone-administered cognitive assessments are a cost-effective and sometimes necessary alternative to face-to-face assessments. There is limited information in large studies concerning mode effects, or differences in cognition attributable to the assessment method, as a potential measurement threat. We evaluated mode effects on cognitive scores using a population-based sample of community-living older adults. Methods We used data from participants aged 65–79 in the 2014 Health and Retirement Study for whom the interview mode was randomized (n = 6,825). We assessed mode differences in test means, whether mode modifies associations of cognition with criterion variables, and formal measurement invariance testing. Results Relative to face-to-face assessment, telephone assessment was associated with higher scores for memory and calculation (0.06 to 0.013 standard deviations [SD]) and lower scores for nonmemory items (−0.09 to −0.01 SD). Cognition was significantly differentially related to instrumental activities of daily living difficulty depending on assessment mode. Measurement invariance testing identified evidence of mode differences in certain tests as a function of mode: adjusting for underlying cognition, the largest mode differences in memory and attention: immediate noun recall, delayed word recall, and serial-7s scores were higher given telephone administration. Discussion Differences by mode of administration are apparent in cognitive measurement in older adults, albeit to a small degree in our study, and most pronounced for tests of memory and attention. The importance of accounting for mode differences ultimately depends on one’s research question and study sample: not all associations may be affected by mode differences, and such modification may only be apparent among those with lower cognitive functioning.

We characterized the additive contribution of cerebrovascular biomarkers to amyloid and neurodegeneration biomarkers (AV(N)) when modeling prospective, longitudinal cognitive trajectories within 3 major racial/ethnic groups. Participants (n = 172; age = 69–96 years; 62% women; 31%/49%/20% Non–Hispanic White/Non–Hispanic Black/Hispanic) from the Washington Heights-Inwood Columbia Aging Project were assessed for amyloid (Florbetaben PET), neurodegeneration (cortical thickness, hippocampal volume), and cerebrovascular disease (white matter hyperintensity (WMH), infarcts). Neuropsychological assessments occurred every 2.3 ± 0.6 years for up to 6 visits (follow-up time: 4.2 ± 3.2 years). Linear mixed-effects models were stratified by race/ethnicity groups. Higher amyloid was associated with faster memory decline in all 3 racial/ethnic groups, but was related to faster cognitive decline beyond memory in minoritized racial/ethnic groups. Higher WMH was associated with faster language, processing speed/executive function, and visuospatial ability decline in Non–Hispanic Black participants, while infarcts were associated with faster processing speed/executive function decline in Non–Hispanic White participants. Complementary information from AD, neurodegenerative, and cerebrovascular biomarkers explain decline in multiple cognitive domains, which may differ within each racial/ethnic group. Importantly, treatment strategies exist to minimize vascular contributions to cognitive decline.

Alzheimer’s disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, gene by CVRF interaction analyses for AD, in 6568 patients and 8101 controls identified FMNL2 (p = 6.6 × 10–7). A significant increase in FMNL2 expression was observed in the brains of patients with brain infarcts and AD pathology and was associated with amyloid and phosphorylated tau deposition. FMNL2 was also prominent in astroglia in AD among those with cerebrovascular pathology. Amyloid toxicity in zebrafish increased fmnl2a expression in astroglia with detachment of astroglial end feet from blood vessels. Knockdown of fmnl2a prevented gliovascular remodeling, reduced microglial activity and enhanced amyloidosis. APP/PS1dE9 AD mice also displayed increased Fmnl2 expression and reduced the gliovascular contacts independent of the gliotic response. Based on this work, we propose that FMNL2 regulates pathology-dependent plasticity of the blood–brain-barrier by controlling gliovascular interactions and stimulating the clearance of extracellular aggregates. Therefore, in AD cerebrovascular risk factors promote cerebrovascular pathology which in turn, interacts with FMNL2 altering the normal astroglial-vascular mechanisms underlying the clearance of amyloid and tau increasing their deposition in brain.

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.

Introduction: Long-term neurological consequences (eg, stroke, impaired cognition) have been linked to SARS-CoV-2 infection and severity. There are limited data from studies with racial, ethnic, socioeconomic, and geographic diversity. C4R is a prospective study of adults from 14 cohorts that aims to link pre-COVID phenotyping, including cognition (8 studies), to COVID related illness and sequelae. We aimed to conduct pre-statistical harmonization of cognitive tests administered in English and Spanish from 8 cohorts: ARIC, CARDIA, FHS, HCHS/SOL-INCA, MESA, NOMAS, REGARDS, and SHS (Table). Methods: We conducted extensive item-level review of administration, scoring, and coding procedures and score distributions for 84 tests administered in English (all studies) and Spanish (NOMAS, MESA, HCHS/SOL-INCA). Results: Orientation to time and 3-word registration and recall spanned all studies and both languages. Word list recall and verbal fluency (animal; letter) spanned 7 studies (Table). There was variability in the structure, content, administration, scoring, and data coding procedures for items across cohorts and between Spanish and English. Word lists varied by number of words (9-16) and learning trials (3-5). Animal naming varied by time (30 vs. 60 seconds), animal type (4-legged vs. any animal), and scoring (allowing mythical/imaginary animals). Letter fluency varied by whether both Spanish and English words were permitted. Other tests differed by version, study-specific adaptations, prompts/cues, and specificity of scoring rules across cohorts. Conclusions: Cognitive test harmonization requires detailed review of administration, scoring, coding, translation, and procedural differences. Accounting for this variability is essential to cognitive data interpretation. Our pre-statistical harmonization will inform data augmentation and formal harmonization to yield harmonized measures of cognition to clarify population-level differences in cognitive outcomes linked to SARS-CoV-2 infection.

BackgroundBrain arterial diameters are novel imaging biomarkers of cerebrovascular disease, cognitive decline and dementia. Traditional vascular risk factors have been associated with brain arterial diameters but whether there may be genetic determinants of brain arterial diameters is unknown.ResultsWe studied 4150 participants from six geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). We measured brain arterial diameters for 13 segments and averaged them to obtain a global measure of brain arterial diameters as well as the posterior and anterior circulations. A genome-wide association study (GWAS) revealed 14 variants at one locus associated with global brain arterial diameter at genome-wide significance (P−8) (top SNP, rs7921574; β =0.06, P=1.54×10−8). This locus mapped to an intron ofCNNM2. A trans-ancestry GWAS meta-analysis identified two more loci atNT5C2(rs10748839; P=2.54×10−8) and atAS3MT(rs10786721; P=4.97×10−8), associated with global brain arterial diameter. In addition, two SNPs co-localized with expression ofCNNM2(rs7897654, β=0.12, P=6.17×10−7) andAL356608.1(rs10786719, β =-0.17, P=6.60×10−6) in brain tissue. For the posterior brain arterial diameter, two variants at one locus mapped to an intron ofTCF25were identified (top SNP, rs35994878; β =0.11, P=2.94×10−8). For the anterior brain arterial diameter, one locus atADAP1was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10−8).ConclusionOur study reveals three novel risk loci (CNNM2, NT5C2 and AS3MT) associated with brain arterial diameters. Our finding may elucidate the mechanisms by which brain arterial diameters influence the risk of stroke and dementia.

Background: A history of pregnancy-induced hypertension (PIH) is associated with higher risk of developing cerebrovascular disease. Data are lacking on the relationship between PIH, chronic hypertension, and MRI markers of cerebral small vessel disease (CSVD) in older people. Methods: We recruited parous individuals without dementia from the Northern Manhattan Study and the Washington Heights-Inwood Washington Heights-Hamilton Heights-Inwood Columbia Aging Project, two long-running prospective cohort studies in New York City. Detailed obstetric and medical histories were obtained by interview. We defined history of PIH as self-report of at least one pregnancy complicated by gestational hypertension, preeclampsia or eclampsia. We categorized participants as having no hypertension, current hypertension without history of PIH, or current hypertension with history of PIH. Number and location of infarcts and white matter hyperintensity (WMH) volume was assessed by MRI. We used generalized linear models to compare imaging outcomes between groups, adjusting for demographics and cardiovascular risk factors. To account for the effects of early onset hypertension, we performed a sensitivity analysis in NOMAS participants only, adjusting for hypertension as a time varying covariate. Results: A total of 221 participants were interviewed (mean age 69 years [SD 7.5]; 22% white, 28% non-Hispanic Black, 48% Hispanic) of whom 128 (58%) had current hypertension without history of PIH, and 16 (7%) had current hypertension with history of PIH. Adjusting for covariates, hypertensive participants with a history of PIH had higher WMH volume, but no difference in deep silent brain infarcts (Table). Conclusions: In a multiethnic cohort of older parous individuals, those with hypertension and a history of PIH had the highest volume of WMH, suggesting a higher burden of CSVD.

Objective: To compare longitudinal verbal fluency performance among Latinx Spanish speakers who develop Alzheimer’s disease to those who do not develop dementia in absolute number of words produced on each task and their ratio to combine both scores. Method: Participants included 833 Latinx Spanish-speaking older adults from a community-based prospective cohort in Manhattan. We performed growth curve modeling to investigate the trajectories of letter and semantic fluency, and their ratio (i.e., ‘semantic index’), between individuals who developed Alzheimer’s disease and those who did not (i.e., controls). The semantic index quantifies the proportion of words generated for semantic fluency in relation to the total verbal fluency performance. Results: Letter fluency performance did not decline in controls; we observed a linear decline in those who developed Alzheimer’s disease. Semantic fluency declined in both groups and showed an increased rate of change over time in the incident Alzheimer’s disease group; in comparison, the control group had a linear and slower decline. There were no group differences in the longitudinal trajectory (intercept and slope) of the semantic index. Conclusion: A decline in letter fluency and a more rapid and accelerating decline over time in semantic fluency distinguished people who developed Alzheimer’s disease from controls. Using the semantic index was not a superior marker of incident Alzheimer’s disease compared to examining the two fluency scores individually. Results suggest the differential decline in verbal fluency tasks, when evaluated appropriately, may be useful for early identification of Alzheimer’s disease in Latinx Spanish speakers, a historically understudied population.

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.

Long-term exposure to air pollution has been associated with changes in levels of several metabolites measured in the peripheral blood. However, most work has been conducted in ethnically homogenous populations. We studied the relationship between the plasma metabolome and long-term exposure to three air pollutants: particulate matter (PM) less than 2.5 µm in aero diameter (PM2.5), PM less than 10 µm in aero diameter (PM10) and nitrogen dioxide (NO2) among 107 participants of the Washington Heights and Inwood Community Aging Project (WHICAP) in New York City. Plasma metabolomic profiles were generated using untargeted liquid chromatography coupled with high-resolution mass spectrometry. We estimated the association between each metabolic feature and predicted annual mean exposure to the air pollutants using three approaches: 1. A metabolome wide association study (MWAS) framework; 2. Feature selection using elastic net regression; and 3. A multivariate approach using partial least squares discriminant analysis. Additionally, we identified the pathways enriched by metabolic features associated with exposure through pathway analysis. The samples were collected from 1995 – 2015 and included non-Hispanic white, Caribbean Hispanic, and non-Hispanic Black older adults. Through the MWAS, we found 79 features associated with exposure to PM2.5(false discovery rate at 5%) but none associated with PM10or NO2. Pathway analysis revealed that PM2.5exposure was associated with altered amino acid metabolism, energy production, and oxidative stress response. Six features were found to be associated with PM2.5exposure through all three approaches, annotated as: cysteinylglycine disulfide, a diglyceride, and a dicarboxylic acid. Additionally, we found that the relationship between several features and PM2.5exposure was modified by diet and metabolic diseases. These signals, identified in a neighborhood-representative older population, could help understand the mechanisms through which PM2.5exposure can lead to altered metabolic outcomes in an older population.HIGHLIGHTSLong-term exposure to PM2.5is associated with altered plasma metabolic features in an aging populationThese associations are modified by a dementia diagnosis, history of diabetes, APOE-ε4 allele, and dietPathways related to energy production, amino acid metabolism, and redox homeostasis are associated with exposure to PM2.5GRAPHICAL ABSTRACT

Routine healthcare visits offer the opportunity to screen older adults for cognitive changes that accompany the earliest clinical stages of Alzheimer's disease (AD) including Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). It is well-established that women are at increased risk for AD and that many women see their gynecologist as their primary care doctor. Given this unique relationship, the Women's Preventive Services Initiative and the American College of Obstetrics and Gynecology now advocate for integrated care of women at all ages. Memory screening of older women should be paramount in this effort. Research is needed to determine which screening tools are most effective and practical. Here we assess the feasibility and utility of a subjective memory screener at the well-woman visit.Women aged 60 and above completed a 5-item screener at their well-woman visit at the Columbia University Integrated Women's Health Center (Table 1). Women who endorsed any item were considered to have a positive screen and were given the option to pursue clinical evaluation for memory concerns through the Division of Aging and Dementia.Only 8 of 354 women declined to complete the screener. Of the completed screeners, 16% (n = 56) were positive. The most frequently endorsed item was difficulty with memory or thinking compared to others the same age (8%, n = 28) (See Table 1). 44% (n = 24) of women with positive screens pursued referral, and six have been seen to date. One woman was diagnosed with MCI. Clinical impressions of the remainder were unremarkable. All six cases had family history of dementia or memory problems.The well-woman visit provides a key opportunity to routinely screen older women for early indicators of AD and treatable causes of cognitive impairment. Preliminary results support the feasibility and value of such screening as part of a comprehensive well-woman program. Early identification of women experiencing SCD will enable investigation into the cause of their memory concerns, and longitudinal monitoring of cognitive change. Future work should evaluate the added value of an objective cognitive screen to complement SCD screening and identify women who may benefit from further evaluation.

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: This study aimed to investigate the association between dietary prebiotic intake and risk for Alzheimer’s disease (AD). Methods: This longitudinal study includes 1,837 elderly (≥65 years) participants of a multi-ethnic community-based cohort study who were dementia-free at baseline and had provided dietary information from food frequency questionnaires. Total daily intake of fructan, one of the best-known prebiotics, was calculated based on consumption frequency and fructan content per serving of 8 food items. The associations of daily fructan intake with AD risk were examined using a Cox proportional hazards model, adjusted for cohort recruitment wave, age, gender, race/ethnicity, education, daily caloric intake, and APOE genotype. Effect modification by race/ethnicity, APOE genotype, and gender was tested by including an interaction term into the Cox models, as well as by stratified analyses. Results: Among 1,837 participants (1,263 women [69%]; mean [SD] age = 76 [6.3] years), there were 391 incident AD cases during a mean follow-up of 7.5 years (13736 person-years). Each additional gram of fructan intake was associated with 24% lower risk for AD ((95% CI)=0.60-0.97; P =0.03). Additional adjusting for smoking, alcohol consumption, and comorbidity index did not change results materially. The associations were not modified by race/ethnicity, gender, and APOE genotype, although stratified analyses showed that fructan intake was significantly associated with reduced AD risk in Hispanics but not in non-Hispanic Blacks or Whites. Conclusion: Higher dietary fructan intake is associated with a reduced risk of clinical Alzheimer’s disease among older adults.

BACKGROUND AND OBJECTIVES: This prospective study seeks to examine the utility of subjective cognitive decline (SCD) as a marker of future progression to dementia in a community-based cohort of non-Latinx White, non-Latinx Black, and Latinx individuals. Debate surrounds the utility of SCD, the subjective perception of decline in one's cognition before such impairment is evident in traditional neuropsychological assessments, as an early indicator of impending Alzheimer disease. Unfortunately, most studies examining SCD have been conducted in non-Latinx White samples and commonly exclude groups of individuals shown to be most vulnerable to dementia. METHODS: Participants were enrolled into this cohort study from the Washington Heights–Inwood Columbia Aging Project if they were cognitively unimpaired, had baseline measurement of SCD, and self-identified as non-Latinx White, non-Latinx Black, or Latinx. SCD was measured as a continuous sum of 10 items assessing cognitive complaints. Competing risk models tested the main effects of baseline SCD on progression to dementia. Models were adjusted for age, sex/gender, years of education, medical comorbidity burden, enrollment cohort, and baseline memory test performance with death jointly modelled as a function of race/ethnicity. RESULTS: A total of 4,043 (1,063 non-Latinx White, 1,267 non-Latinx Black, and 1,713 Latinx) participants were selected for this study with a mean age of 75 years, 67% women, and with a mean follow-up of 5 years. Higher baseline SCD was associated with increased rates of incident dementia over time in the full sample (hazard ratio [HR] 1.085, CI 1.047–1.125, p < 0.001) and within Latinx (HR 1.084, CI 1.039–1.130, p < 0.001) and non-Latinx Black individuals (HR 1.099, CI 1.012–1.194, p = 0.024). DISCUSSION: Overall results of this study support SCD as a prodromal marker of dementia in a multiracial community sample, and in Latinx and non-Latinx Black individuals in particular. Because models examining the risk of dementia were adjusted for baseline memory test performance, the results support the idea that SCD, a subjective reflection of one's own current cognitive functioning, contributes information above and beyond standard memory testing. Current findings highlight the importance of carefully evaluating any memory concerns raised by older adults during routine visits and underscore the potential utility of screening older adults for SCD.

Background and Objectives:Exposure to socioeconomic disadvantage is associated with early-onset 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. We examined whether socioeconomic disparities in cognitive aging in mid-to late-life adults is explained by accelerated biological aging similarly across race, ethnicity and sex/gender.Methods:Data was from a prospective cohort study of the U.S. Health and Retirement Study DNA-methylation sub-study. Socioeconomic status (SES) was measured from years of education and household wealth at baseline. The extent and pace of biological aging were quantified using three DNA-methylation measures: PhenoAge, GrimAge, and DunedinPoAm. Cognitive 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. Multiple-group models were estimated to assess whether the relationship between SES and memory trajectories was mediated by biological aging across racial-ethnic by sex/gender subgroups.Results:Data from a total of 3,997 adults aged 50-100 were analyzed. Participants with lower SES had lower memory performance, faster decline and exhibited accelerated biological aging (SES effect size associations (β) ranged from .08 to .41). Accelerated biological aging was associated with decreased memory performance and faster memory decline (effect-size range .03 to .23). SES-biological aging associations were strongest for White men and women and weakest for Latinx women. The relationship between biological aging measures and memory was weaker for Black participants compared with White and Latinx people. In mediation analysis, biological aging accounted for 4-27% of the SES-memory gradient in White participants. There was little evidence of mediation in Black or Latinx participants.Discussion:Among a national sample of mid-to late-life adults, DNA-methylation measures of biological aging were variably associated with memory trajectories and SES across White, Black, and Latinx mid-to late-life adults. These results challenge the assumption that DNA-methylation biomarkers of aging that were developed in primarily White people can equivalently quantify aging processes affecting cognition in Black and Latinx mid-to late-life adults.

Meaningful reductions in racial and ethnic inequities in chronic diseases of aging remain unlikely without major advancements in the inclusion of minoritized populations in aging research. While sparse, studies investigating research participation disparities have predominantly focused on individual-level factors and behavioral change, overlooking the influence of study design, structural factors, and social determinants of health on participation. This is also reflected in conventional practices that consistently fail to address established participation barriers, such as study requirements that impose financial, transportation, linguistic, and/or logistical barriers that disproportionately burden participants belonging to minoritized populations. These shortcomings not only risk exacerbating distrust toward research and researchers, but also introduce significant selection biases, diminishing our ability to detect differential mechanisms of risk, resilience, and response to interventions across subpopulations. This forum article examines the intersecting factors that drive both health inequities in aging and disparate participation in aging research among minoritized populations. Using an intersectional, social justice, and emancipatory lens, we characterize the role of social determinants, historical contexts, and contemporaneous structures in shaping research accessibility and inclusion. We also introduce frameworks to accelerate transformative theoretical approaches to fostering equitable inclusion of minoritized populations in aging research.

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: Prior research suggests that the strength of association between Alzheimer’s disease pathology and lower cognitive performance is influenced by modifiable psychosocial factors, such as social network size. However, little is known about distinct social relationship types. METHODS: The current cross-sectional study used data from the Washington Heights-Inwood Columbia Aging Project to examine whether social network characteristics (i.e., total size, spouse/partner, number of children, other relatives, friends) moderate associations between cortical thickness in regions implicated in Alzheimer’s disease and cognitive performance. RESULTS: Lower cortical thickness was associated with worse global cognition among individuals with smaller friend networks, but not among individuals with larger friend networks. This pattern of results was most prominent for language and speed/executive functioning. DISCUSSION: Longitudinal and intervention studies are needed to determine whether these cross-sectional findings reflect a protective effect of later-life friendships for maintaining cognitive performance in the context of poorer brain health.

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.

Objective: Racial/ethnic disparities in cognitive aging are only partly attributable to socioeconomic indicators. Psychosocial factors, such as discrimination and perceived control, also differ across racial/ethnic groups, and emerging literature highlights their potential role in contributing to cognitive disparities in addition to socioeconomic status. Method: 1,463 older adults (51% Hispanic, 27% non-Hispanic Black, and 22% non-Hispanic White) in the Washington Heights-Inwood Columbia Aging Project completed cognitive and psychosocial measures, including a comprehensive neuropsychological battery, Everyday and Major Experiences of Lifetime Discrimination scales, and the Perceived Control scale. Mediation models quantified separate indirect effects of Black race and Hispanic ethnicity on global cognitive composite scores through education, income, discrimination, and external perceived control. Results: Educational attainment, income, and perceived control each mediated racial/ethnic disparities in global cognition. Socioeconomic indicators (i.e., lower education and lower income) explained approximately 50% of the Black-White and Hispanic-White disparities in global cognition, and more external perceived control explained an additional 5%-8%. Hispanics reported the lowest levels of discrimination, while non-Hispanic Blacks reported the highest levels. However, neither everyday nor major lifetime discrimination was associated with global cognition. Significant racial/ethnic disparities in global cognition remained after accounting for the included socioeconomic and psychosocial factors. Conclusions: This study suggests that psychosocial factors may explain racial/ethnic disparities in cognitive aging above and beyond socioeconomic indicators. More external perceived control, which could reflect chronic exposure to interpersonal and institutional marginalization, may be a particularly salient psychosocial risk factor for poorer cognitive aging among non-Hispanic Black and Hispanic older adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

ImportancePerceived stress can have long-term physiological and psychological consequences and has shown to be a modifiable risk factor for Alzheimer disease and related dementias.ObjectiveTo investigate the association between perceived stress and cognitive impairment in a large cohort study of Black and White participants aged 45 years or older.Design, Setting, and ParticipantsThe Reasons for Geographic and Racial Differences in Stroke (REGARDS) study is a national population-based cohort of 30 239 Black and White participants aged 45 years or older, sampled from the US population. Participants were recruited from 2003 to 2007, with ongoing annual follow-up. Data were collected by telephone, self-administered questionnaires, and an in-home examination. Statistical analysis was performed from May 2021 to March 2022.ExposuresPerceived stress was measured using the 4-item version of the Cohen Perceived Stress Scale. It was assessed at the baseline visit and during 1 follow-up visit.Main Outcomes and MeasuresCognitive function was assessed with the Six-Item Screener (SIS); participants with a score below 5 were considered to have cognitive impairment. Incident cognitive impairment was defined as a shift from intact cognition (SIS score >4) at the first assessment to impaired cognition (SIS score ≤4) at the latest available assessment.ResultsThe final analytical sample included 24 448 participants (14 646 women [59.9%]; median age, 64 years [range, 45-98 years]; 10 177 Black participants [41.6%] and 14 271 White participants [58.4%]). A total of 5589 participants (22.9%) reported elevated levels of stress. Elevated levels of perceived stress (dichotomized as low stress vs elevated stress) were associated with 1.37 times higher odds of poor cognition after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (adjusted odds ratio [AOR], 1.37; 95% CI, 1.22-1.53). The association of the change in the Perceived Stress Scale score with incident cognitive impairment was significant in both the unadjusted model (OR, 1.62; 95% CI, 1.46-1.80) and after adjustment for sociodemographic variables, cardiovascular risk factors, and depression (AOR, 1.39; 95% CI, 1.22-1.58). There was no interaction with age, race, and sex.Conclusions and RelevanceThis study suggests that there is an independent association between perceived stress and both prevalent and incident cognitive impairment. The findings suggest the need for regular screening and targeted interventions for stress among older adults.

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.

Objective:Stress is a risk factor for numerous negative health outcomes, including cognitive impairment in late-life. The negative association between stress and cognition may be mediated by depressive symptoms, which separate studies have identified as both a consequence of perceived stress and a risk factor for cognitive decline. Pathways linking perceived stress, depressive symptoms, and cognition may be moderated by sociodemographics and psychosocial resources. The goal of this cross-sectional study was to identify modifying factors and enhance understanding of the mechanisms underlying the stress–cognition association in a racially and ethnically diverse sample of older adults.Method:A linear regression estimated the association between perceived stress and episodic memory in 578 older adults (Mage = 74.58) in the Washington Heights-Inwood Columbia Aging Project. Subsequent models tested whether depressive symptoms mediated the stress–memory relationship and whether sociodemographics (gender, race, and ethnicity) or perceived control moderated these pathways.Results:Independent of sociodemographics and chronic diseases, greater perceived stress was associated with worse episodic memory. This relationship was mediated by more depressive symptoms. Higher perceived control buffered the association between stress and depressive symptoms. There was no significant moderation by gender, race, or ethnicity.Conclusion:Depressive symptoms may play a role in the negative association between perceived stress and cognition among older adults; however, longitudinal analyses and studies using experimental designs are needed. Perceived control is a modifiable psychological resource that may offset the negative impact of stress.

Strategies to prevent or delay Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) are urgently needed. Blood pressure (BP) management is a promising strategy for AD/ADRD prevention and the key element in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet the effects of different population level BP control strategies across the life course on AD/ADRD are not known.Large-scale randomized controlled trials are the least biased approach to identifying the effect of BP control on AD/ADRD, yet trials may be infeasible due to the need for prolonged follow-up and very large sample sizes. Thus, simulation analyses leveraging the best available observational data may be the best and most practical approach to answering these questions.In this manuscript, we describe the design principles, implementation details, and population-level validation of a novel population health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP COG) study of the effect of BP levels over the life course on cognitive decline and dementia.MICROSIM was designed by applying computer programming best practices to create a novel simulation model. The initial purpose of this extensible, open-source framework is to explore a series of questions related to the impact of different blood pressure management strategies on late-life cognition and all-cause dementia, as well as the effects on race differences in all-cause dementia incidence. Ultimately, though, the framework is designed to be extensible such that a variety of different clinical conditions could be added to the framework.