IMPORTANCE Small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH), is associated with cognitive decline and risk of clinical Alzheimer disease (AD). One way in which small vessel cerebrovascular disease could contribute to AD is through the promotion of neurodegeneration; the effect of small vessel cerebrovascular disease on neurodegeneration may differ across racial and ethnic groups. OBJECTIVE To examine whether WMH volume is associated with cortical thinning over time and subsequent memory functioning and whether the association between WMH volume and cortical thinning differs among racial and ethnic groups. DESIGN, SETTING, AND PARTICIPANTSThis longitudinal community-based cohort study included older adults from northern Manhattan who were participants in the Washington Heights-Inwood Columbia Aging Project. Participants underwent two 3T magnetic resonance imaging (MRI) scans a mean of 4 years apart. Data were collected from March 2011 to January 2020.EXPOSURES Total and regional WMH volumes. MAIN OUTCOMES AND MEASURESThe association of total and regional WMH volumes with cortical thinning over time was tested using general linear models in a vertexwise analysis. Cortical thinning was measured vertexwise by symmetrized percent change between 2 time points. The association of changes in cortical thickness with memory and whether this association differed by race and ethnicity was also analyzed. Delayed memory was a secondary outcome. RESULTSIn 303 participants (mean [SD] age, 73.16 [5.19] years, 181 [60%] women, 96 [32%] non-Hispanic White, 113 [37%] Non-Hispanic Black, 94 [31%] Hispanic), baseline WMH volumes were associated with cortical thinning in medial temporal and frontal/parietal regions. Specifically, total WMH volume was associated with cortical thinning in the right caudal middle frontal cortex (P = .001) and paracentral cortex (P = .04), whereas parietal WMH volume was associated with atrophy in the left entorhinal cortex (P = .03) and right rostral middle frontal (P < .001), paracentral (P < .001), and pars triangularis (P = .02) cortices. Thinning of the right caudal middle frontal and left entorhinal cortices was related to lower scores on a memory test administered closest to the second MRI visit (right caudal middle frontal cortex: standardized β = 0.

IMPORTANCE Results from longitudinal studies suggest that regular leisure time physical activity (LTPA) is associated with reduced risk of dementia or Alzheimer disease. Data on the association between LTPA and brain magnetic resonance imaging (MRI) measures remain scarce and inconsistent. OBJECTIVE To examine the association of LTPA and MRI-assessed brain aging measures in a multiethnic elderly population. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study included 1443 older (Ն65 years) adults without dementia who were participants of the Washington/Hamilton Heights-Inwood Columbia Aging Project study. LTPA, from self-reported questionnaire, was calculated as metabolic equivalent of energy expenditure. Both moderate to vigorous LTPA, assessed as meeting Physical Activity Guidelines for Americans (Ն150 minutes/week) or not, and light-intensity LTPA were also examined. EXPOSURES LTPA. MAIN OUTCOMES AND MEASURES Primary outcomes included total brain volume (TBV), cortical thickness, and white matter hyperintensity volume, all derived from MRI scans with established methods and adjusted for intracranial volume when necessary. We examined the association of LTPA with these imaging markers using regression models adjusted for demographic, clinical, and vascular risk factors. RESULTS The 1443 participants of the study had a mean (SD) age of 77.2 (6.4) years; 921 (63.8%) were women; 27.0%, 34.4%, and 36.3% were non-Hispanic White, non-Hispanic African American, and Hispanic individuals, respectively; and 27.3% carried the apolipoprotein E (APOE) ε4 allele. Compared with the LTPA of nonactive older adults, those with the most LTPA had larger (in cm 3) TBV

Introduction Numerous neuroimaging studies demonstrated an association between the apolipoprotein E (APOE) ε 4 allele and resting‐state functional connectivity (rsFC) of regions within the default mode network (DMN), both in healthy populations and patients with AD. It remains unclear whether the APOE ε 4 allele differentially affects the brain's functional network architecture across race/ethnicity. Methods We investigated rsFC within DMN subsystems in 170 APOE ε 4 carriers compared to 387 APOE ε 4 non‐carriers across three major racial/ethnic groups, including non‐Hispanic Whites (n = 166), non‐Hispanic Blacks (n = 185), and Hispanics (n = 206) from the Washington Heights‐Inwood Columbia Aging Project. Results Compared to APOE ε 4 non‐carriers, APOE ε 4 carriers had lower rsFC in temporal DMN, but only in non‐Hispanic Whites. Non‐Hispanic Black and Hispanic APOE ε 4 carriers had slightly higher or similar rsFC compared with non‐Hispanic White APOE ε 4 non‐carriers. Discussion These findings suggest that APOE ε 4 modulates DMN rsFC differently in non‐Hispanic Whites compared with non‐Hispanic Blacks and Hispanics.

Background Alzheimer’s disease and related disorders (ADRD) disproportionately affect African American, Hispanic, and American Indian older adults. Previous studies report racial/ethnic differences in markers of aging and neurodegeneration, but results are inconsistent due to small, non‐representative samples. We hypothesized that accelerated aging would manifest as a stronger negative relationship between age and MRI biomarkers among community‐dwelling racial/ethnic minorities compared with non‐Hispanic Whites. Method ADRD‐related neuroimaging measures of composite cortical thickness (CT) in AD signature regions and white matter hyperintensity (WMH) volume were assessed in White (n=274), Black (n=451), and Hispanic (n=663) participants from community‐based, intergenerational studies of cognitive aging and dementia. WHICAP participants are Medicare‐eligible participants aged 65 and older. The Offspring cohort includes middle‐aged children of the WHICAP study participants (of the 1482 participants, 1209 families were represented). We examined the association of cohort age and race/ethnicity with each imaging marker, after adjusting for sex/gender and family relatedness, and tested interactions between cohort age and race/ethnicity in separate models. Result WHICAP participants were 75±6.5 years old and Offspring participants were 55±10.5 years old at time of MRI. As expected, WHICAP participants had lower CT in AD signature regions than Offspring (β=‐.06,95%CI:‐.05,‐.08). Compared with Whites, Blacks and Hispanics had lower CT in AD signature regions, but an interaction between cohort age and race/ethnicity revealed that older Blacks had disproportionately thinner CT in AD signature regions (β=‐.05,95%CI:‐.01,‐.10). Offspring participants had lower WMH volume than WHICAP participants (β=‐1.4,95%CI:‐2.1,‐.58). Blacks had more WMH burden overall (β=1.04,95%CI:.13,2.0), but there were no interactions between race/ethnicity and cohort age on WMH burden. Conclusion Among diverse, community‐based participants, there are disparities in markers of brain atrophy in both cohorts but this effect is intensified with age, where older Blacks show disproportionately greater brain atrophy compared with other groups. Disparities in small vessel cerebrovascular disease are apparent in middle‐age and late‐life, but this effect is similar across age‐groups. Results suggest that racial/ethnic disparities in markers of brain aging and disease are apparent even in middle‐age and, in the case of neurodegeneration, may amplify with increasing age. These differences may be due to accelerated aging secondary to sociocultural factors and experiences.

Background The 2018 NIA‐AA Alzheimer’s disease (AD) research framework moves towards a multiple biomarker approach to explain AD development and progression more fully. This research framework has the flexibility to incorporate various biomarkers into a full or partial amyloid‐tau‐neurodegeneration (A/T/N) profile. The objective of this study was to determine the relative contribution of white matter hyperintensities (WMH) to amyloid and neurodegeneration on cognition in a diverse, community‐based cohort of older adults. Method A subset of cognitively healthy participants (n=155; age=69‐99yrs; 65% women, 30%/44%/26% Non‐Hispanic White/Non‐Hispanic Black/Hispanic) from the Washington Heights‐Inwood Columbia Aging Project underwent baseline Florbetaben PET (amyloid SUVR), T1‐weighted (cortical thickness[mm]) and T2‐weighted FLAIR MRI (WMH volume[cm3]), as well as subsequent neuropsychological assessments and consensus diagnoses every 1.5 years (up to 6 visits). Linear mixed effects models were used to test for change over time in language, memory, executive function, and visuospatial ability, while cox proportional hazard models were used to test for risk of developing MCI or AD. Biomarkers of interest included amyloid, cortical thickness, and WMH, adjusted for demographics (sex/gender, race/ethnicity, education). Interactions between biomarkers and time (e.g., slope differences) were evaluated as significant below 0.1. Result In A/N/V models, higher amyloid was associated with faster rates of decline in language (B [95%CI]: ‐0.08 [‐0.13, ‐0.02]), memory (‐0.13 [‐0.21, ‐0.05]), and visuospatial ability (‐0.05 [‐0.12, 0.01]), higher WMH was associated with faster rates of decline in executive function (‐0.05 [‐0.11, 0.009]) and visuospatial ability (‐0.02 [‐0.05, 0.005]), and lower cortical thickness was associated with lower executive function scores (1.6 [0.10, 3.0]). Individuals were more likely to develop MCI or AD with higher amyloid (Hazard Ratio=4.2, [1.1, 15.9]), but not with higher WMH (1.2 [0.83, 1.7]) or lower cortical thickness (0.03 [4E‐4, 2]). Conclusion In this imaging subsample of older community‐dwelling adults, cognitive decline is differentially associated by domain with amyloid or vascular burden, while broader, multi‐domain cognitive impairment necessary for MCI or AD diagnoses is associated with amyloid, one of the hallmark AD pathologies. Results support the use of complementary information from biomarker profiles, including traditional AD, vascular, and neurodegenerative biomarkers, to investigate AD and related dementias.