Identifying risk factors for brain atrophy during the aging process can help direct new preventive approaches for dementia and cognitive decline. The association of neighborhood socioeconomic disadvantage with brain volume in this context is not well known.OBJECTIVE To test whether neighborhood-level socioeconomic disadvantage is associated with decreased brain volume in a cognitively unimpaired population enriched for Alzheimer disease risk. DESIGN, SETTING, AND PARTICIPANTSThis study, conducted from January 6, 2010, to January 17, 2019, at an academic research neuroimaging center, used cross-sectional data on 951 participants from 2 large, ongoing cohort studies of Alzheimer disease (Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center clinical cohort). Participants were cognitively unimpaired based on National Institute on Aging-Alzheimer's Association workgroup diagnostic criteria for mild cognitive impairment and Alzheimer disease, confirmed through a consensus diagnosis panel. The cohort was enriched for Alzheimer disease risk based on family history of dementia. Statistical analysis was performed from April 3 to September 27, 2019. MAIN OUTCOMES AND MEASURESThe Area Deprivation Index, a geospatially determined index of neighborhood-level disadvantage, and cardiovascular disease risk indices were calculated for each participant. Linear regression models were fitted to test associations between relative neighborhood-level disadvantage (highest 20% based on state of residence) and hippocampal and total brain tissue volume, as assessed by magnetic resonance imaging. RESULTSIn the primary analysis of 951 participants (637 women [67.0%]; mean [SD] age, 63.9 [8.1] years), living in the 20% most disadvantaged neighborhoods was associated with 4.1% lower hippocampal volume (β = −317.44; 95% CI, −543.32 to −91.56; P = .006) and 2.0% lower total brain tissue volume (β = −20 959.67; 95% CI, −37 611.92 to −4307.43; P = .01), after controlling for intracranial volume, individual-level educational attainment, age, and sex. Robust propensity score-matched analyses determined that this association was not due to racial/ethnic or demographic characteristics. Cardiovascular risk score, examined in a subsample of 893 participants, mediated this association for total brain tissue but not for hippocampal volume.CONCLUSIONS AND RELEVANCE For cognitively unimpaired individuals, living in the most disadvantaged neighborhoods was associated with significantly lower cerebral volumes, after controlling for maximal premorbid (total intracranial) volume. This finding suggests an association of community socioeconomic context, distinct from individual-level socioeconomic status, with brain volume during aging. Cardiovascular risk mediated this association for total brain tissue volume but not for hippocampal volume, suggesting that neighborhood-level disadvantage may be associated with these 2 outcomes via distinct biological pathways.

Introduction: We examined the influence of enrollment factors demonstrated to differ by race on incident mild cognitive impairment and dementia using Alzheimer's Disease Center data. Methods: Differences in rates of incident impairment between non-Latino Whites and Blacks (n 5 12,242) were examined with age-at-progression survival models. Models included race, sex, education, source of recruitment, health factors, and family history of dementia. Results: No significant race differences in progression were observed in cognitively unimpaired participants. In those with mild cognitive impairment at baseline, Whites evidenced greater risk for progression than Blacks. Enrollment factors, for example, referral source, were significantly related to progression. Discussion: The finding that Blacks demonstrated lower rate of progression than Whites is contrary to the extant literature. Nested-regression analyses suggested that selection-related factors, differing by race, may account for these findings and influence our ability to accurately estimate risk for progression. It is potentially problematic to make racial comparisons using Alzheimer's Disease Center data sets. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

These analyses provide preliminary support for IICV as a marker of incident AD and MCI. This easily-disseminated, non-invasive marker compared favorably to well-established CSF biomarkers.

IntroductionThe potential of intra-individual cognitive variability (IICV) to predict incident mild cognitive impairment (MCI) or Alzheimer's disease (AD) was examined and compared to well-established neuroimaging and genetic predictors.MethodsIICV was estimated using four neuropsychological measures for n = 1324 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were cognitively healthy or diagnosed with MCI at baseline. IICV was used to predict time to incident MCI or AD, and compared to hippocampal volume loss and APOE ε4 status via survival analysis.ResultsIn survival analyses, controlling for age, education, baseline diagonosis, and APOE ε4 status, likelihood ratio tests indicate that IICV is associated with time to cognitive status change in the full sample (P < .0001), and when the sample was restricted to individuals with MCI at baseline (P < .0001).DiscussionThese findings suggest IICV may be a low-cost, noninvasive alternative to traditional AD biomarkers.

Background: It is well-documented that African Americans have elevated risk for cognitive impairment and dementia in late life, but reasons for the racial disparities remain unknown. Stress processes have been linked to premature age-related morbidity, including Alzheimer's and related dementias (ADRD), and plausibly contribute to social disparities in cognitive aging. Objective: We examined the relationship between stressful life events and cognitive decline among African American and White participants enrolled in the Wisconsin Registry for Alzheimer's Prevention (WRAP). Methods: Linear mixed models including demographic, literacy, and health-related covariates were used to estimate (1) relationships between a life event index score and decline in cognitive test performance in two domains of executive function (Speed & Flexibility, Working Memory) and one domain of episodic memory (Verbal Learning & Memory) among 1,241 WRAP enrollees, stratified by race, and (2) contributions of stressful life events to racial differences in cognition within the full sample.