Arenaza‐Urquijo, Eider M

Abstract Background Neighborhood socio‐economic conditions may increase Alzheimer's disease (AD) risk through amyloid, tau, atrophy or vascular pathways, potentially varying by genetic risk, race or ethnicity and sex. We examined associations between Area Deprivation Index (ADI) and cognition, AD pathology, gray matter (GM) and white matter hyperintensities (WMH) volume in cognitively unimpaired older adults by race or ethnicity, sex and APOE4 status. Method We included 1896 non‐demented older adults from US POINTER study with available cognitive evaluations, ADI level – a census–based neighborhood disadvantage metric (categorized as low, moderate and high) and a subsample with neuroimaging data ( N = 806). Linear/logistic regressions were used to assess interactions of ADI with sex, race or ethnicity, and APOE4 on (1) the Preclinical Alzheimer's Cognitive Composite, (PACC‐5), (2) MRI‐derived GM volume meta‐ROI (entorhinal, fusiform, parahippocampal, mid‐temporal, inferior temporal), (3) WMH and (4) AD pathology (amyloid and tau PET), adjusted by age, sex and intracranial volume when appropriate. Result African American participants ( p <0.001) and females ( p <0.001) were more likely to live in deprived areas. African American participants had significantly lower PACC‐5 ( p <0.001) and GM volume ( p <0.001), “Other or multiple races” participants showed significantly higher amyloid burden ( p = 0.001), and White participants higher WMH ( p = 0.013). Females showed higher PACC‐5 scores ( p <0.001), while APOE4 carriers showed lower PACC‐5 ( p = 0.042) and higher amyloid burden ( p <0.001) (Table 1). Race and ADI interacted on PACC‐5 ( p = 0.043) and showed a borderline interaction on Tau ( p = 0.079), with higher ADI linked to lower PACC‐5 in White, Hispanic, and “Other or Multiple Races” and higher Tau in Hispanic. Further, there was a borderline ADI*APOE4 status interaction on WMH ( p = 0.059) and a significant ADI*APOE4 interaction on amyloid ( p = 0.001), where APOE4 carriers in deprived areas showed higher WMH and lower amyloid burden (Figure 1). No significant ADI*sex interactions were observed. Conclusion Neighborhood disadvantage was more commonly observed in African American participants, but interaction with cognition was primarily seen in other racial/ethnic groups. APOE4 carriers showed increased amyloid burden, but those from more disadvantaged neighborhoods exhibited a higher vascular component alongside lower amyloid‐driven pathology. These results may indicate varying effects of social disadvantages across groups or sample bias.

Abstract Background Neighborhood social and built environment characteristics may promote physical activity, a modifiable factor for dementia risk, which may in turn promote cognitive and brain health. We explored the associations of the U.S. National Walkability Index ‐ a nationwide geographic data resource that ranks block groups according to their relative walkability – with cognitive function, gray matter (GM) and white matter hyperintensities (WMH), neighborhood disadvantage, sedentary behavior and frequency of physical activity in cognitively unimpaired older adults at increased Alzheimer's disease (AD) risk. Method We included baseline data from 1398 older adults (68.3 ± 5.17 years, 68.3% females, 30.5% APOE4 carriers) from the U.S. POINTER trial. Walkability was classified as: least, below average, above average and most walkable. Neighborhood disadvantage (low, moderate and high) was assessed using Area Deprivation Index (ADI) ( N = 1384). Physical inactivity was assessed using the Sedentary Behavior Questionnaire (SBQ, hours sitting/week, N = 1106), and physical activity was measured with a composite score from the Community Health Activities Model Program for Seniors (CHAMPS) questionnaire. Linear and logistic regressions examined associations between walkability and (1) physical activity and sedentary behavior; and (2) cognition assessed with the Preclinical Alzheimer's Cognitive Composite (PACC‐5), GM volume and WMHs, Additionally, associations between neighborhood disadvantage and physical activity and sedentary behavior were explored. Models were adjusted for age, sex, race, APOE4 and total intracranial volume. Result More deprived areas were generally less walkable (β = ‐0.008, p < 0.001) (Figure 1). Higher walkability (Above average: β = 0.192, p = 0.011 and most walkable: β = 0.183, p = 0.032) was associated with higher PACC‐5 (Figure 2A) scores but not with more preserved GM or lower WMH. Walkability scores were not associated with physical activity and sedentary measurements, while greater neighborhood disadvantage was linked to sedentary behavior (β = 0.126, p < 0.001) (Figure 2B). Conclusion These results suggest that physical inactivity in more deprived areas is associated with neighborhood socioeconomic disadvantages rather than built environment. Additionally, walkability scores were not associated with any measure of physical activity or brain health, suggesting the need to further investigate other health effects of neighborhood disadvantage and walkability.