Perivascular space burden interacts with APOE-ε4 status on cognition in older adults.

Enlarged perivascular spaces (ePVS) may adversely affect cognition. Little is known about how basal ganglia ePVS interact with apolipoprotein (APOE)-ε4 status. Vanderbilt Memory and Aging Project participants (n = 326, 73 ± 7, 59% male) underwent 3 T brain MRI at baseline to assess ePVS and longitudinal neuropsychological assessments. The interaction between ePVS volume and APOE-ε4 carrier status was related to baseline outcomes using ordinary least squares regressions and longitudinal cognition using linear mixed-effects regressions. ePVS volume interacted with APOE-ε4 status on cross-sectional naming performance (ß = -0.002, p = 0.002), and executive function excluding outliers (ß = 0.001, p = 0.009). There were no significant longitudinal interactions (p-values>0.10) except for Coding excluding outliers (ß = 0.002, p = 0.05). While cross-sectional models stratified by APOE-ε4 status indicated greater ePVS related to worse cognition mostly in APOE-ε4 carriers, longitudinal models stratified by APOE-ε4 status showed greater ePVS volume related to worse cognition among APOE-ε4 non-carriers only. Results indicated that greater ePVS volume interacts with APOE-ε4 status on cognition cross-sectionally. Longitudinally, the association of greater ePVS volume and worse cognition appears stronger in APOE-ε4 non-carriers, possibly due to the deleterious effects of APOE-ε4 on cognition across the lifespan.

Baseline grey matter volumes and white matter hyperintensities predict decline in functional activities in older adults over a 5-year follow-up period.

INTRODUCTION: Functional independence is an essential predictor of quality of life in aging, yet few accessible predictors of functional decline have been identified. This study examined associations between baseline structural neuroimaging markers and longitudinal functional status. METHODS: Linear mixed effects models with follow-up time interaction terms related baseline grey matter volume and white matter hyperintensities (WMHs) to functional trajectory, adjusting for demographic and medical covariates. Subsequent models assessed interactions with cognitive status and apolipoprotein E (APOE) ε4 status. RESULTS: Smaller baseline grey matter volumes, particularly in regions commonly affected by Alzheimer's disease (AD), and greater baseline WMHs were associated with faster functional decline over a mean 5-year follow-up. Effects were stronger in APOE-ε4 carriers on grey matter variables. Cognitive status interacted with most MRI variables. DISCUSSION: Greater atrophy in AD-related regions and higher WMH burden at study entry were associated with faster functional decline, particularly among participants at increased risk of AD.