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)-epsilon 4 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-epsilon 4 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-epsilon 4 status on cross-sectional naming performance (beta = -0.002, p = 0.002), and executive function excluding outliers (beta = 0.001, p = 0.009). There were no significant longitudinal interactions (p-values>0.10) except for Coding excluding outliers (beta = 0.002, p = 0.05). While cross-sectional models stratified by APOE-epsilon 4 status indicated greater ePVS related to worse cognition mostly in APOE-epsilon 4 carriers, longitudinal models stratified by APOE-epsilon 4 status showed greater ePVS volume related to worse cognition among APOE-epsilon 4 non-carriers only. Results indicated that greater ePVS volume interacts with APOE-epsilon 4 status on cognition cross-sectionally. Longitudinally, the association of greater ePVS volume and worse cognition appears stronger in APOE-epsilon 4 non-carriers, possibly due to the deleterious effects of APOE-epsilon 4 on cognition across the lifespan.