Associations of Vascular Risk Factors and APOE Genotype With Perivascular Spaces Among Community‐Dwelling Older Adults

BACKGROUND: Evidence suggests that enlarged perivascular spaces (PVSs) may represent a marker for cerebral small‐vessel disease. We investigated whether vascular risk factors are correlated with visible PVS in older adults. METHODS AND RESULTS: This population‐based study included 530 participants (age ≥60 years) who were free from dementia and functional dependence, derived from the Swedish National study on Aging and Care in Kungsholmen (2001–2003). We collected data on demographics, vascular risk factors, and health conditions through interviews, clinical examinations, laboratory tests, and patient registers. Cerebral PVSs and white matter hyperintensities on magnetic resonance images were visually assessed with semiquantitative visual rating scales. Data were analyzed using the general linear regression models. After controlling for demographics and cardiovascular disease, very high blood pressure (≥160/100 mm Hg) was significantly associated with global PVS score (β‐coefficient, 1.30; 95% CI, 0.06–2.53) and orthostatic hypotension was associated with PVS score in the basal ganglia (β‐coefficient 0.37; 0.03–0.70), but the associations became non‐significant when adjusting for white matter hyperintensity load. Orthostatic hypotension was significantly associated with global and lobar PVS scores in carriers but not in noncarriers of the APOE ε4 allele. Global or regional PVS score was not significantly associated with other traditional vascular risk factors such as smoking, diabetes mellitus, physical inactivity, and overweight or obesity. CONCLUSIONS: This study provides limited evidence supporting a correlation of magnetic resonance imaging–visible PVS with traditional vascular risk factors in older adults. The association of orthostatic hypotension with lobar PVS among APOE ε4 carriers suggests that lobar PVS may be a marker for amyloid‐associated small‐vessel disease.