Perivascular space enlargement accelerates with hypertension, white matter hyperintensities, chronic inflammation, and Alzheimer’s disease pathology: evidence from a three-year longitudinal multicentre study

Abstract

BackgroundPerivascular space (PVS) enlargement in ageing and Alzheimer’s disease (AD) and its exacerbators require further investigation.MethodsWe studied centrum semiovale (CSO) and basal ganglia (BG) PVS computationally over three to four annual visits in 557 participants of the DZNE multicentre DELCODE cohort. We tested volumetric changes of PVS in relation to ageing, sex, years of education, hypertension, AD diagnosis, and cerebrospinal-fluid-derived Amyloid and Tau positivity and interleukin 6 (IL-6).ResultsPVS volumes increased over time. PVS enlargement was associated with baseline white matter hyperintensities. BG-PVS enlargement was related to age and was faster with hypertension. CSO-PVS volumes increased faster with Amyloid and Tau positivity. Higher CSF IL-6 levels predicted PVS volume expansion in both regions and were associated with accelerated PVS enlargement in individuals with Amyloid and Tau positivity.ConclusionOur work supports the region-specific involvement of white matter hyperintensities, neurotoxic waste accumulation, and inflammation in PVS enlargement.