Basal Ganglia Perivascular Space Enlargement Is Associated with Sustained Amyloid-β Accumulation in the Alzheimer's Disease Continuum: A Longitudinal Study

The perivascular spaces (PVS) serve as primary conduits for brain waste clearance. PVS enlargement (EPVS) is commonly observed in aging and neurodegenerative conditions. However, it remains unclear whether EPVS influences the β-amyloid (Aβ) deposition in Alzheimer's disease (AD).

We included 524 participants from the ADNI database, all of whom had at least one follow-up ¹⁸F-florbetapir (FBP) PET scan. Using a deep-learning segmentation method, we calculated the PVS volume fraction (PVSVF) in the basal ganglia (BG) and white matter (WM) regions for each participant. Participants were then categorized into high- and low-EPVS-burden groups based on the median PVSVF. Linear mixed-effects models were employed to investigate the relationship between PVSVF and the annual rate of change in FBP PET standardized uptake value ratio (SUVR), incorporating both the linear and quadratic terms of baseline FBP SUVR. Analyses were performed for the entire cohort and within AD subgroups. For WM EPVS, additional analyses were conducted after excluding participants with severe white matter hyperintensity.

We confirmed that the annual rate of change in FBP SUVR follows an inverted U-shaped relationship with baseline FBP SUVR. Regarding BG EPVS, a significant interaction was identified between PVSVF and the squared baseline FBP SUVR in predicting the annual rate of change in FBP SUVR (FBP SUVR² × BG PVSVF: β = 8.350, P = 0.001). The high BG EPVS burden group showed sustained Aβ accumulation at the late disease period. In contrast, WM PVSVF showed no association with the annual rate of change in FBP SUVR. Similar results were observed within the AD continuum groups.

Higher baseline BG-EPVS burden was associated with a more sustained rate of amyloid-β accumulation among participants with high baseline amyloid burden.