Pathology of perivascular spaces correlates with cognitive decline, dementia

Severe perivascular space pathology served as a marker of increased risk for cognitive decline and dementia regardless of other markers of small vessel disease, according to findings from a prospective cohort study published in Neurology.

“There is increasing evidence for the association of MRI-visible dilated [perivascular spaces] with small vessel disease and neurodegenerative pathology,” the researchers wrote. “Few longitudinal studies have examined the association of [perivascular spaces] with incident dementia.”

Matthew Paradise, MBChB, MSc, a research fellow at the Center for Healthy Brain Aging at the University of New South Wales, and colleagues examined data from a retrospective cohort study to ascertain whether severe perivascular space (PVS) dilation correlated with longitudinal cognitive decline and incident dementia. They also analyzed the examined impact of PVS severity in the basal ganglia (BG) and the centrum semiovale (CSO), regions in which PVS are common, on impairments in specific cognitive domains.

The researchers examined 414 community-dwelling adults aged 72 to 92 years at baseline and biennially for up to 8 years using cognitive assessments, consensus dementia diagnoses and 3T MRI. They calculated the numbers of PVS in “two representative slices” in the BG and the CSO, defining severe PVS pathology as the top quartile. They also determined “the effects of severe PVS pathology in i) either region; ii) both regions; and those with iii) severe BG PVS and iv) severe CSO PVS.”

Mean age of patients was 79.8 years. Fewer than half (47%) were men.

The researchers observed severe PVS pathology in either region among 38% of participants, severe pathology in both regions among 7% of individuals, severe BG PVS pathology in 22% and severe CSO PVS pathology in 24%.

Participants with severe PVS pathology in the CSO only or both regions experienced greater decline in global cognition over 4 years, even after the researchers adjusted for markers of other small-vessel diseases on neuroimaging. The presence of severe PVS pathology in both the BG and CSO served as an independent predictor of dementia over 8 years (OR = 2.91; 95% CI, 1.43-5.95). The researchers also observed that the presence of severe PVS pathology in all groups correlated with increased risk for dementia at either 4 years or 6 years.

A dementia analysis of 400 study participants that excluded 10 diagnosed with dementia at baseline and four with missing dementia information found that 24% were diagnosed with dementia in 8 years of follow-up. Among those with severe PVS in either region, 26% developed dementia. In participants with severe PVS in both regions, 39% developed dementia, while 30% participants with severe BG PVS and 27% with severe CSO PVS at baseline developed dementia.

The correlations between PVS region pathology and cognitive decline, as well as incident dementia, indicated “differences in their underlying pathology and/or differential impacts due to the location of PVS and effect on white matter tracts,” according to Paradise and colleagues.

“Further research is needed into the etiology and sequelae of PVS pathology since PVS may be an important potential biomarker to help with early dementia diagnosis, prognosis and subtyping,” the researchers wrote. “Importantly, future studies should divide PVS analyses by region and attempt to standardize PVS visual rating. Study duration needs to be carefully considered when examining incident dementia due to the interaction of time with PVS.”