Dementia Tied to Large Perivascular Spaces

Enlarged fluid-filled spaces around cerebral small blood vessels were linked to cognitive decline, a prospective study of older adults showed.

Severe perivascular space pathology in both the basal ganglia and the centrum semiovale, or in the centrum semiovale alone, was tied to a greater drop in global cognition over 4 years, reported Matthew Paradise, MBChB, MSc, of the University of New South Wales in Sydney, Australia, and co-authors.

Large perivascular space dilation in both brain regions was an independent predictor of dementia across 8 years of follow-up (adjusted OR 2.91, 95% CI 1.43-5.95, P=0.003), with stronger effects at either year 4 or 6, the researchers wrote in Neurology.

Dilated perivascular spaces are a common MRI finding especially in older patients, but their clinical relevance is unclear, Paradise noted. “Our study suggests that dilated perivascular spaces should no longer be considered just an incidental finding but have an important role in evaluating cognitive decline,” he told MedPage Today.

“Cerebrovascular disease is increasingly recognized not only as an important cause of cognitive impairment and dementia directly, but also as an important contributor to the risk and progression of Alzheimer’s disease,” Paradise added. “Despite this, we’re not very good at assessing the overall burden from cerebrovascular disease which can make diagnosis of, say, vascular dementia, difficult.”

As people get older, and in some diseases, perivascular spaces around cerebral small vessels can enlarge, noted David Werring, PhD, of UCL Queen Square Institute of Neurology in London, England, who wasn’t involved with the study. “This raises the possibility that perivascular spaces could be a marker of disease process affecting these small vessels,” he said.

The location of enlarged perivascular spaces may reflect the type of underlying small vessel pathology, Werring pointed out. “Brain imaging studies have found associations between enlarged basal ganglia perivascular spaces and deep hemorrhages in the brain, while enlarged centrum semiovale perivascular spaces are linked to superficial hemorrhages and markers of cerebral amyloid angiopathy,” he told MedPage Today.

“This, together with other lines of evidence, suggests that basal ganglia perivascular spaces relate to abnormal deep small vessels affected by deep perforator arteriopathy, while centrum semiovale perivascular spaces are associated with the accumulation of amyloid-beta pathology, including its deposition in superficial small vessels as cerebral amyloid angiopathy,” he said.

In their analysis, Paradise and colleagues looked at 414 people ages 72 to 92 in the Sydney Memory and Aging Study who were assessed at baseline and biennially for up to 8 years with cognitive assessments, dementia diagnoses, and 3T MRI. The researchers counted the number of perivascular spaces in two representative slices in the basal ganglia and centrum semiovale, defining severe pathology as the top quartile. They also calculated white matter hyperintensity volume, cerebral microbleed number, and lacune number.

Participants had a mean age of 79.8 and 47% were men. Overall, 38% had severe perivascular space pathology in either region: 7% had severe pathology in both areas, 22% had severe pathology in the basal ganglia, and 24% in the centrum semiovale. Groups did not vary by age, sex, or vascular risk factors.

People with severe basal ganglia perivascular space pathology had greater white matter hyperintensity volume (P=0.004) and were more likely to have lacunes (17% vs 6%, P=0.002) and multiple cerebral microbleeds (23% vs 9%, P=0.002) than people with absent or mild basal ganglia pathology. In contrast, people with severe centrum semiovale perivascular space dilation did not have greater amounts of other small vessel disease pathology.

Participants with severe pathology in both locations had more rapid decline in global cognition than those with less perivascular space enlargement. This remained significant after adjusting for demographics, vascular risk factors, and other neuroimaging measures (unstandardized B -0.175 ± 0.076, P=0.02). Severe basal ganglia perivascular space dilation by itself was not associated with global cognitive decline, but severe pathology in the centrum semiovale alone was (B -0.111 ± 0.048, P=0.02).

Over 8 years of follow-up, 24% of participants were diagnosed with dementia. Among people with severe perivascular space pathology in either region, 26% developed dementia; of those with severe pathology in both regions, 39% developed dementia. The strongest effect occurred at year 4 in people with severe pathology in both areas (OR 4.75, 95% CI 1.51-14.95, P=0.008).

“The effect was nuanced and we did not see an impact of increased dementia rates at 8 years,” Paradise said. “By this stage, a much larger proportion of participants in our study developed dementia and the signal from dilated perivascular spaces may have been overpowered by the effect from age.”

The study had several limitations. While 8-year follow-up is fairly extensive, longer periods may be more informative for dementia analysis. The researchers had detailed cognitive data for only 4 years. The two predetermined slices may have missed perivascular spaces in other areas, especially in people with atypical distribution patterns.