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Enlarged Spaces in the Brain Predict Dementia Risk

Sue Hughes
February 02, 2021

Peivascular spaces are fluid-filled spaces that surround small blood vessels within the brain parenchyma. Individuals whose perivascular spaces are enlarged may be more likely to develop cognitive decline and dementia in the next few years, a new study suggests.

"These enlarged perivascular spaces seem to be an independent marker of cerebrovascular disease and are something else we can be looking out for on MRI scans when judging risk of cognitive decline and when trying to make a diagnosis," lead author Matthew Paradise, MBChB, University of New South Wales, Sydney, Australia, told Medscape Medical News.

"Our findings emphasize again the strong association between cerebrovascular disease and cognitive impairment and dementia. This gives more weight to the argument that addressing vascular risk factors earlier in life will help ward off cognitive decline and dementia in later life," he added.

The study was published online in Neurology on January 27.

The authors note that there is increasing evidence of the association of MRI-visible dilated perivascular spaces with small-vessel disease and neurodegenerative pathology, but few longitudinal studies have examined their association with incident dementia.

They conducted the current study to investigate whether enlarged perivascular spaces in two areas of the brain where they are commonly seen -- the basal ganglia and the centrum semiovale -- are associated with decline in cognition and incident dementia.

They point out that enlarged perivascular spaces in these two regions may represent partially different pathophysiology. Those in the basal ganglia are associated with more hypertension-related pathology, and those in the centrum semiovale are associated with amyloid pathology and therefore possibly Alzheimer's.

"These regions may in turn be associated with impairments in different cognitive domains, resulting from damage to specific cognitive networks and/or due to underlying pathology," the authors suggest.

The study involved 414 community-dwelling individuals (average age, 80 years) who underwent cognitive tests at baseline and every 2 years for 8 years. Participants also underwent MRI brain scans at baseline, and the numbers of perivascular spaces in two representative slices in the basal ganglia and centrum semiovale were counted. Severe perivascular space pathology was defined as those in the top quartile.

Results showed that participants with severe perivascular space pathology in both regions or in the centrum semiovale alone experienced greater decline in global cognition over 4 years, after adjustment for the presence of other neuroimaging markers of small-vessel disease.

The presence of severe perivascular space pathology in both regions was an independent predictor of dementia over 8 years (odds ratio, 2.91; P = .003).

Further, the presence of severe perivascular space pathology in all groups examined was associated with greater dementia risk at either year 4 or year 6.

A total of 97 individuals (24%) were diagnosed with dementia during the study. Of the 31 people with severe cases of perivascular space enlargement in both areas of the brain, 12 (39%) were diagnosed with dementia.

"Our study shows that these enlarged perivascular spaces aren't just incidental findings. These results suggest that there is an independent mechanism for the perivascular spaces as a biomarker of cognitive impairment and dementia apart from being a general marker of disease in the small vessels," Paradise said. "For example, enlarged perivascular spaces may be a biomarker of impaired waste clearance in the brain."

Paradise said it is believed these perivascular spaces are more linked to cerebrovascular disease than to Alzheimer's and that their presence will help in assessing and quantifying cerebrovascular disease.

"We're not very good at assessing cerebrovascular disease. It's a difficult judgment to make -- what type of dementia a patient has," he explained. "We look at brain atrophy in particular areas, and white matter hyperintensities and damage to microscopic blood vessels; these are all linked to an increased risk of cognitive impairment. Perivascular spaces are one more measure that can help.

"More research is needed to understand how these enlarged spaces develop, as they could be an important potential biomarker to help with early diagnosis of dementia, prognosis, and subtyping," Paradise concluded. The authors note that future studies should distinguish analyses of perivascular spaces by region and attempt to standardize visual rating.

The study was supported by the Australian National Health and Medical Research Council and the Josh Woolfson Memorial Scholarship. The authors report no relevant financial relationships.

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Reviewed on 2/3/2021
References
SOURCE: Medscape, February 02, 2021. Neurology. Published online January 27, 2021.

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