Intracranial Atherosclerosis Not Linked to Amyloid

January 09, 2020

A new study shows no association between intracranial atherosclerotic plaque and brain beta-amyloid deposition in a community-based cohort of older adults without dementia.

"We know vascular risk factors are associated with later dementia, but our current results suggest that the mechanism by which vascular risk might act on dementia risk is probably not, at least entirely, through intracranial atherosclerosis," lead study author Rebecca Gottesman, MD, PhD, Johns Hopkins Hospital, Baltimore, Maryland, told Medscape Medical News.

The study was published online December 20 in JAMA Neurology.

"There has been some evidence that vascular risk factors are associated with elevated brain amyloid, and in particular, in some autopsy studies that cholesterol buildup in the arteries in the brain was associated with Alzheimer's-type changes," Gottesman explained.

"We wanted to study the relationship between atherosclerosis in the arteries of the brain in living individuals without dementia to see if it was associated with these Alzheimer's-type changes because this might identify an important potentially modifiable risk factor for Alzheimer's brain changes," she said.

For the study, researchers analyzed data from a subset of 300 individuals aged 70-90 years (mean age 76 years) without dementia from the Atherosclerosis Risk in Communities (ARIC) cohort study who underwent PET scanning to detect amyloid buildup. The same individuals also underwent brain MRI to evaluate intracranial atherosclerosis. 

Results showed no evidence of an association between plaque presence and global cerebral beta-amyloid. Furthermore, modest stenosis of the intracranial vessels was not associated with amyloid levels.

"We had hypothesized that we might find evidence of an association between intracranial atherosclerosis and brain amyloid based on earlier studies," Gottesman said. "However, this was a cross-sectional analysis — these sets of scans were basically done during the same time period for all study participants — which means we may have failed to find an association because the relationship may take years to occur. It is also possible, however, that vascular risk factors themselves act on risk for dementia and Alzheimer's," she added.  

Gottesman points out that intracranial atherosclerosis is known to be associated with dementia risk more broadly, emphasizing that more needs to be done to understand how this elevated risk occurs.  

"We need to understand more about the longer-term effect of intracranial atherosclerosis and how it impacts dementia and Alzheimer's risk over years to decades. Also, it is important to understand if certain subgroups of people might be especially susceptible to adverse effects of having intracranial atherosclerosis and how stroke fits in with these relationships," she commented.

Gottesman says the current results should not be taken as evidence that vascular dementia and Alzheimer's have completely different causes.

"Intracranial atherosclerosis is just one type of vascular effect in the brain, and other studies demonstrate that midlife vascular risk factors are more strongly associated with later-life cognition and even later-life brain amyloid, so we may just need to consider longer-term relationships between the two," she explained.

It could also be just one additional consequence of vascular risk factors that might act on the brain and on Alzheimer's risk in different ways, she added.

Furthermore, this study did not address how the relative amounts of intracranial atherosclerosis and brain amyloid each contribute to dementia risk, and thus, did not address how these affect clinically relevant dementia, Gottesman noted.

"We know there is a lot of overlap in the pathology of people with dementia, and other studies suggest that this applies to intracranial atherosclerosis and Alzheimer's changes in the brain in addition to other types of vascular changes that can be observed," she said.

The researchers suggest that potential mechanisms for an association between intracranial atherosclerosis and beta-amyloid may depend on a greater degree of stenosis than what was found in this generally healthy cohort or with a more cognitively impaired population at later stages in disease.

The ARIC study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), and US Department of Health and Human Services. Gottesman has reported receiving grants from the NIH/National Institute on Aging.

JAMA Neurol. Published online December 20, 2019. Abstract

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