By Samantha Sexton
New research from scientists at Sunnybrook Research Institute has found more evidence that cognitive deficits in dementia may be partly explained by a direct link between vascular disease and brain shrinkage.
The findings were published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“Despite the frequent co-existence of Alzheimer’s disease (AD) with small vessel disease (SVD), AD has traditionally been viewed as a disease of the brain cells, where misfolded amyloid-beta proteins accumulate into plaques. However, there is growing evidence that AD is also a disease of the brain vessels,” says Dr. Julie Ottoy, a postdoctoral researcher at Sunnybrook Research Institute and first author of the study. “The AD research community is recognizing the urgent need to stop focusing on AD as a ‘pure’ nerve cell degeneration and to start to better understand mixed cohorts exhibiting both AD- and SVD-related pathologies.”
As part of a collaborative effort across seven Canadian sites, the study team recruited a unique cohort of patients with mild cognitive impairment and early AD from memory and stroke-prevention clinics. The participants were required to have moderate to severe small vessel disease, evident as confluent patches on MRI in the brain’s white matter, referred to as “white matter hyperintensities”. These were compared to similar cases drawn from the Alzheimer Disease Neuroimaging Initiative, who had lower amounts of white matter hyperintensities.
Patients received an MRI scan, a glucose metabolic PET scan, an amyloid PET scan, and brief neuropsychological testing as part of the study. The researchers observed that increased total white matter hyperintensity volume (quantified via their artificial intelligence-based models) was associated with poorer performance in cognitive testing. Through advanced statistical analyses they found that this association was mainly orchestrated by shrinkage of brain regions typically associated with AD.
“These results suggest, based on neuroimaging techniques, that cognitive deficits in AD may be partly explained by a direct link between vessel and neurons, whereby progressive damage to the vessel wall may accelerate brain tissue (gray matter) shrinkage,” says Dr. Maged Goubran, scientist in the Physical Sciences Platform and the Hurvitz Brain Sciences Program at Sunnybrook and senior author of the study.
However, the researchers explain the study also elucidated a role for amyloid, one of the abnormal proteins in the brain associated with AD. Amyloid deposits may partly orchestrate the link between vascular and neuronal damage.
“One potential mechanism may be that thickened vessel walls – influenced by genetic and vascular risk factors – lead to reduced blood vessel perfusion, thereby impairing the clearance of toxic amyloid and thus promoting its accumulation,” explains Dr. Sandra Black, co-senior author of the study and scientific director of the Dr. Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook.
To date, there is no cure for AD and many clinical trials have failed to show clear cognitive benefit.
“Our study supports the idea that patients with SVD may represent an at-risk group for neurodegeneration and potential accumulation of harmful protein aggregates,” says Dr. Maged Goubran. “A key therapeutic or preventive approach may be to slow down the effects of SVD from mid-life, potentially limiting additional neuronal loss and exacerbation of AD pathology later in life. Our research is an important step forward towards better understanding the complex role of SVD in dementia.”
Samantha Sexton is a communications advisor at Sunnybrook Health Sciences Centre.
