The Next Target to Fight Dementia: White Matter Disease

Brain scientists have found that white matter disease chips away at memory by shrinking the brain, and contributing to dementia more than initially thought.

“These findings highlight that the role of white matter disease in dementia has been under-appreciated,” says  Walter Swardfager, lead investigator of a new study and an assistant professor in the Department of Pharmacology and Toxicology. . “This may help to direct the next generation of treatment strategies.”

White matter hyperintensities (WMH) are bright spots on MRI scans – tissue in the brain that is wearing away due to effects of aging and vascular risk factors on the brain’s small vessels.

The research, published in the February 2018 issue of the journal Neurology, showed that individuals with extensive small vessel disease had profound shrinking of the temporal lobe, an important brain region that is instrumental to learning and memory function.

The study included over 700 participants of the Sunnybrook Dementia Study led by. Sandra E. Black, the Brill Chair in Neurology in the Deparmtent of Medicine.  The researchers’ analyses showed that shrinkage of the temporal lobe explained how WMH were associated with memory problems.

WMH was associated with poorer verbal recall, specifically due to temporal lobe shrinkage and poorer verbal learning. WMH also contributed to deficits in recognition memory – the most sensitive and specific cognitive sign of Alzheimer’s disease - in people with Alzheimer’s disease, and across other late-life dementia syndromes including post-stroke dementia.

Large vessel strokes increase the risk of dementia substantially, and similarly, small vessel disease is very often a “silent” contributor to cognitive decline and dementia. Since they contribute to brain shrinkage and memory problems, it is important to consider vascular brain disease as a “root cause” that can set the stage for dementia, stress the researchers.

“More work needs to be done to show how white matter imaging markers can be used to predict cognitive decline in Alzheimer’s disease as well as stroke,” says Swardfager, also a scientist at Sunnybrook Research Institute. “It is now important for research to focus on the biological bases for white matter disease, and how it affects brain tissue at the molecular level, so that new treatments can be designed to protect the brain from damage.”

The study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Alzheimer Society of Canada, Heart and Stroke Foundation of Canada, the Physicians Services Incorporated Foundation, Alzheimer’s Association Research Grant Program and Brain Canada.

The research team is a collaboration of scientists from Sunnybrook Research Institute, University of Toronto, University Health Network Toronto Rehabilitation Institute, Universidade Federal De São Paulo, McMaster University, and Rotman Research Institute at Baycrest.