White matter disease was originally considered a normal event in an aging brain. But Dr. Daniel Mandell and his research team have discovered that it might actually be caused by tiny strokes and contribute to vascular dementia. (Video: UHN)​
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Dementia is a term for declining mental abilities, such as memory difficulties, language problems and psychological impairment, which reduce a person's ability to perform everyday activities. There are several different brain diseases that cause dementia; however, they do have two things in common: the causes of these diseases are poorly understood and there are few good treatments for them.

But researchers at the Krembil Neuroscience Centre have discovered a possible cause of a common dementia, a finding that opens avenues for treatment. The source? White matter disease (leukoaraiosis).

This is your brain on aging

The human brain has a wafer-thin layer of folded grey matter on the surface, and white matter on the inside. The white matter consists of more than 100,000 kilometres of nerve fibres which connect parts of the grey matter with each other, and with the spinal cord and the rest of the body.​

Since Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) scanning emerged in the 1980s, doctors have noticed that as we age, the white matter of the brain commonly degenerates (and becomes spongy in appearance). By age 60, this degeneration, termed white matter disease, is present in more than half of the population.

Originally, white matter disease was considered a normal, age-related change. But over the last decade, medical experts have come to understand that the presence of large areas of disease in the white matter of the brain are associated with cognitive decline and dementia in patients.

Symptomless strokes

This prompted Dr. Daniel Mandell, a neuroradiologist with the Joint Department of Medical Imaging (JDMI), and his research team to find out what causes disease in the brain's white matter as we age. Since the disease increases over time, the researchers thought that the culprit might be repeated tiny, undiagnosed strokes – a stroke is when a lack of blood flow injures a part of the brain.

Dr. Mandell and his team hypothesized that each tiny stroke might be small enough to cause only a minor loss of brain function. Neither the patient nor his or her doctor would notice the problem until enough tiny strokes had accumulated over many years, causing enough damage for the patient to develop dementia.

To test this theory, the team recruited five adults between the ages of 57 and 79 who had moderate-to-severe disease in the white matter of the brain and no evidence of previous strokes. Each week, for 16 weeks, they took MRI scans of their brains.

As they had guessed, but still found surprising, the researchers observed new, tiny strokes appearing in the white matter over the course of the study (watch the above video to see the white matter disease progress over a few weeks). These strokes had no apparent symptoms as the study participants didn't experience any weakness, visual disturbance, or speech or language difficulties – all signs of a stroke.

"We were surprised to find strokes occurring in the majority of our study participants," said Dr. Mandell who is the principal investigator of the study. "But even more interesting, we noticed that over the course of the study, the damage from these tiny strokes became indistinguishable from the participants' existing white matter disease."

"If the study participants had only had two MRIs, once at the beginning of the study and again 16 weeks later, it would have been impossible to tell that their worsening white matter disease was caused by strokes," he added.

Possible treatment

Dr. Mandell's study is the first to provide compelling evidence that tiny silent strokes are a cause of age-related degeneration in the white matter of the brain potentially causing a type of dementia that can be prevented or stopped.

Unlike most degenerative types of dementia where there are very limited treatments, this type, based on vascular disease, is potentially more treatable. More research is needed to confirm these findings, but the detection of white matter disease could eventually become a trigger to treat patients aggressively for stroke risk factors such as high cholesterol, lack of exercise, high blood pressure etc. to prevent further cognitive decline.

Published October 30 in the journal Annals of Neurology, this research is a major leap forward in our understanding of the aging brain. With more than 750,000 Canadians currently living with cognitive impairment, and a rapidly aging population, there has never been a greater need to understand the causes of cognitive decline and dementia. 

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