Tiny Strokes May Cause Dementia

A U of T research team may have identified a previously unknown – yet potentially major – cause of dementia in older adults.

Alzheimer’s disease is the most common form of dementia in Canada. But more than half of people over age 65 have leukoaraiosis, a gradual and permanent degeneration of the nerve fibres, or white matter, in the brain. At an early stage it isn’t considered problematic. But as leukoaraiosis progresses, it’s associated with cognitive decline and eventually dementia. (The presence of leukoaraiosis also worsens the symptoms of existing Alzheimer’s.)

It was once assumed that this degeneration was a normal part of the aging process, as arteries in the brain narrowed over time and restricted the blood flow. Dr. Daniel Mandell, a professor in U of T’s department of medical imaging, suspected there might be another cause.

Led by Mandell, researchers at the University Health Network’s Krembil Neuroscience Centre recruited five individuals with white-matter damage in their brains and followed them with weekly MRI scans for 16 weeks. In three of the individuals, the team saw very small areas of white matter that swelled temporarily, indicating that tiny “silent” strokes occurred – silent, because they caused no symptoms. Within a week or two, all MRI evidence of the strokes was gone. But new white-matter disease developed in those same brain regions, suggesting that the strokes had precipitated it.

No events were observed in the other two individuals – though this doesn’t mean that their white-matter disease isn’t caused by strokes. “It’s conceivable there were smaller ones we’re not able to see,” says Mandell. It’s also possible those patients didn’t happen to have strokes during this 16-week period.

Although strokes this size in the white matter normally go undetected and untreated, they can potentially be prevented. “The diagnosis is not such a challenge,” says Mandell. “The challenge is what causes it, and whether we can do anything about it.” High blood pressure has already been established as the strongest modifiable risk factor for leukoaraiosis. There’s also some evidence that smoking and diabetes may have an impact. It suggests this form of dementia could be prevented or slowed down with medications and lifestyle changes. “There aren’t a lot of treatable causes of cognitive decline,” Mandell notes. “It’s exciting.”

His work demonstrates a new way to experiment with prevention strategies, including the use of blood pressure medications. “With this biomarker of tiny strokes over 16 weeks, we can test novel therapies and follow people just for a month or two, and see if there’s a difference on the tiny strokes they’re having.”

A separate meta-analysis by a U of T PhD candidate in psychology last year found that leukoaraiosis affects more brain functions than most experts realize. Since these changes occur slowly and in many areas, they can go unnoticed at first or be chalked up to old age. “Sometimes it’s difficult to measure mild, early cognitive decline,” says Mandell. It’s another vote for the importance of prevention.

Mandell hopes to repeat the study with a larger sample size.