Amyloid plaques and tangles in the brain are a major risk factor in Alzheimer’s disease, but just because a person has a lot of them doesn’t mean they will have dementia. So if the amyloid burden alone doesn’t predict the severity of disease, what other factors are at play?
Dalhousie researchers Lindsay Wallace and Kenneth Rockwood uncovered a risk factor even more important to the development of Alzheimer’s: physical frailty. Their study was published in Lancet Neurology.
To make the link, the researchers carried out a post-mortem examination of 456 adults over 59 years, assessing the burden of amyloid plaques and tangles in their brain tissues. They then compared those results against their dementia symptoms while they were alive, as well as scores for physical frailty — an index based on the accumulation of physical health deficits.
“We confirmed that there are a lot of people with lots of plaques and tangles who don’t have dementia,” said Wallace in a statement.
“These people were less frail. Conversely, there were people with very few plaques and tangles who had severe dementia. These people were very frail… in fact, they were more frail even than the people who had lots of plaques and tangles and dementia.”
That means that physical frailty could be an independent factor in the development of dementia, or it could aggravate the pathology of amyloid plaques. Either way, physical resilience could provide protection against the development of Alzheimer’s.
The results might also explain why recent focus on developing drugs that target amyloid plaques and tangles have had such poor success in clinical trials: the factors that affect the development of Alzheimer’s are more complex than the accumulation of a single protein in the brain.
Given that there is still no treatment to slow the progression of Alzheimer’s on the market, this newly validated risk factor is especially important. It gives people a pathway to reduce their Alzheimer’s risk through lifestyle.
Even low levels of amyloid pathology can lead to Alzheimer’s when people are very frail. But exercise, nutrition, sleep, and disease management are all ways to increase physical resilience.
Beyond drug development, we can immediately begin to target factors that contribute to frailty through community and senior housing design. Encouraging physical activity and healthy eating could be the keys to preventing cognitive decline and helping seniors stay independent.
Overall health is critical to quality of life as we age, and this study provides evidence that a strong and healthy brain thrives best in a resilient body.