Can frailty influence who gets Alzheimer’s disease?

The following is a guest post by Lindsay Wallace, a CCNA trainee working under the supervision of Dr. Melissa Andrew.

Lindsay Wallace is a doctoral candidate and trainee within the CCNA, working under the supervision of Dr. Melissa Andrew

By 2031, 1.4 million Canadians are expected to have some form of cognitive impairment.

As the leading cause of dementia, the impact of Alzheimer’s disease on those living with the illness, families, care providers, the health care system, and the economy is enormous. At a recent global meeting on dementia, former World Health Organization Director-General Dr. Margaret Chan said she could “think of no other disease where innovation, including breakthrough discoveries to develop a cure, is so badly needed.”

To date, drug therapies have not been successful in stopping the progression of the disease – possibly because they only target the plaques and tangles in the brain that have long been associated with Alzheimer’s disease. We now know that plaques and tangles are not always a reliable source for who ends up with dementia. Many people are diagnosed with Alzheimer’s disease and end up having very few plaques and tangles, whereas others have no cognitive impairment at all, but appear to have many plaques and tangles.

We also know that the majority of people who are diagnosed with dementia are older, and have many other health problems. Unfortunately, this same group of people is often excluded from clinical trials of Alzheimer’s disease drugs because their other conditions are thought to complicate the understanding of how the disease develops.

In light of these findings, our research team – working within the Canadian Consortium on Neurodegeneration in Aging – is guided by the assumption that the frailer a person is (or the more health problems they have) the more vulnerable they will be to developing an additional health problem. In particular, our group is investigating the progression of neurodegenerative disease, such as Alzheimer’s, to understand how frailty may influence its development, and thereby find effective strategies for its prevention and treatment.

Our most recent work suggests that frailty might make individuals more vulnerable to dementia by lowering the threshold of plaques and tangles necessary to produce dementia. In other words, for people who are frail, fewer plaques and tangles may be necessary to produce the cognitive impairment characteristic of dementia. For example, in two people who have the same amount of plaques and tangles, the person who is frailer will be more likely to develop dementia. If this is the case, it means that we can treat frailty – as early as middle age – to reduce the risk of dementia.

So far, promising treatments for frailty target multiple lifestyle factors, including exercise, nutrition, psychological well-being, and social engagement. More research is needed to fully understand how frailty might influence the disease process in Alzheimer’s and other forms of dementia so that we can target treatments in the most effective way. Our team is continuing our work in this area, as well as other key areas, including polypharmacy in people with dementia, and how sex and gender influence dementia risk.

To learn more about this exciting work, visit the CCNA’s news section where updates are posted.

The views and opinions expressed in this guest blog are those of the authors (individual CCNA scientists) and do not necessarily reflect the views of the Canadian Consortium on Neurodegeneration in Aging and its partner organizations.