Populations with modifiable risk factors for dementia identified

A new study pinpoints three sub-groups of individuals in their early 60’s who have an observable risk for dementia that they and their clinicians can still do something about.

“The findings from this study may help to better predict an individual’s risk in order to plan a personalized prevention strategy to slow down the onset of dementia,” says Lisa Xiong, lead author of the study and a PhD candidate in Clinical Pharmacology with the Dr. Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Research Institute.

In 2020, the Lancet Commission identified 12 modifiable factors that increase population-level dementia risk: low education, hearing impairment, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking history, depression, social isolation, physical inactivity, air pollution, and diabetes. It was unclear if these risk factors co-occur among individuals in a way that could help clinicians point out the people in the population who may need extra attention.

“We aimed to describe the different ways in which individuals develop dementia by identifying underlying profiles, or subpopulation groups, based on the Lancet Commission’s modifiable risk factors, and we found them,” says Ms. Xiong.

The researchers used data from the UK Biobank, an observational study of over 500,000 participants living in the United Kingdom, to identify subgroups of people based on their modifiable dementia risk factors in dementia-free adults who were aged 60–64 years at the start of the UK study. They then utilized these participants’ data, collected over 15 years of follow up, to examine their risks of developing dementia.

Published in the journal Molecular Psychiatry, the researchers found distinct “risk profiles” – or sub-groups of individuals related to their risk factors – as follows: cardiometabolic (heart health) risk, substance use-related risk, and a low-risk category of people who had fewer of these risk factors for dementia.

“Understanding how these distinct combinations of factors together drive dementia allows for a more personalized (or a more person-centered approach to) risk assessment and may lead to targeted strategies for prevention and treatment,” says Dr. Walter Swardfager, senior author of the study and a scientist in the Hurvitz Brain Sciences Research Program at Sunnybrook Research Institute.

The researchers also used the results of cognitive tests and brain imaging to understand how the profiles set the stage for dementia. The cognitive tests revealed that the profiles had different levels of brain function such as thinking, learning, remembering, and using judgement and language, while brain imaging showed different amounts of brain shrinkage and damage to the white matter.

“The three risk groups showed unique characteristics on both brain imaging and cognitive testing, showing how individuals can be at risk for developing dementia in different ways,” says Dr. Swardfager, also an assistant professor in the Department of Pharmacology and Toxicology at the University of Toronto.

Some of the characteristics of the three profiles differed between the sexes, and interactions between these profiles and their genetic susceptibility for Alzheimer’s disease were observed to influence dementia outcomes. Up to 50 per cent of one’s dementia risk is based on their genes, reflecting an important contribution that can be inherited from parents.

“The study illustrates how complex interactions between genetic and modifiable risk factors for dementia manifest in traits that we can observe many years before dementia develops, providing a new opportunity to modify the disease trajectory,” adds Dr. Swardfager.

The authors advocate for further development of these dementia risk prediction tools to advance personalized risk assessments and personalized medicine approaches; including a need to examine multi-domain dementia risk in different racial/ethnic groups.

The research team was a collaboration from Sunnybrook Health Sciences Centre, University of Toronto, Ottawa Heart Institute, University of Ottawa, Østfold University College (Halden, Norway), and Toronto Rehabilitation Institute (UHN).