Potentially Modifiable Risk Factors for Low Cognition and Dementia in Canada

Cognitive impairment and dementia are a multifactorial process involving several pathological mechanisms beyond neurodegeneration. Dementia is characterized by severe and progressive cognitive impairment affecting daily livings. In Canada, over 600,000 people live with dementia, and its consequences are catastrophic. However, estimates suggest that 35% to 45% of dementia cases worldwide are attributable to 9 to 14 modifiable risk factors. The primary objective of this dissertation was to estimate the dementia prevention potential in Canada associated with well-established modifiable risk factors in Canada using the Canadian Longitudinal Study on Aging, a nation-wide longitudinal cohort of 30,097 adults. We found that 50% of dementia cases in Canada were attributable to 12 risk factors, with physical inactivity, obesity, hypertension, and hearing loss being the most prominent. Recent lifestyle intervention trials showed that it is possible to improve cognition by combating combinations of risk factors. To help identify risk profiles of individuals most likely to benefit from these interventions, the second objective was to identify risk factor combinations that are both highly prevalent and strongly associated with low cognition. The dyadic combination of hearing loss and physical inactivity (Cohen’s effect size d = -0.21) was most strongly associated with low cognition, followed by adding hypertension for the triad (d = -0.25), and adding obesity for the tetrad (d = -0.27). The synergistic interaction effect observed between hypertension and physical inactivity supports the rationale of joint prevention efforts on both vascular and brain health. The third objective was to identify combinations that are both highly prevalent and have the largest cognitive detrimental effect over 3 years. The combination of hearing loss with physical inactivity was the most prevalent dyad with the largest effect size (d = -0.28) and a synergistic effect. For the triad, the combination of hearing loss, physical inactivity, and hypertension had the greatest effect (d = -0.28), while the tetrad included hearing loss, physical inactivity, hypertension, and sleep disturbance (d = -0.20). Altogether, this dissertation highlights, for the first time, that up to 50% of dementia cases in Canada could be prevented by targeting specific risk factors, with hearing loss and physical inactivity being those that would yield the largest effect size if addressed.