A randomized controlled trial examining the effect of aerobic exercise on cognitive decline and brain region volumes in older men and women with mild cognitive impairment: Possible interaction between sex and BDNF polymorphisms

Michael Smith Foundation for Health Research/ Pacific Alzheimer Research Foundation Post-Doctoral Fellowship Award

Worldwide, one new case of dementia is detected every four seconds; there is currently no effective drug therapy. Given the greater prevalence of Alzheimer's disease and its faster rate of progression from mild cognitive impairment to Alzheimer's disease in women compared to men, it is essential to assess sex differences in studies relating to dementia to foster development of successful sex-specific, non-pharmacological interventions.

Results from randomized controlled trials in older adults suggest that aerobic training can enhance functioning in certain cognitive domains. Importantly, exercise efficacy differs by sex, with women showing greater cognitive changes. The sex difference may be related to brain derived neurotrophic factor (BDNF), a growth factor involved in brain health and a mediator of the cognitive-enhancing effects of aerobic training. Women, compared to men, have greater declines in BDNF with increasing age.

The beneficial effects of aerobic training on cognitive decline are modified by the Val66Met polymorphism in the BDNF gene, which leads to altered secretion of BDNF. Furthermore, aerobic training alters stress hormones differently in women and men, and women Val66Met carriers have heightened stress responses compared to men.

The main aim of this project is to determine whether sex and the BDNF polymorphism influence aerobic training efficacy in ameliorating cognitive decline and brain tissue atrophy in older people with mild cognitive impairment, a risk factor for dementia. We will also consider whether the beneficial effects of aerobic training might be mediated through alterations in stress hormones in a sex- and Val66Met-dependent manner.

We will share the results of the effectiveness of aerobic training with practitioners and with policy makers in institutions such as Vancouver Coastal Health during educational sessions to help improve patient treatment and care.