Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

Dementia is one of the most pressing health care issues of the 21st century and no effective drug treatment exists. However, exercise can reduce memory decline and may be an effective treatment for dementia. Importantly, studies suggest that older women benefit more from exercise than men. To harness exercise's ability to combat dementia it is vital to discover why women show greater beneficial effects of exercise on brain health. Women are also more likely to be diagnosed with Alzheimer's Disease (AD), irrespective of the fact that they live longer than men. Half of older people diagnosed with Mild Cognitive Impairment (MCI) will transition into AD and women progress from MCI to AD at a faster rate than men. Thus factors that reduce the conversion of MCI to AD are sought after and exercise is one such factor. Our research aims to understand the mechanisms behind the ability of exercise to ameliorate cognitive decline more in women with MCI compared to men with MCI. We will examine how biological sex coupled with stress, inflammation and hormones are altered after exercise and whether genetic differences contribute to the effects of exercise to promote memory. We will focus on one particular protein called brain derived neurotrophic factor (BDNF), which is involved in brain health and is a mediator of the cognitive-enhancing effects of exercise. Importantly, there is an alteration within the BDNF gene is some humans that alters the levels of this protein. This alteration in BDNF may influence exercise's ability to promote brain health in women more so than men. We will use clinical and preclinical models to examine the effects of sex, genetics and hormones on the ability of exercise to influence brain structure and memory. Although sex differences exist in AD, research targeting sex as a factor is scarce. Our program will be vital in filling this knowledge gap and will foster the development of tailored, personalized treatments for cognitive decline in both sexes.