Metzler-Baddeley, C (2014 - 2017) How do individual differences in midlife adiposity and APOE genotype as risk factors for dementia affect brain structure and cognition? A cross-sectional MRI study. Alzheimer's Society/BRACE. £305,161.
Obesity and dementia are amongst the largest public health problems in the Western World. There is accumulating evidence that they are linked: Being obese in midlife doubles the risk of developing dementia at a later age. Why this is the case remains unknown. Recently, we demonstrated that being overweight is linked to a weakening (i.e. enhanced diffusivity) of the fornix, a limbic pathway that connects the hippocampus with other brain regions. Hippocampal degeneration is the hallmark feature in people with prodromal Alzheimer’s disease (AD) and in carriers of the APOE ε4 allele with an enhanced genetic risk of developing AD. Our result suggests that it is possible that excessive body fat may lead to changes in the brain that may increase vulnerability to neurodegeneration. However, the relationship between variation in midlife body fat and changes in brain structure is not well understood and it remains unclear whether APOE ε4 modulates this link.
The proposed research aims to expand our understanding of obesity-related changes in the brain and potential interactions with classical risk factors such as APOE genotype. We propose to use novel magnetic resonance imaging techniques that allow us to measure specific properties of white matter microstructure to study the effects of obesity and APOE genotype on brain connections in 120 middle aged individuals ranging from lean to obese. Our results will help to develop MRI biomarkers of midlife risk, which in turn might help predict an individual’s risk of developing dementia many years before the onset of any clinical symptoms at an age where disease prevention may become possible in the future.