Phenotypic heterogeneity of obesity‐related brain vulnerability: one‐size interventions will not fit all

Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures. We present a selective, narrative review of evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity‐related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline. Intact memory and problem solving are key to functional independence and quality of life in older age. Here, we review evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity‐related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline.