Pathways of Prevention: A Scoping Review of Dietary and Exercise Interventions for Neurocognition.

Alzheimer's disease and related dementias (ADRD) represent an increasingly urgent public health concern, with an increasing number of baby boomers now at risk. Due to a lack of efficacious therapies among symptomatic older adults, an increasing emphasis has been placed on preventive measures that can curb or even prevent ADRD development among middle-aged adults. Lifestyle modification using aerobic exercise and dietary modification represents one of the primary treatment modalities used to mitigate ADRD risk, with an increasing number of trials demonstrating that exercise and dietary change, individually and together, improve neurocognitive performance among middle-aged and older adults. Despite several optimistic findings, examination of treatment changes across lifestyle interventions reveals a variable pattern of improvements, with large individual differences across trials. The present review attempts to synthesize available literature linking lifestyle modification to neurocognitive changes, outline putative mechanisms of treatment improvement, and discuss discrepant trial findings. In addition, previous mechanistic assumptions linking lifestyle to neurocognition are discussed, with a focus on potential solutions to improve our understanding of individual neurocognitive differences in response to lifestyle modification. Specific recommendations include integration of contemporary causal inference approaches for analyzing parallel mechanistic pathways and treatment-exposure interactions. Methodological recommendations include trial multiphase optimization strategy (MOST) design approaches that leverage individual differences for improved treatment outcomes.