Examining Alzheimer's Disease Modifiable Risk Factors: Impact of Physical Activity and Diet on Neuroanatomy and Behaviour in Mice

Dementia, a global public health challenge, is significantly influenced by lifestyle factors such as obesity. This study examines the impact of obesity and intervention approaches -physical exercise, a low-fat diet, or both- on brain structure in a triple-transgenic mouse model of Alzheimer's disease (3xTgAD) and wild-type mice fed a high-fat diet. Volumetric and deformation-based morphometry analyses showed significant neuroanatomical differences related to genotype and a high-fat diet, particularly affecting the hippocampus and cerebellum. Diet and exercise interventions partially mitigate these effects. Volume changes were correlated with behavioural data, producing a unique brain-behaviour signature tied to intervention-driven neuroanatomy improvements. This pattern was correlated with gene expression patterns, identifying modules of genes related to metabolic processes such as glucose homeostasis and fatty acid transportation. Overall, interventions promote changes that seem to counteract some of the effects of a high-fat diet, influencing biological processes that support brain health.