Interactions between physical exercise, associative memory, and genetic risk for Alzheimer's disease

The epsilon 4 allele of the APOE gene heightens the risk of late onset Alzheimer's disease. epsilon 4 carriers, may exhibit cognitive and neural changes early on. Given the known memory-enhancing effects of physical exercise, particularly through hippocampal plasticity via endocannabinoid signaling, here we aimed to test whether a single session of physical exercise may benefit memory and underlying neurophysiological processes in young epsilon 3 carriers (epsilon 3/epsilon 4 heterozygotes, risk group) compared with a matched control group (homozygotes for epsilon 3). Participants underwent fMRI while learning picture sequences, followed by cycling or rest before a memory test. Blood samples measured endocannabinoid levels. At the behavioral level, the risk group exhibited poorer associative memory performance, regardless of the exercising condition. At the brain level, the risk group showed increased medial temporal lobe activity during memory retrieval irrespective of exercise (suggesting neural compensatory effects even at baseline), whereas, in the control group, such increase was only detectable after physical exercise. Critically, an exercise-related endocannabinoid increase correlated with task-related hippocampal activation in the control group only. In conclusion, healthy young individuals carrying the epsilon 4 allele may present suboptimal associative memory performance (when compared with homozygote epsilon 3 carriers), together with reduced plasticity (and functional over-compensation) within medial temporal structures.