The hormone irisin, released during muscle contraction, is a key regulatory factor in enhancing cognitive function in the brain through exercise, and holds promise for the treatment of cognitive decline caused by aging or AD.[264] Furthermore, patients with moderate‐to‐severe AD show reduced levels of FNDC5/irisin in the brain and cerebrospinal fluid, whereas high FNDC5/irisin levels in the brain or periphery improve synaptic and memory impairments in AD mouse models.[265] Therefore, certain exercise intensity is a prerequisite for elevating peripheral irisin levels in the bloodstream. This evidence concerns the gene FNDC5 and Alzheimer disease.