Some underlying mechanisms have been suggested for the protective effects of physical activity against cognitive decline and Alzheimer's disease, including an increased release of neurotrophins; a reduction in cortisol levels; an increased supply of oxygen and nutrients resulting from increased blood flow; improvement of various cardiovascular risk factors, such as hypertension and diabetes mellitus; and a reduction in the risk of cardiovascular and cerebrovascular disease.60 Here, BDNF is linked to early-onset autosomal dominant Alzheimer disease.