Antioxidants Combined with Behavioral Enrichment Can Slow Brain Aging

Abstract

In the brain, oxidative damage, loss of synapses, and loss of growth factors such as brain-derived neurotrophic factor (BDNF) are linked to age-associated cognitive decline and Alzheimer's disease (AD). Antioxidant treatments to reduce oxidative damage have provided only modest benefits in human clinical trials. Cognitive and physical training, which may promote synapse growth and maintenance and increase BDNF, has proved to be more promising in small clinical trials in normal aged individuals and AD patients. Using a canine model of human brain aging, which naturally accumulates oxidative damage and cognitive dysfunction, we tested the hypothesis that combining treatments that can reduce several age-associated neuropathologies will prove to he more efficacious than targeting a single pathologic cascade. Aged beagles were either fed an antioxidant/mitochondrial cofactor diet (vitamins E and C, fruits and vegetables, lipoic acid and carnitine) or provided with behavioral enrichment that can increase BDNF and synapse and neuron growth (environmental, social, and cognitive enrichment with physical exercise) or treated with a combination of both the diet and behavioral enrichment. Cognitive improvements were observed for each treatment alone, but the combination approach, in particular, led to larger improvements in learning scores, to maintenance of cognitive ability, and to recovery of impaired memory function. Notably, each treatment selectively reduced different types of neuropathology in the brain. The use of a combination of antioxidant supplement or diet and other lifestyle modifications (increased social activity, physical activity, and cognitive engagement) may work additively and be beneficial for healthy human brain aging.