Brain Longevity

Even those who do not experience dementia or mild cognitive impairment may experience subtle cognitive changes associated with aging, which can affect an older adult's everyday function and quality of life. ^[1] Morphologically, brain aging is primarily characterized by brain volume loss, cortical thinning, white matter degradation, loss of gyrification, and ventricular enlargement. ^[2] Preservation of brain health is a worldwide priority, and an increasing body of evidence has unveiled a previously under-recognized contribution of peripheral organs to brain dysfunction and damage. ^[3]

During aging, the brain exhibits signs of compromised bioenergetics, impaired adaptive neuroplasticity and resilience, aberrant neuronal network activity, dysregulation of neuronal calcium homeostasis, accrual of oxidatively modified molecules and organelles, and inflammation, which render it vulnerable to Alzheimer's and Parkinson's diseases and stroke. ^[4] Accumulated oxidative stress may be one of the key mechanisms causing cognitive aging and neurodegenerative diseases such as Alzheimer's disease. ^[5] Neuroplasticity, the brain's capacity to reorganize itself by forming new neural connections, continues throughout the lifespan and supports learning, memory, and recovery from injury or disease. ^[6]

Lifestyles that include intermittent bioenergetic challenges such as exercise, fasting, and intellectual challenges foster healthy brain aging, whereas sedentary overindulgent lifestyles accelerate brain aging. ^[4] Higher levels of cognitive reserve are associated with better cognitive performance and a reduced risk of incident mild cognitive impairment or dementia, and reserve can be enhanced throughout the lifespan. ^[7] Exercise has many beneficial effects on brain health, contributing to decreased risks of dementia, depression and stress, and has a role in restoring and maintaining cognitive function, in part through a muscle-brain endocrine loop. ^[8]

Neuroimaging-based brain age can serve as a biomarker of an individual's brain health, and having an older-appearing brain relates to advanced physiological and cognitive ageing and the risk of mortality. ^[9] Of currently available therapeutics for cognitive aging, long-term physical activity is proposed as the most promising avenue for improving cognitive health by reducing reactive oxygen species while promoting the low levels required for optimal function. ^[5] Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients suggest a future in which specific anti-Alzheimer's therapy is combined with lifestyle interventions targeting general brain health. ^[10] The 2024 primary prevention of stroke guideline aligns its recommendations with the American Heart Association's Life's Essential 8 for optimizing cardiovascular and brain health across the lifespan. ^[11]