Brain health in older adults: At the crossroads of frailty and resilience.

Brain health is a state of physiological functioning of the organ that allows individuals to fully achieve their age-related potential. Throughout life, a wide range of endogenous and exogenous factors can influence positively and negatively brain health. Among them, age is undoubtedly one of the most important, particularly for its effect on brain's cognitive functions. Pathological cognitive decline is characterized by anatomical changes in areas involved in memory, execution, and reasoning, which may result from various mechanisms such as mitochondrial dysfunction, altered proteostasis, and neuroinflammation. Clinically age-dependent pathologic cognitive decline initially manifests as mild cognitive impairment, which can then progress to full dementia. Dementia is a clinical syndrome with several possible underlying causes, of which Alzheimer's disease, pathologically defined by amyloid-β and tau accumulation, is the most frequent. Although the causes of dementia are unknown, two major classes of risk factors have been identified: unmodifiable and modifiable. Unmodifiable risk factors include age, gender, and genes such as apolipoprotein E4. Among the modifiable one's diet, smoking habit, physical inactivity, and social isolation. Importantly, these two classes of risk factors are not independent from each other but interact continuously to shape an individual's overall risk trajectory. Recent evidence suggests that up to 45% of dementia cases could be prevented or delayed by correcting these modifiable risk factors. To achieve this goal the four cardinal points of behavioral health, which include nutrition, exercise, socialization and wellness, should be implemented as a framework for brain health, healthy brain aging and cognitive resilience.