Cognitive impairment and its severe form dementia are progressively prevalent in older adults and loom as a public health adversity unless effective interventions are developed. Cognitive impairment is a convergent trait caused by injury from an idiosyncratic mix of four prevalent diseases (Alzheimer disease; vascular brain injury; Lewy body diseases, such as Parkinson disease and dementia with Lewy bodies; and limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy) that is balanced by distinctly varying resilience, which is included of reserve and reward. Brain regional damage from each of these four predominant diseases is generated by the net effect of injury and (mal)adaptive response and is attended by characteristic lesions. Brain regional injury is generated by the net effect of injury and (mal)adaptive response. The extent to which signs and symptoms of such damage occur is influenced by an fundamental flexibility comprising reserve and reward. Finding personalized interferences that target specific mechanisms of damage likely yields the most effective therapies.

Keywords : Cognitive Impairment, Traumatic Brain Injury, Brain, Dementia, Parkinson’s Disease, Alzheimer’s Disease, Mild Cognitive Impairment.