Given the limited success of therapeutic interventions for Alzheimer disease, there is increased interest in understanding whether modifiable factors can help cope with or postpone the appearance of brain pathology. It is estimated that about 35% of Alzheimer risk is modifiable.1,2 Epidemiologic studies have shown that lifetime exposures to higher education, higher occupational attainment, and cognitively stimulating activities are associated with reduced risk of Alzheimer dementia.3 Autopsy studies have shown interindividual differences in the amount of brain pathology people can tolerate before manifesting cognitive impairments, and autopsied brains of about one-third of individuals who are cognitively normal meet neuropathological criteria for Alzheimer disease.4 About a decade ago, the concept of cognitive reserve was proposed to account for the discrepancy between brain pathology and cognitive status.5 The broad hypothesis was that individuals with enriched lifelong exposures would be able to better tolerate with brain pathology in late life. Many studies have investigated how one can cope with brain damage using proxies of neurodegeneration or synaptic integrity. However, the gold standard for testing the reserve hypothesis is the direct measurement of brain pathology at autopsy.
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Villeneuve S. Lifespan Cognitive Reserve—A Secret to Coping With Neurodegenerative Pathology. JAMA Neurol. 2019;76(10):1145–1146. doi:10.1001/jamaneurol.2019.2899
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