Sex Differences in Resilience and Resistance to Brain Pathology and Dysfunction Moderated by Cerebrovascular Response to Exercise and Genetic Risk for Alzheimer's Disease

Sex as a biological variable appears to contribute to the multifactorial etiology of Alzheimer's disease. We tested sexbased interactions between cerebrovascular function and APOE4 genotype on resistance and resilience to brain pathology and cognitive executive dysfunction in cognitively-normal older adults. Female APOE4 carriers had higher amyloid-beta deposition yet achieved similar cognitive performance to males and female noncarriers. Further, female APOE4 carriers with robust cerebrovascular responses to exercise possessed lower amyloid-beta. These results suggest a unique cognitive resilience and identify cerebrovascular function as a key mechanism for resistance to age-related brain pathology in females with high genetic vulnerability to Alzheimer's disease.

Automated summary

Sex as a biological variable affects the etiology of Alzheimer's disease. The study found that cerebrovascular function is a key mechanism for resistance to age-related brain pathology for female APOE4 carriers.