Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 90, Issue 2, Pages 535-542Publisher
IOS PRESS
DOI: 10.3233/JAD-220359
Keywords
Aging; Apolipoproteins E; amyloid; cardiovascular system; cerebrovascular circulation; cognition; female; hemodynamics; ultrasound
Categories
Funding
- Eunice Kennedy Shriver National Institute of Child Health & Human Development
- National Institute on Aging of the National Institutes of Health [P30 AG072973, P30AG035982, R01 AG043962, UL1TR000001, K99 AG075255]
- American Heart Association [16GRNT30450008]
- Georgia Holland Endowment Fund
- Leo and Anne Albert Charitable Trust
- Ann and Gary Dickinson Family Charitable Foundation
- Lilly Pharmaceuticals
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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.
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.
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