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

Article type: Short Communication

Authors: Palmer, Jacqueline A.^{a; b} | Kaufman, Carolyn S.^c | Vidoni, Eric D.^b | Honea, Robyn A.^b | Burns, Jeffrey M.^b | Billinger, Sandra A.^{a; b; c; *}

Affiliations: [a] Department of Neurology, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA | [b] University of Kansas Alzheimer’s Disease Research Center, Fairway, KS, USA | [c] Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA

Correspondence: [*] Correspondence to: Sandra A. Billinger, PT, PhD, FAHA, Department of Neurology, School of Medicine, University of Kansas Medical Center, Kansas City, KS, USA. E-mail: [email protected].; Twitter: @Sandy_REACHlab

Abstract: Sex as a biological variable appears to contribute to the multifactorial etiology of Alzheimer’s disease. We tested sex-based 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-β deposition yet achieved similar cognitive performance to males and female noncarriers. Further, female APOE4 carriers with robust cerebrovascular responses to exercise possessed lower amyloid-β. 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.

Keywords: Aging, Apolipoproteins E, amyloid, cardiovascular system, cerebrovascular circulation, cognition, female, hemodynamics, ultrasound

DOI: 10.3233/JAD-220359

Journal: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 535-542, 2022