Sex Differences in Alzheimer’s Disease Neuroimaging Biomarkers among Cognitively Normal Older Adults

Two thirds of Alzheimer’s disease (AD) patients are women. Genetic, medical, and hormonal AD risk factors affect women more negatively compared to men. This exploratory multimodal neuroimaging study aimed to examine sex differences in cognitively normal older adults on: (1) Amyloid-β on 18F-AV-45 Florbetapir PET imaging (2) neurodegeneration via T1 weighted MRI volumetrics, (3) cerebral blood flow via ASL-MRI. We identified genetic (APOE genotype status) and medical (fasting glucose, mean arterial pressure, waist-to-hip ratio, and android and gynoid body fat percentages) AD risk factors associated with the neuroimaging outcomes with observed sex differences. Participants were sedentary older adults (N = 112, ages 65-87 years) without evidence of cognitive decline (CDR = 0) and with elevated cerebral amyloid-β levels (SUVR = 7.27). Multivariate analysis of covariance models adjusted for age, education, and modality specific confounders demonstrated lower volume (F (5, 103) = 13.56, p = <0.001) and higher blood flow F (7, 102) = 2.58, p = 0.017) among women compared to men in AD pathology and estrogen receptor network regions of interest. No sex differences in amyloid-β levels were revealed. Non-optimal fasting glucose, higher android fat percentage, and APOE ε4 carrier status were most strongly associated with lower volume and higher blood flow among women. Our findings suggest genetic and medical risk factors predict sex-specific AD biomarkers. An underlying sex-specific biological pathway may explain these findings however more studies considering reproductive health are needed. Our findings highlight the importance of considering sex differences when developing effective modifiable AD interventions.

Grantor dc:publisher

University of Kansas

Year dc:date.issued

2023

Author dc:creator

• Losinski, Genna

Advisor dc:contributor.advisor

• Watts, Amber

• Clinical psychology
• biomarkers
• neuroimaging
• preclinical Alzheimer's disease
• risk factors
• sex differences

Statement dc:rights

• Copyright held by the author.

Language dc:language.iso

en

Dc Identifier Other

http://dissertations.umi.com/ku:18802

OAI identifier oai:identifier

oai:kuscholarworks.ku.edu:1808/38791