Associations between age, sex, APOE genotype, and regional vascular physiology in typically aging adults

• Published in: NeuroImage (Orlando, Fla.) Vol. 275; p. 120167
• Main Authors: Damestani, Nikou L., Jacoby, John, Yadav, Shrikanth M., Lovely, Allison E., Michael, Aurea, Terpstra, Melissa, Eshghi, Marziye, Rashid, Barnaly, Cruchaga, Carlos, Salat, David H., Juttukonda, Meher R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2023; Elsevier Limited; Elsevier
• Subjects: Adult; Age; Aged; Aged, 80 and over; Aging; Aging - genetics; Alzheimer's disease; APOE; Apolipoprotein E; Apolipoproteins E - genetics; Arterial spin labeling; Arterial transit time; Blood flow; Blood pressure; Brain - physiology; Cerebral blood flow; Cerebrovascular Circulation - genetics; Cross-Sectional Studies; Female; Genotype; Genotype & phenotype; Genotypes; Healthy aging; Hemodynamics; Humans; Life span; Magnetic Resonance Imaging; Male; Middle Aged; Neurodegenerative diseases; Perfusion; Perfusion MRI; Physiology; Regions; Risk factors; Sex; Sex differences; Spin Labels; ATT; Perfusion MRI; MRI; CBF; Sex differences; PLD; pCASL; TFCE; Cerebral blood flow; FDR; FWE; Arterial spin labeling; Aging; APOE; Healthy aging; Arterial transit time; HCP-A
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2023.120167

Altered blood flow in the human brain is characteristic of typical aging. However, numerous factors contribute to inter-individual variation in patterns of blood flow throughout the lifespan. To better understand the mechanisms behind such variation, we studied how sex and APOE genotype, a primary genetic risk factor for Alzheimer's disease (AD), influence associations between age and brain perfusion measures. We conducted a cross-sectional study of 562 participants from the Human Connectome Project - Aging (36 to >90 years of age). We found widespread associations between age and vascular parameters, where increasing age was associated with regional decreases in cerebral blood flow (CBF) and increases in arterial transit time (ATT). When grouped by sex and APOE genotype, interactions between group and age demonstrated that females had relatively greater CBF and lower ATT compared to males. Females carrying the APOEε4 allele showed the strongest association between CBF decline and ATT incline with age. This demonstrates that sex and genetic risk for AD modulate age-associated patterns of cerebral perfusion measures.