Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study. Issue 11 (November 2021)

• Record Type: Journal Article
• Authors: Wang, Rui; Oh, Jennifer M; Motovylyak, Alice; Ma, Yue; Sager, Mark A; Rowley, Howard A; Johnson, Kevin M; Gallagher, Catherine L; Carlsson, Cynthia M; Bendlin, Barbara B; Johnson, Sterling C; Asthana, Sanjay; Eisenmenger, Laura; Okonkwo, Ozioma C
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 41:Issue 11(2021)
• Page Start: 3016
• Page End: 3027
• Publication Date: 2021-11
• Subjects: Cerebral perfusion -- Alzheimer's disease -- chromosomal sex -- APOE gene -- cardiometabolic measurements; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X211021313
• Languages: English
• ISSNs: 0271-678X

Abstract

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40—89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE- genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13—8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (β=−1.43), hippocampus (−1.25), superior frontal gyrus (−1.70), middle frontal gyrus (−1.99), posterior cingulate (−2.46), and precuneus (−2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE -ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE -genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.