Interaction of Age and APOE Genotype on Cerebral Blood Flow at Rest

Article type: Research Article

Authors: Wierenga, Christina E.^{a; b; c; *} | Clark, Lindsay R.^d | Dev, Sheena I.^a | Shin, David D.^e | Jurick, Sarah M.^c | Rissman, Robert A.^f | Liu, Thomas T.^e | Bondi, Mark W.^{g; b}

Affiliations: [a] Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA | [b] Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA | [c] Veterans Medical Research Foundation, San Diego, CA, USA | [d] San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA | [e] Department of Radiology, School of Medicine, University of California, San Diego, La Jolla, CA, USA | [f] Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, USA | [g] Psychology Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA

Correspondence: [*] Correspondence to: Christina Wierenga, Ph.D., VA San Diego Healthcare System, 3350 La Jolla Village Drive, Mailcode (151B), San Diego, CA 92161, USA. Tel.: +1858 552 8585; Ext: 2579, Fax: +1858 642 1218, E-mail: [email protected].

Abstract: We investigated the impact of APOE genotype on cerebral blood flow (CBF) in older and younger adults. Forty cognitively normal older adults (16 ε4 carriers, 24 non-ε4 carriers) and 30 younger adults (15 ε4 carriers, 15 non-ε4 carriers) completed a resting-state whole-brain pulsed arterial spin labeling magnetic resonance scan. Main effects of aging were demonstrated wherein older adults had decreased gray matter CBF corrected for partial volume effects compared to younger adults in widespread brain regions. Main effects of APOE genotype were also observed wherein ε4 carriers displayed greater CBF in the left lingual gyrus and precuneus than non-carriers. An interaction between age and APOE genotype in the left anterior cingulate cortex (ACC) was characterized by reduced CBF in older ε4 carriers and increased CBF in young ε4 carriers. Increased CBF in the left ACC resulting from the interaction of age group and APOE genotype was positively correlated with executive functioning in young ε4 adults (r = 0.61, p = 0.04). Results demonstrate APOE genotype differentially impacts cerebrovascular function across the lifespan and may modify the relationship between CBF and cognition. Findings may partially support suggestions that the gene exerts antagonistic pleiotropic effects.

Keywords: Aging, antagonistic pleiotropy, apolipoprotein E, cerebral blood flow, cerebrovascular function

DOI: 10.3233/JAD-121897

Journal: Journal of Alzheimer's Disease, vol. 34, no. 4, pp. 921-935, 2013