Increased Hippocampal Blood Flow in Sedentary Older Adults at Genetic Risk for Alzheimer's Disease

Article type: Research Article

Authors: Zlatar, Zvinka Z.^{a; b} | Wierenga, Christina E.^{a; c; *} | Bangen, Katherine J.^{a; b} | Liu, Thomas T.^{d; e; f} | Jak, Amy J.^{a; c}

Affiliations: [a] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [b] Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA | [c] VA San Diego Healthcare System, La Jolla, CA, USA | [d] Center for Functional Magnetic Resonance Imaging, University of California San Diego, La Jolla, CA, USA | [e] Department of Radiology, University of California San Diego, La Jolla, CA, USA | [f] Department of Bioengineering, University of California San Diego, La Jolla, CA, USA

Correspondence: [*] Correspondence to: Christina E. Wierenga, PhD, VA San Diego Healthcare System, 3350 La Jolla Village Drive, Mailcode 151B, San Diego, CA 92161, USA. Tel.: +1 858 552 8585/Ext. 2579; Fax: +1 858 642 1218; E-mail: [email protected].

Abstract: Resting cerebral blood flow (CBF) decreases with age; however regulatory increases in hippocampal CBF have been associated with genetic risk (Apolipoprotein E [APOE] ε4 carriers) for Alzheimer's disease (AD). Although physical activity exerts beneficial effects on CBF in healthy elderly, the effects of sedentary behaviors on CBF remain unknown. We measured resting hippocampal CBF (via arterial spin labeling magnetic resonance imaging) and sedentary time/physical activity (via accelerometry) on 33 cognitively healthy adults (ages 52–81), 9 of which were APOE ε4 carriers. Results indicate that the relationship between sedentary time and CBF in the left hippocampus differs by APOE status, whereby APOE ε4 carriers show higher CBF as a function of longer sedentary time (B = 10.8, SE = 3.17, β = 0.74, t = 3.41, p < 0.01) compared to noncarriers (B = 1.4, SE = 2.7, β = 0.096, t = 0.51, p = 0.61), possibly suggesting a CBF regulatory response to compensate for metabolic alterations in dementia risk. These preliminary data suggest that the relationship between CBF and sedentary time is different in APOE ε4 carriers and noncarriers and that sedentary time may act as a behavioral risk factor for CBF dysregulation in those at genetic risk for developing AD. More research is needed to further understand the role of sedentary behaviors and physical activity on CBF, especially in individuals at genetic risk of developing AD.

Keywords: Apolipoprotein E, arterial spin labeling, biological aging, cerebral blood flow, hippocampus, magnetic resonance imaging, physical activity, sedentary behavior

DOI: 10.3233/JAD-132252

Journal: Journal of Alzheimer's Disease, vol. 41, no. 3, pp. 809-817, 2014