Assessment of Alzheimer's Disease Risk with Functional Magnetic Resonance Imaging: An Arterial Spin Labeling Study

Issue title: Predictive Biomarkers for Alzheimer's Disease using State-of-the-Art Brain Imaging Techniques

Guest editors: Pravat K. Mandal

Article type: Research Article

Authors: Bangen, Katherine J.^a | Restom, Khaled^b | Liu, Thomas T.^b | Wierenga, Christina E.^{a; c} | Jak, Amy J.^{a; d} | Salmon, David P.^e | Bondi, Mark W.^{a; d; *}

Affiliations: [a] Department of Psychiatry University of California, San Diego, School of Medicine, San Diego, CA, USA | [b] Department of Radiology University of California, San Diego, School of Medicine, San Diego, CA, USA | [c] Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA | [d] Psychology Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA | [e] Department of Neurosciences, University of California, San Diego, School of Medicine, San Diego, CA, USA

Correspondence: [*] Correspondence to: Mark W. Bondi, Ph.D., VA San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA 92161, USA. Tel.: +1 858 552 8585 ext. 2809; Fax: +1 858 642 1218; E-mail: mbondi@ucsd.edu.

Abstract: Functional magnetic resonance imaging (fMRI) of older adults at risk for Alzheimer's disease (AD) by virtue of their cognitive (i.e., mild cognitive impairment [MCI]) and/or genetic (i.e., apolipoprotein E [APOE] ε4 allele) status demonstrate divergent brain response patterns during memory encoding across studies. Using arterial spin labeling MRI, we examined the influence of AD risk on resting cerebral blood flow (CBF) as well as the CBF and blood oxygenation level dependent (BOLD) signal response to memory encoding in the medial temporal lobes (MTL) in 45 older adults (29 cognitively normal [14 APOE ε4 carriers and 15 noncarriers]; 16 MCI [8 APOE ε4 carriers, 8 noncarriers]). Risk groups were comparable in terms of mean age, years of education, gender distribution, and vascular risk burden. Individuals at genetic risk for AD by virtue of the APOE ε4 allele demonstrated increased MTL resting state CBF relative to ε4 noncarriers, whereas individuals characterized as MCI showed decreased MTL resting state CBF relative to their cognitively normal peers. For percent change CBF, there was a trend toward a cognitive status by genotype interaction. In the cognitively normal group, there was no difference in percent change CBF based on APOE genotype. In contrast, in the MCI group, APOE ε4 carriers demonstrated significantly greater percent change in CBF relative to ε4 noncarriers. No group differences were found for BOLD response. Findings suggest that abnormal resting state CBF and CBF response to memory encoding may be early indicators of brain dysfunction in individuals at risk for developing AD.

Keywords: Apolipoprotein E, cerebral blood flow, functional, hippocampus, magnetic resonance imaging, memory, mild cognitive impairment

DOI: 10.3233/JAD-2012-120292

Journal: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S59-S74, 2012