Longitudinal Changes in Serum Glucose Levels are Associated with Metabolic Changes in Alzheimer’s Disease Related Brain Regions

Article type: Research Article

Authors: Burns, Christine M.^{a; b; *} | Kaszniak, Alfred W.^{c; d} | Chen, Kewei^{d; e; f} | Lee, Wendy^{d; e} | Bandy, Daniel J.^{d; e} | Caselli, Richard J.^{d; g} | Reiman, Eric M.^{d; e; h}

Affiliations: [a] Minneapolis Medical Research Foundation, Minneapolis, MN, USA | [b] Department of Neurology, University of Minnesota, Minneapolis, MN, USA | [c] Department of Psychology, University of Arizona, Tucson, AZ, USA | [d] Arizona Alzheimer’s Consortium, Phoenix, AZ, USA | [e] Banner Alzheimer’s Institute, Phoenix, AZ, USA | [f] Department of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ, USA | [g] Mayo Clinic Scottsdale, Scottsdale, AZ, USA | [h] Department of Psychiatry, University of Arizona, Tucson, AZ, USA

Correspondence: [*] Correspondence to: Christine M. Burns, PhD, LP, Research Fellow in Neuropsychology, Minneapolis Medical Research Foundation, Hennepin County Medical Center, 701 Park Ave., Suite PPC4-440, Minneapolis, MN 55415, USA. Tel.: +1 602 585 5686; Fax: +1 612 873 1652; E-mail: [email protected].

Abstract: Background:The association between longitudinal changes in serum glucose level and longitudinal changes in [18F] Fluorodeoxyglucose-PET (FDG PET) measurements of Alzheimer’s disease (AD) risk are unknown. Objective:To investigate whether variation in serum glucose levels across time are associated with changes in FDG PET measurements of cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer’s disease (AD). Methods:Participants are a subset of a prospective cohort study investigating FDG PET, apolipoprotein E (APOE) ɛ4, and risk for AD which includes data from baseline, interim, and follow up visits over 4.4±1.0-years. An automated brain-mapping algorithm was utilized to characterize and compare associations between longitudinal changes in serum glucose levels and longitudinal changes in rCMRgl. Results:This study included 80 adults aged 61.5±5 years, including 38 carriers and 42 non-carriers of the APOE ɛ4 allele. Longitudinal increases in serum glucose levels were associated with longitudinal CMRgl decline in the vicinity of parietotemporal, precuneus/posterior cingulate, and prefrontal brain regions preferentially affected by AD (p < 0.05, corrected for multiple comparisons). Findings remained significant when controlled for APOE ɛ4 status and baseline and advancing age. Conclusions:Additional studies are needed to clarify and confirm the relationship between longitudinal changes in peripheral glucose and FDG PET measurements of AD risk. Future findings will set the stage on the use of FDG PET in the evaluation of possible interventions that target risk factors for the development of AD.

Keywords: Alzheimer’s disease, blood glucose, longitudinal studies, positron emission tomography

DOI: 10.3233/JAD-170767

Journal: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 833-840, 2018