FDG PET, Aging and APOE Genotype in Cognitively Normal Persons (S8.006)

OBJECTIVE: To examine associations between 18 F-fluorodeoxyglucose positron emission tomography (FDG PET) and age and to evaluate the impact of carriage of an APOE e4 allele on the association. BACKGROUND: Impact of aging on FDG PET is not well understood, because prior studies have used small numbers of participants. METHODS: We studied 806 cognitively normal (CN), and 70 amyloid-imaging-positive cognitively impaired participants from the Mayo Clinic Study of Aging, Mayo Alzheimer’s Disease Research Center and an ancillary study who had undergone structural MRI, FDG PET and 11 C-Pittsburgh compound B PET. Using partial volume corrected FDG PET glucose uptake ratios, we evaluated associations of regional FDG ratios with age and carriage of an APOE e4 allele in CN participants between the ages of 30 and 95 years. RESULTS: We found modest statistically significant age-related declines in FDG ratio in most cortical and subcortical regions. We also found a main effect of APOE e4 genotype on FDG ratio, with greater uptake in e4 non-carriers compared to carriers, but only in the posterior cingulate/precuneus, lateral parietal, and AD-signature meta-ROI (posterior cingulate/precuneus, lateral parietal and inferior temporal). In age- and sex-matched CN participants the magnitude of the difference in FDG ratio in the AD-signature meta-ROI for APOE e4 carriers compared to non-carriers was about 4 times smaller than the magnitude of the difference between age- and sex-matched elderly APOE e4 carrier CN compared to AD dementia participants. CONCLUSIONS: Glucose metabolism declines with age. APOE e4 allele carriage was associated with FDG ratio reductions in the posterior cingulate/precuneus, lateral parietal, and AD-signature ROIs, and these reductions were present across all ages. The posterior cingulate/precuneus and lateral parietal regions have a unique vulnerability to reductions in glucose metabolic rate as a function both of age and carriage of an APOE e4 allele. Study Supported by: NIH grants P50AG16574, U01AG06786, R01AG11378, Dekelboum Family Foundation, Robert & Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program. Disclosure: Dr. Knopman has received personal compensation for activities with Eli Lilly & Company and TauRx Pharmaceuticals. Dr. Knopman has received personal compensation in an editorial capacity for Neurology. Dr. Knopman has received research support from Janssen and Baxter. Dr. Jack has received personal compensation for activities with Janssen, Eisai Inc., General Electric, Johnson & Johnson, and Eli Lilly & Co. Dr. Jack has received research support from Pfizer Inc., Allon, and Baxter. Dr. Wiste has nothing to disclose. Dr. Lundt has nothing to disclose. Dr. Weigand has nothing to disclose. Dr. Vemuri has nothing to disclose. Dr. Gunter has nothing to disclose. Dr. Lowe has received personal compensation for activities with Bayer Pharmaceuticals Corp. Dr. Lowe has received research support from GE Health Care, Siemens Molecular Imaging, and AVID Radiopharmaceuticals, Inc. Dr. Kantarci has received research support from Pfizer Inc., Jannsen Alzheimer immunotherapy, and Takeda Global Research & Development Center. Dr. Senjem has nothing to disclose. Dr. Mielke has nothing to disclose. Dr. Roberts has received research support from Abbott Laboratories and the Driskill Foundation. Dr. Boeve has received research support from Cephalon, Inc., Allon Therapeutics, and GE Healthcare. Dr. Petersen has received personal compensation for activities with Pfizer, Inc., and Janssen Alzheimer9s Immunotherapy. Dr. Petersen has received royalty payments from Oxford University Press.