Association between Longitudinal Increases in Serum Glucose and Metabolic Decline in Azheimer’s Disease-Related Brain Regions (P6.321)

OBJECTIVE: To investigate the association between longitudinal increases in fasting serum glucose levels and declines in cerebral metabolism in Alzheimer’s disease (AD) related brain regions. BACKGROUND: Cross-sectional positron emission tomography (PET) studies in cognitively unimpaired adults have found associations between indicators of insulin resistance and reduced regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by AD. In this study, we sought to characterize the association between longitudinal increases in serum glucose and rCMRgl declines in AD-affected regions. DESIGN/METHODS: Baseline, interim, and 4.4 ± 1.0-year follow-up fasting serum glucose and flourodeoxyglucose PET CMRgl were analyzed in 80 cognitively normal, non-diabetic, 61 ± 5 year-old persons with a first-degree history of AD, including 38 carriers and 42 non-carriers of the apolipoprotein E (APOE) e 4 allele. An automated brain-mapping algorithm was used to characterize associations between rCMRgl declines and fasting serum glucose increases. Longitudinal changes between fasting serum glucose levels and six pre-selected neuropsychological test measures of memory, attention and processing speed were also assessed with linear regression. RESULTS: Longitudinal increases in fasting serum glucose levels were associated with longitudinal CMRgl declines in the vicinity of brain regions preferentially affected by AD ( p < 0.05, corrected for multiple comparisons), and these associations were unrelated to presence or absence of the APOE e 4 allele. Longitudinal increases in fasting serum glucose were also associated with longitudinal a decline in a measure of visuospatial memory (Rey-Osterrieth Complex Figure Test, Delayed Recall; p < 0.05, corrected for multiple comparisons). CONCLUSIONS: Longitudinal increases in fasting serum glucose are associated with longitudinal CMRgl declines in AD-affected brain regions and memory. Additional studies are needed to clarify and confirm these relationships and set the stage for evaluating glucose-regulating agents in preclinical AD trials. Disclosure: Dr. Burns has nothing to disclose. Dr. Kaszniak has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Bandy has nothing to disclose. Dr. Caselli has received personal compensation in an editorial capacity for Clinical Neurology News. Dr. Reiman has received personal compensation for activities with AstraZeneca, Bayer Pharmaceuticals Corp., Esai Inc., Eli Lilly & Co., Novartis, Siemens, Takeda, AstraZeneca, and Avid Pharmaceuticals. Dr. Reiman has received research support from AstraZeneca and Avid Pharmaceuticals.