PT  - JOURNAL ARTICLE
AU  - Rosebud O. Roberts
AU  - David S. Knopman
AU  - Ruth H. Cha
AU  - Michelle M. Mielke
AU  - V. Shane Pankratz
AU  - Bradley F. Boeve
AU  - Kejal Kantarci
AU  - Yonas E. Geda
AU  - Clifford R. Jack, Jr.
AU  - Ronald C. Petersen
AU  - Val J. Lowe
TI  - Diabetes and Elevated Hemoglobin A1c Levels Are Associated with Brain Hypometabolism but Not Amyloid Accumulation
AID  - 10.2967/jnumed.113.132647
DP  - 2014 May 01
TA  - Journal of Nuclear Medicine
PG  - 759--764
VI  - 55
IP  - 5
4099  - http://jnm.snmjournals.org/content/55/5/759.short
4100  - http://jnm.snmjournals.org/content/55/5/759.full
SO  - J Nucl Med2014 May 01; 55
AB  - Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using 11C-Pittsburgh compound B (11C-PiB) and brain hypometabolism measured using 18F-FDG PET. Methods: We studied a sample of nondemented participants from the population-based Mayo Clinic Study of Aging. All subjects underwent MR imaging, amyloid PET, and 18F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for 11C-PiB retention ratio and 18F-FDG ratio were measured. Diabetes was assessed from the Rochester Epidemiology Project medical records linkage system. Results: Among 749 participants (median age, 79.0 y; 56.5% men, 81.0% cognitively normal; 20.6% diabetic individuals), 18F-FDG hypometabolism (18F-FDG ratio < 1.31) in the AD signature meta-ROI was more common in diabetic individuals (48.1%) than in nondiabetic individuals (28.9%; P < 0.001). The median 18F-FDG ratio was lower in diabetic individuals than in nondiabetic individuals in the AD signature meta-ROI (1.32 vs. 1.40, P < 0.001) and in the angular (1.40 vs. 1.48, P < 0.001) and posterior cingulate gyri ROIs (1.63 vs. 1.72, P < 0.001). The odds ratio (OR) for abnormal AD signature 18F-FDG hypometabolism was elevated (2.28; 95% confidence interval [CI], 1.56–3.33) in diabetic individuals versus nondiabetic individuals after adjustment for age, sex, and education and after additional adjustment for apolipoprotein ε4 allele, glycemic level, and cognitive status (OR, 1.69; 95% CI, 1.10–2.60). However, the AD signature 11C-PiB retention ratio was similar in diabetic individuals versus nondiabetic individuals (OR, 1.03; 95% CI, 0.71–1.51; P = 0.87). In post hoc analyses in nondiabetic individuals, a 1% increase in hemoglobin A1c was associated with greater AD signature hypometabolism in cognitively normal subjects (OR, 1.93; 95% CI, 1.03–3.62; P = 0.04) and in the total cohort (OR 1.59; 95% CI, 0.92–2.75; P = 0.10). Conclusion: Diabetes and poor glycemic control in nondiabetic individuals may enhance glucose hypometabolism in AD signature regions. These factors should be investigated in longitudinal studies for their role in detecting onset of symptoms in AD.