title: Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation.
abstract: Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using (11)C-Pittsburgh compound B ((11)C-PiB) and brain hypometabolism measured using (18)F-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 (18)F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for (11)C-PiB retention ratio and (18)F-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), (18)F-FDG hypometabolism ((18)F-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 (18)F-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 (18)F-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 (11)C-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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Cha
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.forename: Yonas E
authors.initials: YE
authors.lastname: Geda
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging; D000682:Amyloid / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003071:Cognition; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D016017:Odds Ratio; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D000682:Amyloid; D053327:Apolipoprotein E4; D002250:Carbon Radioisotopes; D019788:Fluorodeoxyglucose F18; D006442:Glycated Hemoglobin; D007328:Insulin; D019275:Radiopharmaceuticals; C517652:hemoglobin A1c protein, human
keywords: 11C-PiB PET imaging; 18F-FDG PET imaging; amyloid accumulation; cerebral glucose metabolism; diabetes; hemoglobin A1c