Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation - PubMed (original) (raw)

Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation

Rosebud O Roberts et al. J Nucl Med. 2014 May.

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).

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.

Keywords: 11C-PiB PET imaging; 18F-FDG PET imaging; amyloid accumulation; cerebral glucose metabolism; diabetes; hemoglobin A1c.

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Conflict of interest statement

Potential Conflicts of Interest

None.

Figures

FIGURE 1

Box plots for FDG and PiB retention ratio in AD signature regions by diabetes mellitus (DM) in cognitively normal and MCI subjects. Women (filled circles) and men (open circles).

FIGURE 2

Box plots of FDG ratio in AD signature regions in the total sample by diabetes (DM) status stratified by age (A: 70_–_79 years, B: 80 – 89 years), sex (C: women, D: men), and apolipoprotein ε4 allele (E: ε4 carrier, F: ε4 non-carrier). Women (filled circle), men (open circles).

FIGURE 3

FDG scans for participants without diabetes (A, cognitively normal; B, MCI) and with diabetes (C and D; both with MCI). Each image set represents 3-D SSP regional hypometabolism normalized to age appropriate normal subjects and displayed as a Z-score; upper boundary as 7.0 (red) and the lower boundary as 0.0 (black). A Z-score of 1.5 (medium blue) or greater would be considered significant.

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Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation - PubMed (original) (raw)