Dataset Information

Association of hypometabolism and amyloid levels in aging, normal subjects.

ABSTRACT: We evaluated the relationship of amyloid, seen on Pittsburgh compound B (PiB)-PET, and metabolism, seen on [(18)F]-fluorodeoxyglucose (FDG)-PET, in normal subjects to better understand pathogenesis and biomarker selection in presymptomatic subjects.Normal participants (aged 70-95 years; 600 with PiB-PET, FDG-PET, and MRI) were included. We performed a cross-sectional evaluation and subcategorized participants into amyloid-negative (<1.4), high-normal (1.4-1.5), positive (1.5-2.0), and markedly positive (>2.0) PiB standardized uptake value ratio groups representing different levels of amyloid brain load. Associations with metabolism were assessed in each group. Relationships with APOE ?4 carriage were evaluated.Hypometabolism in "Alzheimer disease (AD)-signature" regions was strongly associated with PiB load. Hypometabolism was greater with more positive PiB levels. Additional, more-diffuse cortical hypometabolism was also found to be associated with PiB, although less so. No hypermetabolism was seen in any subset. No significant incremental hypometabolism was seen in APOE-positive vs -negative subjects.Hypometabolism in PiB-positive, cognitively normal subjects in a population-based cohort occurs in AD-signature cortical regions and to a lesser extent in other cortical regions. It is more pronounced with higher amyloid load and supports a dose-dependent association. The effect of APOE ?4 carriage in this group of subjects does not appear to modify their hypometabolic "AD-like" neurodegeneration. Consideration of hypometabolism associated with amyloid load may aid trials of AD drug therapy.

SUBMITTER: Lowe VJ

PROVIDER: S-EPMC4105262 | biostudies-other | 2014 Jun

REPOSITORIES: biostudies-other

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Association of hypometabolism and amyloid levels in aging, normal subjects.

Lowe Val J VJ Weigand Stephen D SD Senjem Matthew L ML Vemuri Prashanthi P Jordan Lennon L Kantarci Kejal K Boeve Bradley B Jack Clifford R CR Knopman David D Petersen Ronald C RC

Neurology 20140502 22

<h4>Objective</h4>We evaluated the relationship of amyloid, seen on Pittsburgh compound B (PiB)-PET, and metabolism, seen on [(18)F]-fluorodeoxyglucose (FDG)-PET, in normal subjects to better understand pathogenesis and biomarker selection in presymptomatic subjects.<h4>Methods</h4>Normal participants (aged 70-95 years; 600 with PiB-PET, FDG-PET, and MRI) were included. We performed a cross-sectional evaluation and subcategorized participants into amyloid-negative (<1.4), high-normal (1.4-1.5), ...[more]

PMID: 24793183

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Project description: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.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.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 ?4 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).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.

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Association of hypometabolism and amyloid levels in aging, normal subjects.

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Association of hypometabolism and amyloid levels in aging, normal subjects.

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