Dataset Information

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions.

ABSTRACT:

Objective

To investigate whether higher fasting serum glucose levels in cognitively normal, nondiabetic adults were associated with lower regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer disease (AD).

Methods

This is a cross-sectional study of 124 cognitively normal persons aged 64 ± 6 years with a first-degree family history of AD, including 61 APOE?4 noncarriers and 63 carriers. An automated brain mapping algorithm characterized and compared correlations between higher fasting serum glucose levels and lower [(18)F]-fluorodeoxyglucose-PET rCMRgl measurements.

Results

As predicted, higher fasting serum glucose levels were significantly correlated with lower rCMRgl and were confined to the vicinity of brain regions preferentially affected by AD. A similar pattern of regional correlations occurred in the APOE?4 noncarriers and carriers.

Conclusions

Higher fasting serum glucose levels in cognitively normal, nondiabetic adults may be associated with AD pathophysiology. Findings suggest that the risk imparted by higher serum glucose levels may be independent of APOE?4 status. This study raises additional questions about the role of the metabolic process in the predisposition to AD and supports the possibility of targeting these processes in presymptomatic AD trials.

SUBMITTER: Burns CM

PROVIDER: S-EPMC3662330 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions.

Burns Christine M CM Chen Kewei K Kaszniak Alfred W AW Lee Wendy W Alexander Gene E GE Bandy Daniel D Fleisher Adam S AS Caselli Richard J RJ Reiman Eric M EM

Neurology 20130327 17

<h4>Objective</h4>To investigate whether higher fasting serum glucose levels in cognitively normal, nondiabetic adults were associated with lower regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer disease (AD).<h4>Methods</h4>This is a cross-sectional study of 124 cognitively normal persons aged 64 ± 6 years with a first-degree family history of AD, including 61 APOEε4 noncarriers and 63 carriers. An automated brain mapping algorithm chara ...[more]

PMID: 23535495

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Project description:The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20).To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association.A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases.Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status.Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P <?.001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P <?.001) and lower Mini-Mental State Examination scores (-1.605; range, -3.095 to -0.114; P <?.0001). The Mini-Mental State Examination scores in the highest tertile of DDE were -1.753 points lower in the subpopulation carrying an APOE ?4 allele compared with those carrying an APOE ?3 allele (P interaction =?.04). Serum levels of DDE were highly correlated with brain levels of DDE (? = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein.Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ?4 allele may be more susceptible to the effects of DDE. Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. Identifying people who have elevated levels of DDE and carry an APOE ?4 allele may lead to early identification of some cases of AD.

Dataset Information

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions.

Objective

Methods

Results

Conclusions

Publications

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions.

Similar Datasets

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