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J Cereb Blood Flow Metab. 2016 Dec;36(12):2058-2071. Epub 2016 Jun 14.

Modulation of glucose metabolism and metabolic connectivity by β-amyloid.

Author information

1
Biospective Inc., Montreal, Canada felix@biospective.com.
2
Biospective Inc., Montreal, Canada.
3
Montreal Neurological Institute, McGill University, Montreal, Canada.
4
McGill University, Montreal, Canada.

Abstract

Glucose hypometabolism in the pre-clinical stage of Alzheimer's disease (AD) has been primarily associated with the APOE ɛ4 genotype, rather than fibrillar β-amyloid. In contrast, aberrant patterns of metabolic connectivity are more strongly related to β-amyloid burden than APOE ɛ4 status. A major limitation of previous studies has been the dichotomous classification of subjects as amyloid-positive or amyloid-negative. Dichotomous treatment of a continuous variable, such as β-amyloid, potentially obscures the true relationship with metabolism and reduces the power to detect significant changes in connectivity. In the present work, we assessed alterations of glucose metabolism and metabolic connectivity as continuous function of β-amyloid burden using positron emission tomography scans from the Alzheimer's Disease Neuroimaging Initiative study. Modeling β-amyloid as a continuous variable resulted in better model fits and improved power compared to the dichotomous model. Using this continuous model, we found that both APOE ɛ4 genotype and β-amyloid burden are strongly associated with glucose hypometabolism at early stages of Alzheimer's disease. We also determined that the cumulative effects of β-amyloid deposition result in a particular pattern of altered metabolic connectivity, which is characterized by global, synchronized hypometabolism at early stages of the disease process, followed by regionally heterogeneous, progressive hypometabolism.

KEYWORDS:

Alzheimer’s disease; glucose metabolism; metabolic connectivity; positron emission tomography; β-amyloid

PMID:
27301477
PMCID:
PMC5363668
DOI:
10.1177/0271678X16654492
[Indexed for MEDLINE]
Free PMC Article

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