Modulation of glucose metabolism and metabolic connectivity by beta-amyloid

作者：Carbonell Felix^*; Zijdenbos Alex P; McLaren Donald G; Iturria Medina Yasser; Bedell Barry J

来源：Journal of Cerebral Blood Flow and Metabolism, 2016, 36(12): 2058-2071.

DOI：10.1177/0271678X16654492

• Alzheimer's disease
• beta-amyloid
• glucose metabolism
• metabolic connectivity
• positron emission tomography

Glucose hypometabolism in the pre-clinical stage of Alzheimer's disease (AD) has been primarily associated with the APOE epsilon 4 genotype, rather than fibrillar beta-amyloid. In contrast, aberrant patterns of metabolic connectivity are more strongly related to beta-amyloid burden than APOE e4 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 beta-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 beta-amyloid burden using positron emission tomography scans from the Alzheimer's Disease Neuroimaging Initiative study. Modeling beta-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 e4 genotype and beta-amyloid burden are strongly associated with glucose hypometabolism at early stages of Alzheimer's disease. We also determined that the cumulative effects of beta-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.

• 出版日期2016-12