Effects of Brain Amyloid Deposition and Reduced Glucose Metabolism on the Default Mode of Brain Function in Normal Aging

Abstract

Brain ␤-amyloid (A␤) deposition during normal aging is highlighted as an initial pathogenetic event in the development of Alzheimer's disease. Many recent brain imaging studies have focused on areas deactivated during cognitive tasks [the default mode network (DMN), i.e., medial frontal gyrus/anterior cingulate cortex and precuneus/posterior cingulate cortex], where the strength of functional coordination was more or less affected by cerebral A␤ deposits. In the present positron emission tomography study, to investigate whether regional glucose metabolic alterations and A␤ deposits seen in nondemented elderly human subjects (n ϭ 22) are of pathophysiological importance in changes of brain hemodynamic coordination in DMN during normal aging, we measured cerebral glucose metabolism with [18 F]FDG, A␤ deposits with [ 11 C]PIB, and regional cerebral blood flow during control and working memory tasks by H 2 15 O on the same day. Data were analyzed using both region of interest and statistical parametric mapping. Our results indicated that the amount of A␤ deposits was negatively correlated with hemodynamic similarity between medial frontal and medial posterior regions, and the lower similarity was associated with poorer working memory performance. In contrast, brain glucose metabolism was not related to this medial hemodynamic similarity. These findings suggest that traceable A␤ deposition, but not glucose hypometabolism, in the brain plays an important role in occurrence of neuronal discoordination in DMN along with poor working memory in healthy elderly people.

Cortical and Subcortical Cerebrovascular Resistance Index in Mild Cognitive Impairment and Alzheimer's Disease

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Enzyme-Modified Carbon-Fiber Microelectrode for the Quantification of Dynamic Fluctuations of Nonelectroactive Analytes Using Fast-Scan Cyclic Voltammetry

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Antioxidant peroxiredoxin 6 protein rescues toxicity due to oxidative stress and cellular hypoxia in vitro, and attenuates prion-related pathology in vivo

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