. Effects of brain amyloid deposition and reduced glucose metabolism on the default mode of brain function in normal aging. J Neurosci. 2011 Aug 3;31(31):11193-9. PubMed.


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  1. Kikuchi and colleagues reported a study of healthy normal individuals with an average age of 68 years. They evaluated the integrity of the brain’s default mode network (DMN), a site of early changes in AD, using oxygen-15 PET, and tested whether DMN disruption was related to memory performance, amyloid-β deposition, and glucose metabolism. Confirming previous studies (Sperling et al., 2009; Hedden et al., 2009; Sheline et al., 2010), they found that amyloid deposition was associated with DMN disruption in a deposit-dependent manner, but went on to demonstrate that the disruption was correlated with worse working memory performance.

    Given previous work (e.g., Dzrezga et al., 2011 and Cohen et al., 2009), one might expect Aβ-related brain network abnormalities to be associated with abnormal glucose metabolism in preclinical AD. However, in this study, fluorodeoxyglucose (FDG) metabolism was not related to memory task performance or to disruption of most DMN areas. The authors suggest that FDG hypometabolism may not be apparent in the DMN because of its greater dependence on aerobic glycolysis versus oxidative metabolism (Vlassenko et al., 2010), although they did find a smaller region of the DMN that was hypometabolic, suggesting some metabolic heterogeneity in the DMN.

    Since we know that FDG hypometabolism does arise as preclinical AD progresses to symptomatic phases, the challenge we face is to discover the timing and conditions under which this occurs. ApoE genotype, which was not evaluated in this study, may have an important role, and it is likely that future studies will require larger samples and control for the presence of brain volume loss. Research efforts are increasingly focused on detecting AD-related pathophysiology before clinical impairment is established. The Kikuchi et al. paper is one of several recent reports that lend support to the possibility of detecting AD at an earlier stage, in order to offer a possibly more timely treatment.


    . Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. J Neurosci. 2009 Oct 7;29(40):12686-94. PubMed.

    . Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron. 2009 Jul 30;63(2):178-88. PubMed.

    . Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden. Brain. 2011 Jun;134(Pt 6):1635-46. PubMed.

    . Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol Psychiatry. 2010 Mar 15;67(6):584-7. PubMed.

    . Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve. J Neurosci. 2009 Nov 25;29(47):14770-8. PubMed.

    . Spatial correlation between brain aerobic glycolysis and amyloid-β (Aβ ) deposition. Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17763-7. PubMed.

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