Longitudinal brain metabolic changes from amnestic Mild Cognitive Impairment to Alzheimer's disease

Inserm-EPHE-Université de Caen/Basse-Normandie, Unité U923, GIP Cyceron, CHU Côte de Nacre, Caen, France.
Brain (Impact Factor: 10.23). 06/2009; 132(Pt 8):2058-67. DOI: 10.1093/brain/awp132
Source: PubMed

ABSTRACT A sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential monitoring marker, in patients with amnestic mild cognitive impairment, according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen amnestic mild cognitive impairment patients underwent magnetic resonance imaging and 18FDG-positron emission tomography scans both at inclusion and 18 months later. Baseline and follow-up positron emission tomography data were corrected for partial volume effects and spatially normalized using magnetic resonance imaging data, scaled to the vermis and compared using SPM2. 'PET-PAC' maps reflecting metabolic per cent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than non-converters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-positron emission tomography for monitoring early Alzheimer's disease progression.

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    • "Similarly, the IWG criteria for prodromal AD require the positivity of biomarkers, in association with the presence of hippocampal-type memory dysfunction (Dubois et al., 2014). [ 18 F]FDG-PET has been recognized as a crucial diagnostic marker in dementia since the early disease phases, predicting the possible progression to AD in MCI subjects (Anchisi et al., 2005; Chételat et al., 2005; Mosconi, 2005; Mosconi et al., 2008; Fouquet et al., 2009; Patterson II et al., 2010; Brück et al., 2013; Dukart et al., 2013; Hatashita & Yamasaki, 2013; Prestia et al., 2013), and allowing the exclusion of AD pathology (Silverman et al., 2008; Ossenkoppele et al., 2013). The typical AD metabolic pattern was shown even years before the disease onset, as proven in dominantly inherited AD (Bateman et al., 2012) and in familial sporadic cases (Mosconi et al., 2014). "
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