title: Longitudinal brain metabolic changes from amnestic mild cognitive impairment to Alzheimer's disease.
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.
authors.affiliation: Inserm-EPHE-Université de Caen/Basse-Normandie, Unité U923, GIP Cyceron, CHU Côte de Nacre, Caen, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Fouquet
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desgranges
authors.forename: Brigitte
authors.initials: B
authors.lastname: Landeau
authors.forename: Edouard
authors.initials: E
authors.lastname: Duchesnay
authors.forename: Florence
authors.initials: F
authors.lastname: Mézenge
authors.forename: Vincent
authors.initials: V
authors.lastname: de la Sayette
authors.forename: Fausto
authors.initials: F
authors.lastname: Viader
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Baron
authors.forename: Francis
authors.initials: F
authors.lastname: Eustache
authors.forename: Gaël
authors.initials: G
authors.lastname: Chételat
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D000647:Amnesia / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D019788:Fluorodeoxyglucose F18