title: Brain metabolic maps in Mild Cognitive Impairment predict heterogeneity of progression to dementia.
abstract: [(18)F]FDG-PET imaging has been recognized as a crucial diagnostic marker in Mild Cognitive Impairment (MCI), supporting the presence or the exclusion of Alzheimer's Disease (AD) pathology. A clinical heterogeneity, however, underlies MCI definition. In this study, we aimed to evaluate the predictive role of single-subject voxel-based maps of [(18)F]FDG distribution generated through statistical parametric mapping (SPM) in the progression to different dementia subtypes in a sample of 45 MCI. Their scans were compared to a large normal reference dataset developed and validated for comparison at single-subject level. Additionally, Aβ42 and Tau CSF values were available in 34 MCI subjects. Clinical follow-up (mean 28.5 ± 7.8 months) assessed subsequent progression to AD or non-AD dementias. The SPM analysis showed: 1) normal brain metabolism in 14 MCI cases, none of them progressing to dementia; 2) the typical temporo-parietal pattern suggestive for prodromal AD in 15 cases, 11 of them progressing to AD; 3) brain hypometabolism suggestive of frontotemporal lobar degeneration (FTLD) subtypes in 7 and dementia with Lewy bodies (DLB) in 2 subjects (all fulfilled FTLD or DLB clinical criteria at follow-up); and 4) 7 MCI cases showed a selective unilateral or bilateral temporo-medial hypometabolism without the typical AD pattern, and they all remained stable. In our sample, objective voxel-based analysis of [(18)F]FDG-PET scans showed high predictive prognostic value, by identifying either normal brain metabolism or hypometabolic patterns suggestive of different underlying pathologies, as confirmed by progression at follow-up. These data support the potential usefulness of this SPM [(18)F]FDG PET analysis in the early dementia diagnosis and for improving subject selection in clinical trials based on MCI definition.
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy ; Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy ; Clinical Neuroscience Department, Neurorehabilitation Unit, San Raffaele Hospital, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerami
authors.affiliation: Istituto di Bioimmagini e Fisiologia Molecolare C.N.R., Segrate, Italy.
authors.forename: Pasquale Anthony
authors.initials: PA
authors.lastname: Della Rosa
authors.affiliation: Department of Neurology, San Raffaele Hospital, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magnani
authors.affiliation: Department of Neurology, San Raffaele Hospital, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Santangelo
authors.affiliation: Clinical Neuroscience Department, Neurorehabilitation Unit, San Raffaele Hospital, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.affiliation: Istituto Universitario degli Studi Superiori, Pavia, Italy.
authors.forename: Stefano F
authors.initials: SF
authors.lastname: Cappa
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy ; Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy ; Istituto di Bioimmagini e Fisiologia Molecolare C.N.R., Segrate, Italy ; Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Perani
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging*; D003704:Dementia / Q000000981:diagnostic imaging*; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011857:Radiographic Image Interpretation, Computer-Assisted / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: Alzheimer's disease; Dementia diagnosis; Mild Cognitive Impairment; PET imaging; [18F]FDG