Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer’s Disease and Frontotemporal Dementia: An Extended Case Series

Article type: Research Article

Authors: Moodley, Kuven K.^{a; 1} | Perani, Daniela^{b; 1} | Minati, Ludovico^{a; c} | Anthony Della Rosa, Pasquale^d | Pennycook, Frank^e | Dickson, John C.^f | Barnes, Anna^f | Elisa Contarino, Valeria^g | Michopoulou, Sofia^f | D’Incerti, Ludovico^g | Good, Catriona^h | Fallanca, Federico^b | Giovanna Vanoli, Emilia^b | Ell, Peter J.^f | Chan, Dennis^{a; *}

Affiliations: [a] Brighton and Sussex Medical School, Falmer, UK | [b] Vita-Salute San Raffaele University, Nuclear Medicine Unit San Raffaele Hospital, Division of Neuroscience IRCCS San Raffaele, Milano, Italy | [c] Scientific Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy | [d] Institute of Molecular Bio-imaging and Physiology, National Research Council, Milano, Italy | [e] OpenUniversity, Milton Keynes, UK | [f] Institute of Nuclear Medicine, University College London, London, UK | [g] Neuroradiology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy | [h] Hurstwood Park Neurosciences Centre, West Sussex, UK

Correspondence: [*] Correspondence to:Dr. Dennis Chan, Herchel Smith Buildingfor Brain and Mind Sciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0SZ, UK. Tel.: +44 1223 760696; Fax: +44 1223 336581; E-mail: [email protected]

Note: [1] These authors contributed equally to this work.

Abstract: Background: Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. Objectives: The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. Method: PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen’s kappa. Results: Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0–0.25 for PCA to 0.29–0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. Conclusion: The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practice

Keywords: Alzheimer’s disease, atrophy, frontotemporal dementia, hypometabolism, NEUROSTAT, simultaneous PET-MRI, statistical parametric mapping, visual rating

DOI: 10.3233/JAD-150151

Journal: Journal of Alzheimer's Disease, vol. 46, no. 3, pp. 639-653, 2015