Antonio Canosa1, Marco Pagani1, Angelina Cistaro1, Anna Montuschi1, Barbara Iazzolino1, Piercarlo Fania1, Stefania Cammarosano1, Antonio Ilardi1, Cristina Moglia1, Andrea Calvo1, Adriano Chiò2. 1. From the ALS Center (A. Canosa, A.M., B.I., S.C., A.I., C.M., A. Calvo, A. Chiò), "Rita Levi Montalcini" Department of Neuroscience, University of Turin; Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health (A. Canosa), University of Genoa; Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro, A. Chiò), C.N.R., Rome, Italy; Department of Nuclear Medicine (M.P.), Karolinska Hospital, Stockholm, Sweden; Positron Emission Tomography Centre IRMET S.p.A. (A. Cistaro, P.F.), EuroMedic International, Turin; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino (A. Calvo, A. Chiò), Turin; and the Neuroscience Institute of Turin (NIT) (A. Calvo, A. Chiò), Italy. 2. From the ALS Center (A. Canosa, A.M., B.I., S.C., A.I., C.M., A. Calvo, A. Chiò), "Rita Levi Montalcini" Department of Neuroscience, University of Turin; Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health (A. Canosa), University of Genoa; Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro, A. Chiò), C.N.R., Rome, Italy; Department of Nuclear Medicine (M.P.), Karolinska Hospital, Stockholm, Sweden; Positron Emission Tomography Centre IRMET S.p.A. (A. Cistaro, P.F.), EuroMedic International, Turin; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino (A. Calvo, A. Chiò), Turin; and the Neuroscience Institute of Turin (NIT) (A. Calvo, A. Chiò), Italy. achio@usa.net.
Abstract
OBJECTIVE: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-d-glucose-PET (18F-FDG-PET). METHODS: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent brain 18F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n = 94), full-blown frontotemporal dementia (ALS-FTD; n = 20), executive or nonexecutive cognitive impairment not fulfilling FTD criteria (ALS-Ci; n = 37), prevalent behavioral changes (n = 9), or nonclassifiable impairment (n = 10) according to neuropsychological testing. Group comparisons of 18F-FDG-PET pattern were carried out among the cognitive subgroups. RESULTS: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex, being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the larger the size of the cluster and the statistical significance of 18F-FDG uptake differences. CONCLUSIONS: This study demonstrated in a large cohort of patients with ALS a continuum of frontal lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients with intermediate cognitive impairment display a characteristic metabolic pattern. Since 18F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases, it might be helpful to investigate in ALS its association with neuropsychological testing along the disease course to disclose the early metabolic signature of possible cognitive impairment.
OBJECTIVE: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-d-glucose-PET (18F-FDG-PET). METHODS: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent brain 18F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n = 94), full-blown frontotemporal dementia (ALS-FTD; n = 20), executive or nonexecutive cognitive impairment not fulfilling FTD criteria (ALS-Ci; n = 37), prevalent behavioral changes (n = 9), or nonclassifiable impairment (n = 10) according to neuropsychological testing. Group comparisons of 18F-FDG-PET pattern were carried out among the cognitive subgroups. RESULTS: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex, being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the larger the size of the cluster and the statistical significance of 18F-FDG uptake differences. CONCLUSIONS: This study demonstrated in a large cohort of patients with ALS a continuum of frontal lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients with intermediate cognitive impairment display a characteristic metabolic pattern. Since 18F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases, it might be helpful to investigate in ALS its association with neuropsychological testing along the disease course to disclose the early metabolic signature of possible cognitive impairment.
Authors: Stefanie M A Willekens; Donatienne Van Weehaeghe; Philip Van Damme; Koen Van Laere Journal: Eur J Nucl Med Mol Imaging Date: 2016-12-08 Impact factor: 9.236
Authors: Jordi A Matías-Guiu; Vanesa Pytel; María Nieves Cabrera-Martín; Lucía Galán; María Valles-Salgado; Antonio Guerrero; Teresa Moreno-Ramos; Jorge Matías-Guiu; José Luis Carreras Journal: Eur J Nucl Med Mol Imaging Date: 2016-06-04 Impact factor: 9.236
Authors: Colin J Mahoney; Rebekah M Ahmed; William Huynh; Sicong Tu; Jonathan D Rohrer; Richard S Bedlack; Orla Hardiman; Matthew C Kiernan Journal: CNS Drugs Date: 2021-05-15 Impact factor: 5.749
Authors: Christopher M Henstridge; Dimitrios I Sideris; Emily Carroll; Sanziana Rotariu; Sally Salomonsson; Makis Tzioras; Chris-Anne McKenzie; Colin Smith; Christine A F von Arnim; Albert C Ludolph; Dorothée Lulé; Danielle Leighton; Jon Warner; Elaine Cleary; Judith Newton; Robert Swingler; Siddharthan Chandran; Thomas H Gillingwater; Sharon Abrahams; Tara L Spires-Jones Journal: Acta Neuropathol Date: 2017-12-22 Impact factor: 17.088