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Metabolic brain changes across different levels of cognitive impairment in ALS: a 18F-FDG-PET study
  1. Antonio Canosa1,2,
  2. Cristina Moglia1,2,
  3. Umberto Manera1,
  4. Rosario Vasta1,
  5. Maria Claudia Torrieri1,
  6. Vincenzo Arena3,
  7. Fabrizio D'Ovidio1,
  8. Francesca Palumbo1,
  9. Jean Pierre Zucchetti1,
  10. Barbara Iazzolino1,
  11. Laura Peotta1,
  12. Andrea Calvo1,2,4,
  13. Marco Pagani5,6,
  14. Adriano Chiò1,2,4,5
  1. 1 "Rita Levi Montalcini" Department of Neuroscience, University of Turin, ALS Centre, Turin, Italy
  2. 2 SC Neurologia 1U, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
  3. 3 Positron Emission Tomography Centre AFFIDEA-IRMET S.p.A, Turin, Italy
  4. 4 Neuroscience Institute of Turin (NIT), Turin, Italy
  5. 5 Institute of Cognitive Sciences and Technologies, C.N.R, Rome, Italy
  6. 6 Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to Antonio Canosa, "Rita Levi Montalcini" Department of Neuroscience, ALS Centre, University of Turin, Turin, 10126, Italy; antonio.canosa{at}


Objective To identify the metabolic changes related to the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) imaging.

Methods 274 ALS patients underwent neuropsychological assessment and brain 18F-FDG-PET at diagnosis. According to the criteria published in 2017, cognitive status was classified as ALS with normal cognition (ALS-Cn, n=132), ALS with behavioural impairment (ALS-Bi, n=66), ALS with cognitive impairment (ALS-Ci, n=30), ALS with cognitive and behavioural impairment (ALS-Cbi, n=26), ALS with frontotemporal dementia (ALS–FTD, n=20). We compared each group displaying some degree of cognitive and/or behavioural impairment to ALS-Cn patients, including age at PET, sex and ALS Functional Rating Scale-Revised as covariates.

Results We identified frontal lobe relative hypometabolism in cognitively impaired patients that resulted more extensive and significant across the continuum from ALS-Ci, through ALS-Cbi, to ALS–FTD. ALS–FTD patients also showed cerebellar relative hypermetabolism. ALS-Bi patients did not show any difference compared with ALS-Cn.

Conclusions These data support the concept that patients with cognitive impairment have a more widespread neurodegenerative process compared with patients with a pure motor disease: the more severe the cognitive impairment, the more diffuse the metabolic changes. Otherwise, metabolic changes related to pure behavioural impairment need further characterisation.

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  • MP and ACh contributed equally.

  • Contributors Study concept and design: ACan, MP, ACh. Acquisition of data: ACan, CM, UM, RV, MCT, VA, FP, JPZ, BI, LP, ACal. Analysis and interpretation of data: ACan, CM, FD’O, ACal, MP, ACh. Drafting of the manuscript: ACan, MP, ACh. Critical revision of the manuscript for important intellectual content: ACan, CM, UM, RV, MCT, VA, FD’O, FP, JPZ, BI, LP, ACal, MP, ACh. Administrative, technical and material support: CM, UM, RV, MCT, VA, FP, JPZ, BI, LP. Obtained funding: MP, ACh. Study supervision: ACan, ACal, MP, ACh.

  • Funding This work was in part supported by a grant from the Thierry Latran Foundation (INSPIRED project), the Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata, grant RF-2016-02362405), the European Commission’s Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867), the Joint Programme: Neurodegenerative Disease Research (Strength, ALS-Care and Brain-Mend projects), granted by the Italian Ministry of Education, University and Research and the Progetti di Rilevante Interesse Nazionale (PRIN) 2017 granted by the Italian Ministry of Education, University and Research (grant 2017SNW5MB). This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Italy.

  • Competing interests ACan, CM, UM, RV, MCT, VA, FD’O, FP, JPZ, BI, LP and MP: no disclosures. ACal has received a research grant from Cytokinetics. ACh serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen and Cytokinetics, and has received a research grant from Italfarmaco. The sponsor organisations had no role in data collection and analysis and did not participate to writing and approving the manuscript. The information reported in the manuscript has never been reported elsewhere.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the ethical committee ‘Comitato Etico Interaziendale AziendaOspedaliero-Universitaria Città della Salute e della Scienza di Torino’. All of the patients signed written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement The data are available to interested researchers on request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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