M Gersel Stokholm1, A Iranzo2,3,4, K Østergaard5, M Serradell2,4, M Otto6, K Bacher Svendsen5, A Garrido3,7, D Vilas3,7, T D Fedorova1, J Santamaria2,3,4, A Møller1, C Gaig2,3,4, K Hiraoka8, D J Brooks1,9, N Okamura10, P Borghammer1, E Tolosa3,7, N Pavese1,9. 1. Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark. 2. Department of Neurology, Hospital Clínic de Barcelona, Barcelona. 3. Centro de Investigación Biomédica en Red sobre Enfermedades eurodegenerativas (CIBERNED) Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia. 4. Multidisciplinary Sleep Unit, Hospital Clinic, Barcelona, Spain. 5. Department of Neurology, Aarhus University Hospital, Aarhus. 6. Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark. 7. Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Catalonia, Spain. 8. Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. 9. Division of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. 10. Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Abstract
BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.
BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.
Authors: Mitchell G Miglis; Charles H Adler; Elena Antelmi; Dario Arnaldi; Luca Baldelli; Bradley F Boeve; Matteo Cesari; Irene Dall'Antonia; Nico J Diederich; Kathrin Doppler; Petr Dušek; Raffaele Ferri; Jean-François Gagnon; Ziv Gan-Or; Wiebke Hermann; Birgit Högl; Michele T Hu; Alex Iranzo; Annette Janzen; Anastasia Kuzkina; Jee-Young Lee; Klaus L Leenders; Simon J G Lewis; Claudio Liguori; Jun Liu; Christine Lo; Kaylena A Ehgoetz Martens; Jiri Nepozitek; Giuseppe Plazzi; Federica Provini; Monica Puligheddu; Michal Rolinski; Jan Rusz; Ambra Stefani; Rebekah L S Summers; Dallah Yoo; Jennifer Zitser; Wolfgang H Oertel Journal: Lancet Neurol Date: 2021-08 Impact factor: 44.182