Heterogeneity of PD-MCI in Candidates to Subthalamic Deep Brain Stimulation: Associated Cortical and Subcortical Modifications

Article type: Research Article

Authors: Devignes, Quentin^{a; 1} | Daoudi, Sami^{a; 1} | Viard, Romain^b | Lopes, Renaud^b | Betrouni, Nacim^a | Kuchcinski, Gregory^b | Rolland, Anne-Sophie^c | Moreau, Caroline^a | Defebvre, Luc^a | Bardinet, Eric^d | Bonnet, Marie^e | Brefel-Courbon, Christine^f | Delmaire, Christine^g | El Mountassir, Fouzia^h | Fluchère, Frédériqueⁱ | Fradet, Anne^j | Giordana, Caroline^k | Hainque, Elodie^l | Houvenaghel, Jean-François^m | Jarraya, Béchirⁿ | Klinger, Hélène^o | Maltête, David^p | Marques, Ana^q | Meyer, Mylène^r | Rascol, Olivier^s | Rouaud, Tiphaine^t | Tir, Melissa^u | Wirth, Thomas^{v; w} | Corvol, Jean-Christophe^l | Devos, David^{a; c} | Dujardin, Kathy^{a; *} | for the PREDISTIM working group

Affiliations: [a] Univ. Lille, Inserm, Lille Neurosciences and Cognition, CHU-Lille, Neurology and Movement Disorders department, NS-Park/F-CRIN, Lille, France | [b] Univ. Lille, CNRS, Inserm, US 41 – UMS 2014 – PLBS, CHU Lille, Lille Pasteur Institute, Lille, France | [c] Univ. Lille, Inserm, Lille Neurosciences and Cognition, CHU-Lille, Department of Medical Pharmacology, NS-Park/F-CRIN, Lille, France | [d] Institut du Cerveau (ICM), Centre de Neuro-Imagerie de Recherche (CENIR), UMR S 1127, CNRS UMR 7225, Sorbonne Université, Paris, France | [e] Centre Expert Parkinson, NS-Park/F-CRIN, Centre Mémoire de Ressources et de Recherche, IMNc, Hôpital Pellegrin, CHU de Bordeaux, France | [f] Service de Neurologie B8, Centre Expert Parkinson, NS-Park/F-CRIN, Hôpital Pierre Paul Riquet, CHU Purpan, Toulouse, France | [g] Department of Radiology, NS-Park/F-CRIN, Hôpital Fondation A de Rothschild, Paris, France | [h] Université Paris-Saclay, CEA, CNRS, Baobab, Neurospin, Gif-sur-Yvette, France and Institut du Cerveau (ICM), UMR S 1127, CNRS UMR 7225, Sorbonne Université, Paris, France | [i] Department of Neurology, NS-Park/F-CRIN, Assistance Publique - Hôpitaux de Marseille (APHM), Timone University Hospital and Institut de Neurosciences de la Timone, Marseille, France | [j] Neurology Department, NS-Park/F-CRIN, University Hospital of Poitiers and INSERM, University of Poitiers, Centre d’Investigation Clinique CIC 1402, Poitiers, France | [k] Department of Neurology, NS-Park/F-CRIN, Centre Hospitalier Universitaire de Nice, Nice, France | [l] Sorbonne Université, Paris Brain Institute – ICM, NS-Park/F-CRIN, Assistance publique Hôpitaux de Paris, Inserm, CRNS, Hôpital Pitié-Salpêtrière, Department of Neurology, Paris, France | [m] Department of Neurology, NS-PARK/F-CRIN, University Hospital of Rennes, Rennes, France | [n] Neuroscience Pole, NS-Park/F-CRIN, Hôpital Foch, Suresnes, University of Versailles Paris-Saclay, INSERM-CEA NeuroSpin, Saclay, France | [o] Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, NS-Park/F-CRIN, Lyon, France | [p] Department of Neurology, NS-Park/F-CRIN, Rouen University Hospital and University of Rouen, France; INSERM U1239, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan, France | [q] Université Clermont Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal, Clermont-Ferrand University Hospital, Neurology department, NS-Park/F-CRIN, Clermont-Ferrand, France | [r] Neurology department, NS-Park/F-CRIN, Central Hospital, CHRU-Nancy, Nancy, France | [s] Department of Clinical Pharmacology and Neuroscience, NS-Park/F-CRIN, Toulouse University Hospital, Toulouse, France | [t] Department of Neurology, Centre Expert Parkinson, NS-Park/F-CRIN, CHU Nantes, Nantes, France | [u] Department of Neurology, NS-PARK/FCRIN, Amiens University Hospital, Amiens, France | [v] Service de Neurologie, NS-Park/F-CRIN, Hôpitaux Universitaires de Strasbourg et Fédération de Médecine Translationnelle de Médecine de Strasbourg, Strasbourg, France | [w] Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France

Correspondence: [*] Correspondence to: Kathy Dujardin, PhD, Neurologie et pathologies du mouvement, Hôpital Salengro, CHU Lille, Rue Emile Laine, 59037 Lille Cedex, France. Tel.: +33 320 44 67 52; Fax: +33 320 44 66 80; E-mail: [email protected].

Note: [1] These authors share first authorship.

Abstract: Background:Parkinson’s disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. Objective:To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups. Methods:Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels. Results:320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes. Conclusion:Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia.

Keywords: Cortical thickness, dual syndrome hypothesis, radiomics, shape analysis, voxel-based morphometry

DOI: 10.3233/JPD-223232

Journal: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1507-1526, 2022