Long-Term Cognitive Decline Related to the Motor Phenotype in Parkinson’s Disease

Article type: Research Article

Authors: Michels, Jennifer^{a; b} | van der Wurp, Hendrik^c | Kalbe, Elke^d | Rehberg, Sarah^d | Storch, Alexander^{e; f} | Linse, Katharina^e | Schneider, Christine^e | Gräber, Susanne^g | Berg, Daniela^{g; h} | Dams, Judithⁱ | Balzer-Geldsetzer, Monika^{c; i} | Hilker-Roggendorf, Rüdiger^j | Oberschmidt, Carola^j | Baudrexel, Simon^j | Witt, Karsten^k | Schmidt, Nele^h | Deuschl, Günther^h | Mollenhauer, Brit^{l; m} | Trenkwalder, Claudia^{l; m} | Liepelt-Scarfone, Inga^{g; s} | Spottke, Annikaⁿ | Roeske, Sandraⁿ | Wüllner, Ullrichⁿ | Wittchen, Hans-Ulrich^{o; p} | Riedel, Oliver^q | Kassubek, Jan^r | Dodel, Richard^{c; i} | Schulz, Jörg Bernhard^{a; b} | Costa, Ana Sofia^{a; b; 1} | Reetz, Kathrin^{a; b; 1; *}

Affiliations: [a] Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany | [b] JARA Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, Aachen, Germany | [c] Department of Geriatric Medicine, University Duisburg-Essen, Germany | [d] Medical Psychology, Neuropsychology and Gender Studies & Center for Neuropsychological Diagnostics and Intervention (CeNDI), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany | [e] Department of Neurology, University Hospital Augsburg, Augsburg, Germany | [f] Department of Neurology, University of Rostock, and German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Rostock, Germany | [g] German Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany | [h] Department of Neurology, Christian Albrecht University, Kiel, Germany | [i] Department of Neurology, Philipps University Marburg, Marburg, Germany | [j] Department of Neurology, J.W. Goethe University, Frankfurt/Main, Germany | [k] Department of Neurology, School of Medicine and Health Sciences - European Medical School, University Oldenburg and Research Center Neurosensory Science, Carl von Ossietzky University Oldenburg, Germany | [l] Paracelsus-Elena Clinic, Centre of Parkinsonism and Movement Disorders, Kassel, Germany | [m] Department of Neurology (BM) and Department of Neurosurgery (CT), University Medical Center Goettingen, Goettingen, Germany | [n] Department of Neurology, University Hospital Bonn, and German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany | [o] Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany | [p] Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität, München, Germany | [q] Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany | [r] Department of Neurology, University of Ulm, Ulm, Germany | [s] IB-Hochschule für Gesundheit und Soziales, Stuttgart, Germany

Correspondence: [*] Correspondence to: Prof. Dr. Kathrin Reetz, MD, Department of Neurology, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany. Tel.: +49 (0) 241 80 8960; Fax: +49 (0) 241 80 33 8960; E-mail: [email protected].

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

Abstract: Background:Parkinson’s disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. Objective:Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). Methods:Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M = 67.57; 67.4% males). We computed z-transformed composite scores for a priori defined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year follow-up data of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M = 66.10; 68.6% males). Results:Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients were present and we found differences for motor phenotypes in attention (β= –0.08, SE = 0.003, p < 0.006) and memory functions showing that PIGD-patients deteriorate per months by –0.006 compared to the ND-group (SE = 0.003, p = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. Conclusion:Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype.

Keywords: Cognitive decline, dementia, longitudinal, mild cognitive impairment, Parkinson’s disease, postural instability and gait disorder, progression, tremor-dominant

DOI: 10.3233/JPD-212787

Journal: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 905-916, 2022