Long-Term Cognitive Decline Related to the Motor Phenotype in Parkinson’s Disease
Jennifer Michels, Hendrik van der Wurp, Elke Kalbe, Sarah Rehberg, Alexander Storch, Katharina Linse, Christine Schneider, Susanne Gräber, Daniela Berg, Judith Dams, Monika Balzer-Geldsetzer, Rüdiger Hilker-Roggendorf, Carola Oberschmidt, Simon Baudrexel, Karsten Witt, Nele Schmidt, Günther Deuschl, Brit Mollenhauer, Claudia Trenkwalder, Inga Liepelt-Scarfone, Annika Spottke, Sandra Roeske, Ullrich Wüllner, Hans-Ulrich Wittchen, Oliver Riedel, Jan Kassubek, Richard Dodel, Jörg Bernhard Schulz, Ana Sofia Costa, Kathrin Reetz
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.