Parkinson’s disease and in its prodromal stages with a focus on retrograde procedural memory

Today, more than two centuries after Dr. James Parkinson’s initial description of Parkinson’s disease (PD), our point of view has been broadened beyond the perception of PD as a motor disorder.
Nowadays, we recognise a multitude of non-motor symptoms such as cognitive impairment in PD and its substantial impact on quality of life.
Through this doctoral dissertation, we aim to acquire novel insights into the cognition of people with PD and in its prodromal stages, with a focus on retrograde procedural memory. As an initial step, we focused on the development of the CUPRO (CUbe drawing PROcedure), an extended evaluation system of the Cube Copying Task, suggestive for assessing retrograde procedural memory. We applied the CUPRO evaluation system to the Luxembourg Parkinson’s Study cohort and compared the performances of people with PD to age- and sex-matched control subjects. We observed significantly lower CUPRO scores in people with PD, suggestive of impaired functioning of retrograde procedural memory in PD. In a second step, we compared cognition, with a focus on the CUPRO performance in people with PD and Freezing of Gait (FOG), a de-automatization disorder of walking, to a counter group of PD without FOG. Besides significantly lower global cognition and mental flexibility, the deficit of retrograde procedural memory was significantly more prominent in PD with FOG compared to the matched counter group. Lastly, we focused on the pre-motor stages of PD, the prodromal PD (P-PD). We investigated non-motor symptoms, focusing on cognition in people at high risk of developing PD, presenting risk factors such as probable Restless-Eye-Movement (REM) Sleep Behaviour Disorder (RBD) and olfactory dysfunction. In this P-PD group, we described early global cognitive, executive, and visuo-constructive function deficits compared to the matched control group. No significant differences have been observed for the retrograde procedural memory at the P-PD stages.
The thesis summarizes the present status of research in the field of PD and offers a thorough exploration of the cognitive changes spanning from the prodromal to the already advanced disease stage. All in all, our primary goal was to gain a deeper understanding of the often invisible symptoms of PD, the cognitive impairment and to, in the future, reduce the burden for people with PD and contribute to the early recognition of PD, helping to get a better prognosis, as soon as disease-modifying treatments are available.