Deep brain stimulation and cognition in managing motor fluctuations in Parkinson's disease

Parkinson’s disease (PD) is one of the fastest growing neurodegenerative disorders worldwide. Motor symptoms are initially managed with levodopa and adjunctive oral therapy, namely catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs), or monoamine oxidase B inhibitors (MAOB-Is). Part I of this thesis presents a systematic review with network meta-analysis of randomized controlled trials comparing the efficacy and safety of COMT-Is, DRAs and MAOB-Is as adjunctive oral therapy to levodopa in PD patients experiencing motor fluctuations. All adjunctive drug classes improved motor symptoms, activities of daily living, and quality of life, but DRAs, particularly pramipexole immediate release, were associated with the largest improvements. In Part II cognitive outcomes following subthalamic nucleus deep brain stimulation (STN DBS) in PD patients were examined. Overall, STN DBS appears to be a cognitively safe intervention, with cognitive outcomes comparable to continuous intrajejunal levodopa infusion and only a transient moderate decline in verbal fluency compared to best medical treatment (BMT). Furthermore, STN DBS induces a clinically meaningful motor improvement in PD patients with cognitive impairment, but the improvement may be smaller than in patients who are not cognitively affected. Lastly, smaller volume of the nucleus basalis of Meynert was associated with Parkinson’s disease dementia (PDD) at baseline, but not with cognitive decline six months after STN DBS. Part III aimed to facilitate future research in cognitively impaired PD patients by introducing the DBS-MODE trial, a randomized controlled study comparing DBS with BMT in PDD, and by providing practical recommendations for obtaining informed consent in PD patients with cognitive impairment.