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Background A high percentage of dopaminergic axons are already lost at the time of diagnosis, current studies on neuroprotective agents focus mainly on the early stages of Parkinson’s disease (PD). Nevertheless, PD progresses slowly during the first years, making clinical trials challenging. The final phase of the disease, however, is characterized by a rapid deterioration with clinical milestones marking the transition. Objective To investigate whether PD is associated with increased neurodegeneration in the late stage rather than a functional or age-dependent deterioration. Methods Neurodegeneration was quantified in n = 118 patients with PD using serum neurofilament light chain (sNfL) as a biomarker. Late-stage PD was defined by a minimum disease duration of five years. The presence of clinical milestones (hallucinations, dementia, recurrent falls, and admission to a nursing home) and mortality was determined based on chart review. Results sNfL was higher in patients with late-stage PD who presented at least one clinical milestone and increased with a higher number of milestones (Spearman’s ρ = 0.66, p

BACKGROUND Phonematic and Semantic Verbal Fluency Tasks (VFT) are widely used to capture cognitive deficits in people with neurodegenerative diseases. Counting the total number of words produced within a given time frame constitutes the most commonly used analysis for VFTs. The analysis of semantic and phonematic word clusters can provide additional information about frontal and temporal cognitive functions. Traditionally, clusters in the semantic VFT are identified by using fixed word lists, which need to be created manually, lack standardization and are language-specific. Furthermore, it is not possible to identify semantic clusters in the phonematic VFT by this technique. OBJECTIVE The objective of this paper was to develop an automated analysis of semantically related word clusters for the semantic and phonematic VFT. Furthermore, we aimed to explore the cognitive domains captured by this analysis for people with Parkinson’s Disease (PwPD). METHODS PwPD performed tablet-based semantic (n=51) and phonematic (n=69) VFT. For both tasks, semantic word clusters were determined using a semantic relatedness model based on a neural network trained on the Wikipedia text corpus. Cluster characteristics were compared to traditional evaluation methods of VFTs and a set of neuropsychological parameters. RESULTS For the semantic VFT, clustering characteristics obtained by automated analyses showed good correlations with the cluster characteristics obtained from the traditional method. Cluster characteristics from automated analyses of phonematic and semantic VFT correlated with the Montreal Cognitive Assessment reporting overall cognitive function, executive functioning reported by Frontal Assessment Battery and Trail Making Test and language function reported by Boston Naming Test. CONCLUSIONS Our study demonstrates the feasibility of standardized automated cluster analyses of VFTs by using semantic relatedness models. These models do not require manually creating and updating categorized word lists and therefore can be easily and objectively implemented in different languages, and potentially allow comparison of results across different languages. Furthermore, this method provides information about semantic clusters in phonematic VFTs that cannot be obtained from traditional methods. Hence, this method could provide easily accessible digital biomarkers for executive and language function in PwPD.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively.ObjectivesTo judge the long-term outcome of patients with STN-DBS.MethodsTo assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001–2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy.ResultsIn the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS.ConclusionsOn average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS.

In Parkinson's disease, postural instability and falls are of particular socioeconomic relevance. Although effective fall prevention and the prophylaxis of fall-related injuries depend on low-threshold symptom monitoring, validated instruments are lacking.ObjectivesTo develop a self-report questionnaire for the assessment of falls, near falls, fear of falling, fall-related injuries, and causes of falls for patients with Parkinson's disease (PwPD).MethodsA pool of potential items was generated from a literature review and by discussion in an expert panel. The first version of the Dresden Fall Questionnaire (DREFAQ) was tested in a group of German-speaking movement disorder specialists as well as PwPD. The resulting 5-item questionnaire was assessed in a validation cohort of 36 PwPD who documented fall events and near-fall events in a calendar for 3 months and completed the DREFAQ at the end of the study. The questionnaire was subsequently used in a separate cohort of 46 PwPD to determine test–retest reliability and confirm the factor structure.ResultsThe DREFAQ showed good internal consistency (Cronbach's α = 0.84) and good test–retest reliability (intraclass correlation coefficient, 0.76; 95% confidence interval, 0.60–0.86). The total DREFAQ score showed good concurrent validity with fall events (Spearman's ρ = 0.82) and near-fall events (Spearman's ρ = 0.78) as determined by fall and near-fall diaries. Factor analysis revealed a 2-factor structure composed of near falls with fear of falling and severe falls with injuries.ConclusionsThe DREFAQ is a reliable and valid 5-item questionnaire for determining the incidence of falls, near falls, fear of falling, fall-related injuries, and causes of falls in PwPD.