Objective Given the clinical heterogeneity of Parkinson's disease (PD), identification of early -stage subgroups with shared non-motor symptom (NMS) profiles may clarify its pathophysiology. This study used latent-profile analyses (LPA) to define subgroups based on sleep disturbances, cognitive performance and neuropsychiatric symptoms, and examined dopaminergic function and brain volume differences between them.<br /> Methods We analyzed data from 51 cognitively normal non-PD older adults and 105 early-stage PD participants from the iPARK trial, including 19 who underwent [11C]-raclopride PET/MR. Participants completed the Hospital Anxiety and Depression Scale, the short version of the Karolinska Sleep Questionnaire and a battery of neuropsychological tests. LPA were used in PD to identify subgroups based on NMS profiles, which were then characterized and examined in relation to dopaminergic integrity and brain morphology.<br /> Results LPA identified a two-cluster solution as the best fit. Group 1 (N = 49) showed poorer working memory, executive function and processing speed along with greater daytime sleepiness, depression and anxiety. Group 2 (N = 56) exhibited less affected cognitive function and minimal NMS. Groups were similar in demographics, disease duration, motor symptom severity and medication, but differed on UPDRS-1 NMS. Group 1 demonstrated significantly reduced [11C]-raclopride binding potential compared to Group 2 in the left putamen at both ROI- and voxel-wise analysis.<br /> Conclusion These findings indicate clinically distinct subgroups in early-stage PD. Greater NMS burden is linked to impaired dopaminergic integrity, suggesting a potential neurobiological signature. Early identification of such subgroups may improve understanding of disease heterogeneity and support personalized management and interventions.

Clinical trial registration https://clinicaltrials.gov/study/NCT03680170?id=NCT03680170&rank=1, identifier (NCT03680170).

Cognitive deficits are common in Parkinson’s disease (PD) and reduce quality of life, yet they are often overlooked in clinical practice and respond poorly to standard medication. Working memory updating (WMU) training has shown to improve WMU performance and dopaminergic availability in healthy populations. As PD is characterized by dopaminergic depletion, WMU training may represent a promising intervention. This thesis investigated the feasibility, effects, and experience of WMU training in people with PD.

A feasibility study and single-subject study (Study I) indicated that WMU training is feasible, and improvements were observed in cognition, motor function, and functional brain response.

In Study II, 86 people with PD were randomized to 30 sessions of WMU training or active control. Findings demonstrated improvements immediately after training for the WMU group on cognitive tests that share cognitive processes with the training tasks, and these gains were maintained four months after training. Broader cognitive improvements were observed at follow-up, suggesting delayed transfer effects to untrained domains. Self-reported psychological health remained stable.

Study III focused on the experience of cognitive training via semi-structured interviews with 18 people with PD. Three themes were identified: commitment to the training, receiving feedback during training, and inspiration to apply strategies from training to everyday life.

In sum, this thesis provides evidence that WMU training in people with PD is feasible and leads to measurable cognitive benefits. Improvements were observed on tasks that share cognitive processes with the training, and after four months in broader cognitive domains. The findings further indicate that emotional, motivational, and metacognitive processes develop during training and transfer to everyday life. Together, these results suggest that WMU training can enhance aspects of cognitive ability and cognitive efficiency in people with PD.

Cognitive deficits are common in people with Parkinson’s disease (PD), reduce quality of life, and are poorly addressed by medication. This thesis investigated whether working memory updating (WMU) training can represent a promising cognitive intervention for people with PD. Across three studies, including a feasibility study, a randomized controlled trial, and a qualitative study, the thesis examined the feasibility, effects, and experience of WMU training. The results showed that WMU training is feasible and leads to measurable cognitive improvements. Immediate gains were observed on tasks that share cognitive processes with the training, and delayed improvements in broader cognitive domains. Participants also described emotional, motivational, and metacognitive changes during training that supported transfer to everyday life. Together, these findings may suggest that WMU training enhances both cognitive ability and cognitive efficiency in people with PD.

Meta-analyses on cognitive training (CT) for people with Parkinson's Disease (PD) report improvements in global cognition and it is recommended as a treatment for people with PD with mild cognitive impairment. However, few studies have assessed the experience of CT. Therefore, this study explored the experience of process-based CT in people with PD and focused on how participants engaged with and made use of the training in their everyday life. In this study, semi-structured, individual interviews were conducted with 18 people with PD who had completed 6-8 weeks of process-based CT. Reflexive thematic analysis was used to analyse the data. Three overarching themes were developed that reported on the participants' (1) dedication towards CT; (2) meaning of seeing change in cognitive performance during CT; and (3) inspiration to transfer the knowledge, strategies and mindset from training into everyday life. Furthermore, a route to transfer was described including emotional and motivational experiences. In conclusion, CT was experienced in an active, reflective manner whereby emotional and cognitive challenges during training are dealt with and are seen as important ingredients to attain transfer to everyday life. Future studies are encouraged to examine the link between such qualitative findings and quantitatively measured outcomes.Trial registration: ClinicalTrials.gov identifier: NCT03680170..

Background:& nbsp;Dance as a treatment to support physical, cognitive and emotional functioning, has gained increased acceptance as a healthcare intervention for people with Parkinson's Disease (PD). The impact of the COVID-19 pandemic has been far reaching with devastating effects for at-risk populations. To find alternative and safe treatment delivery options during the pandemic has been of utmost importance. The purpose of this mixed-methods study was to evaluate the feasibility and the experience of digital dance for people with PD (Dance for PD (c)) and to examine change in self-reported quality of life, psychological health, subjective cognitive complaints and mental fatigue.Methods:& nbsp;23 participants with PD (mean age 70) partook in 10-h weekly digital Dance for PD sessions. Feasibility outcome measures were assessed at post-test. Web-based questionnaires examining quality of life, subjective memory complaints, depression, anxiety and mental fatigue were administered at pre- and post-test. Moreover, nine participants partook in focus group discussions at post-test.Results:& nbsp;The results showed an acceptable feasibility to home-based digital Dance for PD, where 86% of the dance classes were completed, only minor negative side effects were reported (i.e., sore joints), and all experienced the dance classes as motivating and safe to do at home. The majority also reported positive effects on mood and physical functioning. The results from the questionnaires showed significant improvements in depressive symptoms (p = 0.006) and quality of life (p < 0.001) at post-test. In the focus groups, participants indicated that digital dance was a beneficial and enjoyable activity with a strong added value during the COVID-19 pandemic. Nevertheless, they experienced that digital dance missed some important elements of live dance.Conclusions:& nbsp;This study showed that digital Dance for PD is feasible and holds promise as a viable and safe method to keep people with PD dancing even when physical meetings are not possible. Beyond the pandemic, digital dance could be applied to a wide variety of patient groups including rural populations and patients for whom transportation may not be feasible for practical or financial reasons.

In Parkinson’s disease (PD), the fronto-striatal network is involved in motor and cognitive symptoms. Working memory (WM) updating training engages this network in healthy populations, as observed by improved cognitive performance and increased striatal BOLD signal. This two-part study aimed to assess the feasibility of WM updating training in PD and measure change in cognition, movement and functional brain response in one individual with PD after WM updating training. A feasibility and single-subject (FL) study were performed in which patients with PD completed computerized WM updating training. The outcome measures were the pre-post changes in criterion and transfer cognitive tests; cognitive complaints; psychological health; movement kinematics; and task-related BOLD signal. Participants in the feasibility study showed improvements on the criterion tests at post-test. FL displayed the largest improvements on the criterion tests and smaller improvements on transfer tests. Furthermore, FL reported improved cognitive performance in everyday life. A shorter onset latency and smoother upper-limb goal-directed movements were measured at post-test, as well as increased activation within the striatum and decreased activation throughout the fronto-parietal WM network. This two-part study demonstrated that WM updating training is feasible to complete for PD patients and that change occurred in FL at post-test in the domains of cognition, movement and functional brain response.

Background: Cognitive decline and dementia are common in Parkinson's disease (PD). Cognitive deficits have been linked to the depletion of dopamine in the nigrostriatal pathway, but pharmacological treatments for PD have little evidence of improving or delaying cognitive decline. Therefore, exploring non-pharmacological treatment options is important. There have been some promising results of cognitive training interventions in PD, especially for improvements in working memory and executive functions. Yet, existing studies are often underpowered, lacking appropriate control condition, long term follow-up, a thorough description of the intervention and characteristics of the participants. Working memory updating training has previously shown to increase striatal activation in healthy young and old participants as well as dopaminergic neurotransmission in healthy young participants. In the light of dopamine dysfunction in PD, with negative effects on both motor and cognitive functions it is of interest to study if an impaired striatal system can be responsive to a non-invasive, non-pharmacological intervention. Methods and design: The iPARK trial is a double-blinded, randomized controlled trial with a parallel-group design that aims to recruit 80 patients with PD (during the period 02/2017-02/2023). Included patients need to have PD, Hoehn and Yahr staging I-III, be between 45 to 75 years of age and not have a diagnosis of dementia. All patients will undergo 30 sessions (6-8 weeks) of web-based cognitive training performed from home. The target intervention is a process-based training program targeting working memory updating. The placebo program is a low dose short-term memory program. A battery of neuropsychological tests and questionnaires will be performed before training, directly after training, and 16 weeks after training. Discussion: We expect that the iPARK trial will provide novel and clinically useful information on whether updating training is an effective cognitive training paradigm in PD. Further, it will hopefully contribute to a better understanding of cognitive function in PD and provide answers regarding cognitive plasticity as well as determining critical factors for a responsive striatal system.