Long-term effects of cognitive training in Parkinson's disease: A randomized, controlled trial.

Background: Computerized cognitive training may be promising to improve cognitive impairment in Parkinson's disease and has even been suggested to delay cognitive decline. However, evidence to date is limited. The aim of this study was to assess the durability of eight-week cognitive training effects at up to two years follow-up. Methods: One hundred and thirty-six (1 3 6) individuals with Parkinson's disease, subjective cognitive complaints but without severe cognitive impairment (Montreal Cognitive Assessment ≥ 22) participated in this double-blind RCT. Participants underwent an eight-week home-based intervention of either adaptive, computerized cognitive training with BrainGymmer (n = 68) or an active control (n = 68). They underwent extensive neuropsychological assessment, psychiatric questionnaires and motor symptom assessment at baseline and one and two years after the intervention. We used mixed-model analyses to assess changes in cognitive function at follow-up and performed Fisher's exact tests to assess conversion of cognitive status. Results: There were no group differences on any neuropsychological assessment outcome at one- and two-year follow-up. Groups were equally likely to show conversion of cognitive status at follow-up. A considerable amount of assessments was missed (1y: n = 27; 2y: n = 33), most notably due to COVID-19 regulations. Conclusions: Eight-week cognitive training did not affect long-term cognitive function in Parkinson's disease. Future studies may focus on one cognitive subgroup to enhance reliability of study results. Intervention improvements are needed to work towards effective, lasting treatment options.

Effect of eight-week online cognitive training in Parkinson's disease: A double-blind, randomized, controlled trial.

INTRODUCTION: Cognitive training (CT) has been proposed as a treatment option for cognitive impairment in Parkinson's disease (PD). We aimed to assess the efficacy of adaptive, computerized CT on cognitive function in PD. METHODS: In this double-blind, randomized controlled trial we enrolled PD patients that experienced substantial subjective cognitive complaints. Over a period of eight weeks, participants underwent 24 sessions of computerized multi-domain CT or an active control intervention for 45 min each (randomized 1:1). The primary outcome was the accuracy on the Tower of London task; secondary outcomes included effects on other neuropsychological outcomes and subjective cognitive complaints. Outcomes were assessed before and after training and at six-months follow-up, and analyzed with multivariate mixed-model analyses. RESULTS: The intention-to-treat population consisted of 136 participants (n = 68 vs. n = 68, age M: 62.9y, female: 39.7%). Multivariate mixed-model analyses showed no group difference on the Tower of London accuracy corrected for baseline performance (n = 130): B: -0.06, 95% CI: -0.27 to 0.15, p = 0.562. Participants in the CT group were on average 0.30 SD (i.e., 1.5 s) faster on difficulty load 4 of this task (secondary outcome): 95% CI: -0.55 to -0.06, p = 0.015. CT did not reduce subjective cognitive complaints. At follow-up, no group differences were found. CONCLUSIONS: This study shows no beneficial effect of eight-week computerized CT on the primary outcome (i.e., planning accuracy) and only minor improvements on secondary outcomes (i.e., processing speed) with limited clinical impact. Personalized or ecologically valid multi-modal intervention methods could be considered to achieve clinically meaningful and lasting effects.

The cost-effectiveness of specialized nursing interventions for people with Parkinson's disease: the NICE-PD study protocol for a randomized controlled clinical trial.

BACKGROUND: Current guidelines recommend that every person with Parkinson's disease (PD) should have access to Parkinson's disease nurse specialist (PDNS) care. However, there is little scientific evidence of the cost-effectiveness of PDNS care. This hampers wider implementation, creates unequal access to care, and possibly leads to avoidable disability and costs. Therefore, we aim to study the (cost-)effectiveness of specialized nursing care provided by a PDNS compared with usual care (without PDNS) for people with PD in all disease stages. To gain more insight into the deployed interventions and their effects, a preplanned subgroup analysis will be performed on the basis of disease duration (diagnosis < 5, 5-10, or > 10 years ago). METHODS: We will perform an 18-month, single-blind, randomized controlled clinical trial in eight community hospitals in the Netherlands. A total of 240 people with PD who have not been treated by a PDNS over the past 2 years will be included, independent of disease severity or duration. In each hospital, 30 patients will randomly be allocated in a 1:1 ratio to receive either care by a PDNS (who works according to a recent guideline on PDNS care) or usual care. We will use two co-primary outcomes: quality of life (measured with the Parkinson's Disease Questionnaire-39) and motor symptoms (measured with the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III). Secondary outcomes include nonmotor symptoms, health-related quality of life, experienced quality of care, self-management, medication adherence, caregiver burden, and coping skills. Data will be collected after 12 months and 18 months by a blinded researcher. A healthcare utilization and productivity loss questionnaire will be completed every 3 months. DISCUSSION: The results of this trial will have an immediate impact on the current care of people with PD. We hypothesize that by offering more patients access to PDNS care, quality of life will increase. We also expect healthcare costs to remain equal because increases in direct medical costs (funding additional nurses) will be offset by a reduced number of consultations with the general practitioner and neurologist. If these outcomes are reached, wide implementation of PDNS care will be warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03830190. Registered February 5, 2019 (retrospectively registered).

COGTIPS: a double-blind randomized active controlled trial protocol to study the effect of home-based, online cognitive training on cognition and brain networks in Parkinson's disease.

BACKGROUND: Cognitive dysfunction is highly prevalent in Parkinson's disease (PD) and a large proportion of patients eventually develops PD-related dementia. Currently, no effective treatment is available. Cognitive training is effective in relieving cognitive dysfunctions in several -neurodegenerative- diseases, and earlier small-scale trials have shown positive results for PD. In this randomized controlled trial, we assess the efficacy of online home-based cognitive training, its long-term effects, as well as the underlying neural correlates in a large group of PD patients. METHODS: In this double-blind randomized controlled trial we will include 140 non-demented patients with idiopathic PD that experience significant subjective cognitive complaints. Participants will be randomized into a cognitive training group and an active control group. In both groups, participants will individually perform an online home-based intervention for eight weeks, three times a week during 45 min. The cognitive training consists of thirteen games that focus on executive functions, attention and processing speed with an adaptive difficulty. The active control comprises three games that keep participants cognitively engaged without a training component. Participants will be subjected to extensive neuropsychological assessments at baseline and after the intervention, and at six months, one year and two years of follow-up. A subset of participants (40 in each treatment condition) will undergo structural and functional magnetic resonance imaging. The primary outcome of this study is the performance on the Tower of London task. Secondary outcomes are objective and subjective cognitive functioning, conversion to PD-related mild cognitive impairment or dementia, functional and structural connectivity and network topological indices measured with magnetic resonance imaging. None of the outcome measures are part of the cognitive training program. Data will be analyzed using multivariate mixed-model analyses and odds ratios. DISCUSSION: This study is a large-scale cognitive training study in PD patients that evaluates the efficacy in relieving cognitive dysfunction, and the underlying mechanisms. The strengths of this study are the large sample size, the long follow-up period and the use of neuroimaging in a large subsample. The study is expected to have a low attrition and a high compliance rate given the home-based and easily-accessible intervention in both conditions. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02920632 . Registered September 30, 2016.