CogTrAiL-RBD (Germany)

Cognitive Training & a Healthy, Active Lifestyle Program for People with Isolated REM Sleep Behaviour Disorder: CogTrAiL-RBD

Isolated REM sleep behavior disorder (iRBD) is a prodromal phase of Lewy body diseases and associated with a high risk for cognitive decline. Therefore, iRBD provides a suitable window for early intervention. The CogTrAiL-RBD trial investigates the feasibility and effectiveness of digital, adaptive, multidomain cognitive training alongside a healthy lifestyle module for individuals with iRBD. The findings demonstrate that the combined intervention is feasible and can produce clinically meaningful improvements in executive function in this target group.

Latest page update: 15 July, 2026

Aims of the project

To assess feasibility and the potential to induce cognitive plasticity via cognitive training alongside a module promoting a healthy active lifestyle in individuals with isolated REM sleep behavior disorder (iRBD), which is considered a prodromal phase of Parkinson’s disease and dementia with Lewy bodies.

Location

Germany

Local setting

Participants were consecutively recruited from continuously expanding local iRBD cohorts in the Rhineland (Cologne, Bonn, Aachen; Germany).

During active recruitment for the local iRBD cohorts, we ensured informed decision-making and autonomy in the risk disclosure process from the outset. Within the local iRBD cohort settings, individuals with iRBD are comprehensively characterized through clinical and biological assessments and are invited to participate in annual clinical follow-up visits.

Organizations involved

University Hospital Cologne
Research Center Juelich
University Hospital Bonn

Principal Investigator (PI)

Dr. Anja Ophey
Department of Medical Psychology | Neuropsychology and Gender Studies, Center for Neuropsychological Diagnostics and Intervention (CeNDI), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

Research team

Prof. Dr. Michael Sommerauer
Department of Parkinson, Sleep and Movement Disorders, Center for Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany

Prof. Dr. Elke Kalbe
Department of Medical Psychology | Neuropsychology and Gender Studies, Center for Neuropsychological Diagnostics and Intervention (CeNDI), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

Duration of the intervention

Project start date

Project end date

Current stage of the project

Completed

Number of study participants

Target population

Individuals with a polysomnography-proven diagnosis of iRBD

RBD is a parasomnia characterized by loss of muscle atonia and dream enactment during REM sleep. Approximately, 80-90% of individuals with isolated or idiopathic RBD (iRBD) show seeding competent α-synuclein species in skin or cerebrospinal fluid, illustrating iRBD biologically as an early α-synucleinopathy. Accordingly, up to 90% of individuals with iRBD will eventually phenoconvert to clinical manifest Parkinson’s disease or dementia with Lewy bodies within 15 years after diagnosis. Approximately 25-30% of people with iRBD already meet criteria for mild cognitive impairment (MCI), with its presence tripling the risk of subsequent phenoconversion. IRBD thus represents a predictable pre-diagnostic phase, analogous to the “at-risk” cohorts targeted in Alzheimer’s prevention research, and provides a well-defined window for implementing neuroprotective and cognition-preserving interventions.

Outcomes

Primary outcomes

Equally weighted composite score of executive functions comprising subscores of logical reasoning, set-shifting, semantic and phonemic verbal fluency, and interference control

Secondary outcomes

• Equally weighted composite scores for other cognitive domains (attention & working memory, memory, visuo-cognition, and language) and global cognition
• participant-reported outcome measures (PROMs): subjective cognitive decline (Multi-SubCoDE SCD-Severity), depressive symptoms (BDI-II total score), fatigue (FSMCF total score), and health-related quality of life (SF-36 total score)
• motor outcomes: PD-related motor symptoms (MDS-UPDRS-III total score) and fine motor dexterity (Purdue Pegboard both-hands and assembly)

Exploratory outcomes

• Single cognitive test scores
• MCI status
• Accelerometry
• Structural and functional MRI

Intervention

The study has 2 study arms:

• Intervention group (INT): 2 x 5-week digital cognitive training alongside a module promoting a healthy, active lifestyle
• Delayed-start control group (CON): passive control group in the parallel-group phase, 5-week digital cognitive training alongside a module promoting a healthy, active lifestyle in the open-label phase.

Domains

• Digital, adaptive, multidomain cognitive training
• Psychoeducational content (e.g., risk and protective factors for healthy aging, the concepts of cognitive and motor reserve, strategies for incorporating cognitive, social, and physical activities into daily routines, and the role of the Mediterranean diet for cognitive health)
• Activity self-monitoring (physical activity, cognitive and social lifestyle activities, and Mediterranean diet adherence)

Results

Primary outcomes

For the executive functions composite score we found a significant time*group interaction with a medium effect size at post-test (Cohen’s d = 0.500, 95%CI [0.221,0.779]) and a small effect size at 6-month follow-up (Cohen’s d = 0.397, 95%CI [0.115,0.679]). Results of the open-label phase are still pending.

Secondary outcomes

No significant time*group interactions were observed for other domain-wise secondary cognitive outcomes, secondary motor outcomes (MDS-UPDRS-III, Purdue Pegboard both-hands, Purdue Pegboard assembly), and secondary PROMs (Multi-SubCoDE SCD-Severity, BDI-II, FSMCF, SF-36). Results of the open-label phase are still pending.

Others

For PROMs, including subjective cognitive decline, depressive symptoms, and fatigue, main effects of timepoint were found, indicating reduced symptom severity over time independent of group assignment. Results of exploratory outcomes and the open-label phase are still pending.

Acknowledgements

The setup and start of the CogTrAiL-RBD study were supported by the Koeln Fortune Program / Faculty of Medicine, University of Cologne (grant no. 329/2021, Dr. Anja Ophey) and the “Novartis-Stiftung für therapeutische Forschung” (Dr. Anja Ophey).