CogTrAiL-RBD
Cognitive training and promoting a healthy lifestyle in isolated REM sleep behavior disorder: The randomized controlled trial CogTrAiL-RBD
Clinical Question
Does a 5-week digital, adaptive, multidomain cognitive training combined with a healthy lifestyle module improve executive function in individuals with isolated REM sleep behavior disorder?
Bottom Line
In individuals with polysomnography-confirmed iRBD, a 5-week digital multidomain cognitive training within a lifestyle-guidance framework was feasible and produced a medium positive effect on executive functions at 6 weeks (d=0.500) that was sustained as a small effect at 6-month follow-up (d=0.397) versus waiting-list control, providing initial evidence of potential cognitive benefits; suitability for secondary dementia prevention in this prodromal Lewy body disease population warrants further investigation.
Major Points
- First RCT of a digital multidomain cognitive training + lifestyle module in polysomnography-confirmed iRBD (n=82).
- Medium positive intervention effect on executive functions at 6 weeks post-allocation (d=0.500, 95% CI 0.221-0.779).
- Effect sustained at 6-month follow-up with a small effect size (d=0.397, 95% CI 0.115-0.679).
- Demonstrates feasibility of a scalable, non-pharmacological, remotely delivered intervention in a prodromal Lewy body disease population.
- Supports iRBD as a well-defined at-risk window analogous to Alzheimer's prevention cohorts for secondary dementia prevention research.
Design
Study Type: Monocentric, single-blind, randomized controlled trial with two parallel arms (superiority design) and an exploratory delayed-start open-label extension
Randomization: 1
Blinding: Single-blind (experimenter-blinded outcome assessment)
Allocation: 1:1 randomization using computerized minimization (R package Minirand) balancing age, sex, and premorbid IQ; central allocation concealment
Enrollment Period: June 14, 2022 to December 13, 2024 (parallel-group phase completed September 5, 2025; open-label phase LPLV April 24, 2026)
Follow-up Duration: 6 months (assessments at baseline t0, 6-week post-allocation t1, and 6-month follow-up t2)
Centers: 1
Countries: Germany
Sample Size: 82
Analysis: Comparison of change from t0 to t1 (short-term) and t0 to t2 (long-term) between intervention and control groups; effect sizes reported as Cohen's d with 95% CIs; robust clinically meaningful improvement (rCMI) also reported
Power Calculation: A priori power analysis with G*Power to detect medium effect (Cohen's d = 0.5) with alpha=0.05, 80% power, accounting for anticipated high baseline-retest correlations in the executive function composite (specific target N truncated in source)
Registration: German Clinical Trials Register DRKS00024898 (registered 2022-03-11); ethics approval University of Cologne 21-1291
Inclusion Criteria
- Polysomnography-proven diagnosis of isolated REM sleep behavior disorder (iRBD)
- Age 40-80 years
- Normal or corrected-to-normal vision and hearing
- Sufficient proficiency in German
- Access to a local computer with internet access
Exclusion Criteria
- Severe cognitive dysfunction (Montreal Cognitive Assessment [MoCA] score <= 22)
- Significant neurological and psychiatric concomitant diseases
- Contraindications for MRI (only for those willing to participate in the optional MRI module)
Arms
| Field | Intervention (INT) | Control |
|---|---|---|
| N | ||
| Intervention | 5-week digital, adaptive, multidomain cognitive training (HeadApp/NEUROvitalis Digital; 15 sessions over 5 weeks, 3 sessions/week, four 10-min tasks per session covering executive functions, working memory, episodic memory, attention, visuo-cognition, language; max total 600 minutes) plus a module promoting a healthy, active lifestyle (psychoeducational booklet adapted from NEUROvitalis + digital activity diaries capturing IPAQ, Lifestyle Activities Questionnaire, MEDAS) | Passive waiting-list control group |
| Duration | 5 weeks of training; follow-up to 6 months | 6 months |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Change in an equally weighted executive function composite score comprising logical reasoning, set-shifting, semantic and phonemic verbal fluency, and interference control (from t0 baseline to post-allocation timepoints) | Primary | t1: Cohen's d = 0.500 (medium); t2: Cohen's d = 0.397 (small) | |||
| Composite z-scores for other cognitive domains (attention & working memory, memory, visuo-cognition, language) and a global cognition composite score derived from these domain scores | Secondary | Not reported in available source text | |||
| Single cognitive test scores and MCI status (exploratory cognitive outcomes) | Secondary | Not reported in available source text | |||
| Subjective cognitive decline (Multi-SubCoDE SCD-Severity) | Secondary | Not reported in available source text | |||
| Depressive symptoms (Beck Depression Inventory, BDI-II total score) | Secondary | Not reported in available source text | |||
| Fatigue (Fatigue Scale for Motor and Cognitive Functions, FSMCF total score) | Secondary | Not reported in available source text | |||
| Health-related quality of life (SF-36 total score) | Secondary | Not reported in available source text | |||
| PD-related motor symptoms (MDS-UPDRS-III total score) | Secondary | Not reported in available source text | |||
| Fine motor dexterity (Purdue Pegboard both-hands and assembly) | Secondary | Not reported in available source text | |||
| Feasibility outcomes: participation rate, compliance (>=80% cognitive training sessions [>=12/15]; consistent activity-diary use [>=3/5 weekly, >=4/6 monthly]), overall dropout rate | Secondary | Not reported in available source text | |||
Criticisms
- Monocentric single-center design limits generalizability
- Small sample size (n=82) for a prevention trial
- Short 5-week intervention compared to long-term multidomain prevention frameworks like FINGER
- Passive waiting-list control does not control for attention/expectancy effects
- Lifestyle module was psychoeducational + self-monitoring only, without personalized counseling, supervised physical activity, or nutritional counseling as in large-scale multidomain trials
- German-speaking, digitally-enabled population may limit external validity
- Follow-up limited to 6 months; effects on phenoconversion to PD/DLB not assessed
Based on: CogTrAiL-RBD (Alzheimer's & Dementia, 2026)
Authors: Ophey A, Röttgen S, Kufer K, ..., Kalbe E
Citation: Alzheimers Dement. 2026 Aug 5;22(8):e71707. doi: 10.1002/alz.71707
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