Objective: To evaluate whether longitudinal changes in cognitive performance are present in isolated REM sleep behaviour disorder (iRBD) and probable RBD (pRBD, positive single-item RBD questionnaire²), and whether cognitive deficits can be detected remotely across prodromal risk groups.

Background: PREDICT-PD is an online cohort study identifying individuals at risk of Parkinson’s disease (PD). Cognitive deficits are early features of synucleinopathies and occur in iRBD¹. However, cognitive changes in pRBD, especially in relation to olfactory dysfunction and prodromal risk, remain insufficiently characterised. Variability in performance may represent a sensitive marker of early neurodegenerative processes.

Method: This longitudinal study compared cognitive performance in PSG-confirmed iRBD, pRBD with poor smell (hyposmia), pRBD with normal smell, and controls. Cognition was assessed using a web-based Trail Making Test (TMT), measuring processing speed (TMT-A: sequential numbers) and executive function (TMT-B: alternating numbers and letters), developed for remote use in PREDICT-PD and completed at four annual timepoints. Cases were propensity score-matched to controls (1:5) by age and sex. Intra-individual variability was quantified using mean square successive differences (MSSD) and heteroscedastic mixed-effects models assessing whether variability changed across visits.

Results: Participants with PSG-iRBD (n=34) vs controls (n=449) demonstrated greater variability in processing speed and executive function compared to controls (MSSD p=0.015 and 0.020), confirmed by the model (LRT p<0.001). Hyposmic pRBD participants (n=92) vs controls (n=425) showed greater variability in TMT-B reaction time and executive function (MSSD p=0.034 and 0.010), with modelling indicating significant changes in variability across visits (both p<0.001). In normosmic pRBD participants (n=494) vs controls (n=1258) no group differences in TMT variability were observed (all MSSD p≥0.111), although heteroscedastic models indicated that variability in cognitive performance changed across visits (all LRT p<0.001).

Conclusion: Fluctuating cognitive performance is detected in prodromal PD, particularly in PSG-iRBD and hyposmic pRBD. These findings suggest that cognitive instability may precede sustained decline and could provide an early indicator of emerging neurodegeneration.

References: 1 Lyu, Z. et al. Olfactory impairment as an early marker of Parkinson’s disease in REM sleep behaviour disorder: a systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry 92, 271–281 (2021).
2 Postuma RB, Arnulf I, Hogl B, Iranzo A, Miyamoto T, Dauvilliers Y, Oertel W, Ju YE, Puligheddu M, Jennum P, Pelletier A. A single‐question screen for rapid eye movement sleep behavior disorder: a multicenter validation study. Movement Disorders. 2012 Jun;27(7):913-6.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-cognitive-variability-in-isolated-and-probable-rem-sleep-behaviour-disorder-using-the-trail-making-test/