Objective: We aimed to derive a DLB-related structural MRI pattern based on cortical and subcortical morphometry and investigate whether this pattern predicts phenoconversion and clinical progression in individuals with iRBD.

Background: Idiopathic REM sleep behavior disorder (iRBD) is one of the strongest prodromal conditions of Lewy body diseases, including dementia with Lewy bodies (DLB) and Parkinson’s disease. However, biomarkers capable of predicting the clinical trajectory of phenoconversion, particularly dementia-first progression, remain limited.

Method: A total of 186 participants were included: 45 healthy controls (HC), 99 patients with iRBD, and 42 patients with clinically diagnosed DLB. Structural MRI features derived from cortical thickness and subcortical volumetry were used to generate a DLB-related structural pattern discriminating DLB from HC. The derived pattern score was subsequently applied to the iRBD cohort.  Longitudinal trajectories of the structural pattern score were examined according to phenoconversion subtype, and correlations between the structural pattern and neuropsychological measures were analyzed.

Results: The MRI-derived cortical–subcortical structural pattern distinguished DLB from HC with high accuracy (AUC = 0.9437). In the iRBD cohort, a higher DLB pattern score significantly predicted future conversion to dementia (hazard ratio 7.52, p = 0.000188). Temporal trajectory analysis demonstrated that motor-first converters crossed the structural pattern cutoff (score 1.2) approximately 1.6 years before clinical conversion, whereas dementia-first converters crossed this threshold markedly earlier, at approximately 5.4 years prior to conversion. Longitudinal analysis showed a graded progression of DLB pattern scores, with the highest levels observed in dementia converters, followed by motor-first converters and non-converters. Higher structural pattern scores were associated with worse cognitive performance, demonstrating negative correlations with Digit Span (p = 0.048), SVLT immediate recall (p = 0.0059), and COWAT (p = 0.0001).

Conclusion: The DLB-related structural pattern may provide a practical and accessible biomarker for identifying iRBD patients at high risk of dementia-dominant progression and may facilitate early stratification for future disease-modifying trials in prodromal Lewy body disorders.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cortical-subcortical-structural-signature-of-dementia-with-lewy-bodies-reveals-cognitive-trajectories-of-lewy-body-disease-in-rem-sleep-behavior-disorder/