Cognitive Impairment in isolated REM Sleep Behavior Disorder: a data-driven approach to understanding the heterogeneity of different phenotypes. A pilot study

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STUDY OBJECTIVES: Isolated REM Sleep Behavior Disorder (iRBD) frequently presents with cognitive impairment and may precede overt α-synucleinopathies by decades. Cognitive impairment is present early in the disease course, and patients exhibit a specific pattern of cognitive involvement. This work aims to compare Mild Cognitive Impairment (MCI) in iRBD across diagnostic criteria and identify data-driven cognitive phenotypes. METHODS: We conducted a cross-sectional study including 55 consecutively enrolled vPSG-confirmed iRBD. All subjects underwent a neuropsychological evaluation, and MCI status was derived from the current classification. Data-driven clustering and PCA were performed. Candidate neuropsychological markers of MCI were evaluated using ROC analysis and logistic regression. RESULTS: MCI was found in 60% of the sample. Pathological performance was most frequently observed on executive, attentional, and visuo-spatial measures. Data-driven analysis identified three distinct cognitive profiles within MCI-RBD: (a) a memory-executive subgroup, (b) a globally impaired subgroup, and (c) a mild-preserved subgroup with performance near normality. PCA identified a prominent global cognitive efficiency factor and a secondary component that differentiated "dysexecutive" from other profiles. The best discriminative measures for MCI status were TMT-B (AUC = .85), TMT B-A (AUC = .84), and MWCST perseverative errors (AUC = .83). CONCLUSIONS: Cognitive impairment in iRBD is common and heterogeneous. Data-driven analyses suggest three distinct cognitive profiles within MCI-RBD, with executive-attentional dysfunction emerging as a prominent feature and potentially representing a key target for cognitive evaluation and risk stratification. These findings support an executive-focused conceptualization of MCI-RBD and highlight the need for in-depth cognitive investigation and the harmonization of neuropsychological measures to facilitate comparability.

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