[Neurodegenerative Diseases and Isolated REM Sleep Behavior Disorder]

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a parasomnia characterized by dream-enacting behaviors caused by the loss of muscle atonia during REM sleep. It is widely recognized as a prodromal phase of α-synucleinopathies such as Parkinson's disease and dementia with Lewy bodies. Longitudinal cohort and pathological studies have demonstrated that approximately 70% of patients with iRBD develop defined neurodegenerative disorders within 10 years. Recent advances have identified several promising biomarkers to predict phenoconversion, including dopamine transporter imaging (DaT SPECT), cerebrospinal fluid α-synuclein detected via RT-QuIC, decreased CSF Aβ42, and elevated CSF/serum albumin ratio indicating blood-brain barrier dysfunction. Moreover, functional magnetic resonance imaging studies have revealed altered connectivity in the frontostriatal and posterior cortical networks in patients with iRBD, which correlates with cognitive and motor symptoms. These multimodal markers have significant potential for stratifying phenoconversion risks and guiding early therapeutic interventions. Future efforts should focus on standardizing biomarker assays and validating them through multicenter longitudinal studies to enhance diagnostic precision and support disease-modifying clinical trials in the prodromal phase of Lewy body diseases.