Abstract Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia. Mounting evidence positions RBD as a critical prodromal indicator of synucleinopathies—particularly Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA)—with a significant link to progressive cognitive decline. To explore the underlying pathophysiological mechanisms connecting RBD with cognitive impairment, to delineate the neuropsychological profile of the affected individuals, and to critically evaluate the current diagnostic tools and therapeutic challenges. We synthesized data from clinical cohort studies, structural and functional neuroimaging modalities (magnetic resonance imaging MRI, fluorodeoxyglucose positron-emission tomography FDG-PET, and single-photon emission computed tomography SPECT), molecular biomarkers—including alpha-synuclein seeding assays—and genetic studies focusing on mutations such as glucocerebrosidase, β, acid (GBA) and synuclein alpha (SNCA). Individuals with idiopathic RBD (iRBD) frequently exhibit early deficits in executive function, attention, visuospatial abilities, and episodic memory—often years before motor symptoms manifest. Pathologically, the spread of alpha-synuclein aggregates from REM sleep-regulating nuclei in the brainstem to limbic and neocortical areas mirrors the trajectory of cognitive decline. Cholinergic-system degeneration, particularly in the pedunculopontine nucleus and basal forebrain, further contributes to the neurocognitive symptoms. Neuroimaging consistently reveals frontal and temporal cortical thinning, along with posterior hypometabolism characteristic of synucleinopathies. Biomarker analysis shows altered cerebrospinal fluid (CSF) amyloid-beta and -tau levels, as well as positive alpha-synuclein real-time quaking-induced conversion (RT-QuIC) assay results. Genetic predispositions strongly influence the risk and rate of progression. A powerful early biomarker for cognitive decline associated with synucleinopathies, the early identification of RDB through comprehensive neuropsychological profiling, advanced imaging techniques, and molecular diagnostic methods is essential for risk stratification and monitoring. Although disease-modifying therapies remain elusive, a deeper understanding of shared pathogenic pathways offers promising avenues for targeted neuroprotective strategies.
Faezeh Khorshidian (Sun,) studied this question.