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RESEARCH PAPER ANALYSIS

Depression and cognition mediated rapid eye movement sleep behavior disorder to improve the activities of daily living in Parkinson's disease patients.

Longitudinal analysis of 337 PPMI patients shows that depression and cognitive impairment independently and jointly mediate the effect of REM sleep behavior disorder on activities of daily living in PD, with mediating effects increasing over time.

PMID41938857
JournalFrontiers in psychiatry
Publication Date2026-01-01
Ingested2026-04-28 08:58 PM
EXECUTIVE SUMMARY

What the AI sees

Longitudinal analysis of 337 PPMI patients shows that depression and cognitive impairment independently and jointly mediate the effect of REM sleep behavior disorder on activities of daily living in PD, with mediating effects increasing over time.

WHY IT MATTERS

Research significance

Provides clinically actionable insight that early detection and treatment of depression and cognitive decline (and possibly RBD-targeted care) could preserve function in PD, though it offers limited mechanistic or molecular therapeutic targets for drug discovery.

ABSTRACT

Source abstract

INTRODUCTION: Rapid eye movement sleep behavior disorder (RBD) aggravates cognitive impairment and depression in patients with Parkinson's disease (PD) and significantly compromises their activities of daily living (ADL). This study aimed to explore the potential mediation roles of depression and cognitive impairment between RBD and ADL in PD patients. METHODS: Data from the Parkinson's Progression Markers Initiative (PPMI) database comprised 337 patients. RBD, ADL, depression, and cognitive function were assessed with validated rating scales. Bayesian dynamic mediation analysis was employed to evaluate the separate mediating effects of depression and cognition in mediating RBD and ADL with the time variable (9 times) standardized to the interval [0, 1] via min-max normalization. Multiple time-varying causal mediation analysis was used to assess the role of depression and cognition together in mediating RBD and ADL. RESULTS: At the second follow-up (0.25), the fourth follow-up (0.50), and the sixth follow-up (0.75), the Bayesian dynamic indirect mediating effect of depression between RBD and ADL were 0.058 (95%CI 0.039-0.077), 0.065 (95%CI 0.046-0.084), 0.082 (95%CI 0.061-0.103). The corresponding time-function curve revealed that the mediating effect of depression gradually increased with time. At the 0.25, 0.50, 0.75 standardized time points, the Bayesian dynamic indirect mediating effect of cognition between RBD and ADL were 0.062 (95%CI 0.038-0.086), 0.087 (95%CI 0.044-0.130), 0.136 (95%CI 0.096-0.176), and its time-function curve likewise indicated an increasing trend over time. The joint mediating analysis of the bidirectional decomposition method of the multiple time-varying causal mediation model confirmed that the joint mediating effect of depression and cognition between RBD and ADL was 7.42 (95%CI 4.48-10.36). DISCUSSION: This study demonstrates that depression and cognition can work independently and together, and that reducing depressive symptoms or improving cognition can mediate the reduction of RBD to improve the ADL of PD patients. Notably, this mediating effect gradually intensifies as the duration of the disease progresses. These findings highlight that for PD patients, preventing emotional depression and cognitive decline in the early stage of the disease may reduce the damage caused by RBD.

SUPPORTING PAPER SET

32 more papers to review

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Frontiers in clinical diabetes and healthcare 80.0 7 Neuroprotective effects of GLP-2 and a GLP-2/GIP dual receptor agonist in an MPTP-induced mouse model of Parkinson's disease. Peptides 86.0 8 TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation. Nature communications 91.5 9 Lipid Metabolism and Neurodegeneration: Mechanistic Insights and Therapeutic Targets. Ageing research reviews 82.0 10 Shared functional microbiome signatures in Parkinson's disease and constipation predominate irritable bowel syndrome despite taxonomic divergence. Brain, behavior, & immunity - health 80.0 11 Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases. ChemMedChem 74.0 12 Biomimicking neuromelanin reverses the gait deficits and dopaminergic neuronal loss in the Parkinson's disease. Colloids and surfaces. B, Biointerfaces 86.0 13 Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. Experimental physiology 84.0 14 Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease. Neurotoxicity research 70.0 15 Nanostructured Lipid Carriers Enhance Brain Delivery and Antioxidant Efficacy of a Small-Molecule MAO B Inhibitor for Neurodegenerative Disease Therapy. Molecular pharmaceutics 78.0 16 Pathophysiological Role of the Gut Brain Axis in Parkinson's Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation. Current neurovascular research 86.0 17 Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review. Current issues in molecular biology 86.0 18 Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders. Neuroprotection (Chichester, England) 76.0 19 Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Computers in biology and medicine 65.0 20 Models of neuroprotection in Parkinson's disease: Exploring cellular, molecular, and microenvironmental targets. Experimental neurology 78.0 21 Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy. Frontiers in pharmacology 75.2 22 Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy. Frontiers in pharmacology 75.0 23 Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities. Cell death discovery 82.0 24 Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions. Frontiers in microbiology 74.0 25 Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review. Biomolecules & biomedicine 84.0 26 Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights. Current neurovascular research 76.0 27 Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses. The Journal of steroid biochemistry and molecular biology 82.0 28 Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential. Cell stress 83.3 29 Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease. Central nervous system agents in medicinal chemistry 64.0 30 Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder. Signal transduction and targeted therapy 84.0 31 HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches. Inflammopharmacology 78.0 32 Beyond acid-base dyshomeostasis: Dynamic instability of neuronal lysosomal pH as a pathogenic mechanism and therapeutic target in neurological diseases. Biochemical pharmacology 88.0
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