The Role of the Choroid Plexus in Cognitive Impairment Across Neurological Disorders: A Systematic Review

Introduction: Choroid plexus volume (CPV), a structural marker linked to CSF regulation and neuroimmune activity, has emerged as a potential indicator of cognitive vulnerability across neurological disorders. This systematic review synthesizes evidence on CPV–cognition relationships in Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, multiple sclerosis, and related conditions. Methods Following PRISMA guidelines and a PROSPERO-registered protocol, five databases (PubMed, Scopus, Web of Science, Embase, PsycINFO) were searched through October 2025. Eligible human studies used structural MRI to quantify CPV and reported cognitive outcomes. Two independent reviewers conducted screening, data extraction, and quality assessment using the Newcastle–Ottawa Scale. Results 15 studies met inclusion criteria. Across the Alzheimer continuum CP enlargement consistently correlated with poorer global cognition, executive dysfunction, and episodic memory impairment. Longitudinal studies showed that greater CPV predicted faster cognitive decline and stronger amyloid-related pathology. In Parkinson disease, reduced CPV in de novo patients and CP enlargement in later stages were both associated with worse cognition and increased risk of dementia. In multiple sclerosis and white matter hyperintensities -related vascular aging, larger CPV was linked to deficits in processing speed, executive functioning, global cognition, and fatigue. Mechanistic evidence highlighted impaired CSF and glymphatic clearance, amyloid and α-synuclein accumulation, neuroinflammation, and microstructural CP changes as mediators of CPV-related cognitive decline. Conclusion Across conditions, CPV reliably reflects cognitive status and predicts cognitive deterioration. CP alterations signify disturbances in CSF dynamics, neuroinflammatory activity, and protein clearance, positioning CPV as a promising transdiagnostic biomarker. Future longitudinal and multimodal studies are needed to clarify causal mechanisms and evaluate its clinical utility in diagnosis, prognosis, and therapeutic monitoring.