Basal forebrain volume predicts disease conversion in prodromal synucleinopathy

Background: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The basal forebrain (BF), a key cholinergic structure, is a site of known pathology in later stages of Lewy body disorders. Although bilateral BF atrophy has been linked to cognitive decline in iRBD, its potential role in predicting phenoconversion to PD and DLB remains unclear. Objectives: The aims were to examine BF gray matter volume differences between iRBD patients and healthy controls, and evaluate their utility as predictors of phenoconversion to PD or DLB. Exploratory post hoc analyses were also conducted to explore the lateral-specific effects of BF atrophy in relation to disease conversion. Methods: We assessed 41 participants with polysomnography-confirmed iRBD and 38 healthy controls using baseline T1-weighted magnetic resonance imaging (MRI) and longitudinal clinical assessments. Gray matter volumes of the left and right BF were compared between groups. Cox proportional hazards models examined baseline BF volumes as predictors of phenoconversion risk to PD and DLB. Results: Although no significant group differences in BF volume were found, lower BF volume was associated with poorer global cognition in iRBD. Bilateral BF atrophy predicted increased risk of phenoconversion to either PD or DLB. An exploratory post hoc analysis revealed that left BF atrophy specifically predicted conversion to DLB, whereas right BF volume did not. Conclusion: Bilateral BF atrophy may represent an early biomarker of phenoconversion in iRBD, with left-sided atrophy potentially indicating increased risk for DLB. These findings highlight the prognostic value of BF degeneration in prodromal synucleinopathies.