Retrospective cross-sectional study reveals distinct limbic atrophy across prodromal Parkinson's disease phenotypes, indicating extensive network degeneration in hyposmia-related groups.
Key Points
To investigate limbic structural alterations and network covariance patterns across distinct prodromal Parkinson's disease phenotypes characterized by REM sleep behavior disorder and hyposmia.
Retrospective cross-sectional analysis of 315 age- and sex-matched participants (mean age 68.34 years; n = 63 per group: healthy controls, isolated REM sleep behavior disorder, isolated hyposmia, combined phenotype, and untreated Parkinson's disease).
Extracted 34 limbic region volumes from 3T T1-weighted MRI using FreeSurfer and ScLimbic, normalized to intracranial volume, and harmonized with ComBat.
Assessed volumetric differences and linear trends across phenotypes using one-way ANCOVA and structural covariance mapping adjusted for false discovery rate (FDR p < 0.05).
Significant volumetric reductions occurred across groups in the bilateral insula, bilateral orbitofrontal cortex, and left parahippocampal gyrus after FDR correction.
The strongest negative linear trends across phenotype orderings emerged in the orbitofrontal cortex (left β = −0.319 to −0.287; right β = −0.297 to −0.266) and left parahippocampal gyrus (β = −0.297 to −0.268).
Within-group covariance maps demonstrated that hyposmia-associated phenotypes feature more pronounced limbic alterations in olfactory and Papez circuit networks compared to isolated REM sleep behavior disorder.