Abstract
BackgroundThe presence of rapid eye movement sleep behavior disorder (RBD) contributes to increase cognitive impairment and brain atrophy in Parkinson’s disease (PD), but the impact of sex is unclear. We aimed to investigate sex differences in cognition and brain atrophy in PD patients with and without probable RBD (pRBD).MethodsMagnetic resonance imaging and cognition data were obtained for 274 participants from the Parkinson's Progression Marker Initiative database: 79 PD with pRBD (PD-pRBD; male/female, 54/25), 126 PD without pRBD (PD-non pRBD; male/female, 73/53), and 69 healthy controls (male/female, 40/29). FreeSurfer was used to obtain volumetric and cortical thickness data.ResultsMales showed greater global cortical and subcortical gray matter atrophy than females in the PD-pRBD group. Significant group-by-sex interactions were found in the pallidum. Structures showing a within-group sex effect in the deep gray matter differed, with significant volume reductions for males in one structure in in PD-non pRBD (brainstem), and three in PD-pRBD (caudate, pallidum and brainstem). Significant group-by-sex interactions were found in Montreal Cognitive Assessment (MoCA) and Symbol Digits Modalities Test (SDMT). Males performed worse than females in MoCA, phonemic fluency and SDMT in the PD-pRBD group.ConclusionMale sex is related to increased cognitive impairment and subcortical atrophy in de novo PD-pRBD. Accordingly, we suggest that sex differences are relevant and should be considered in future clinical and translational research.
Highlights
There is significant cumulative evidence for Alzheimer’s disease [1] and Parkinson’s disease (PD) [2, 3] that susceptibility to regional brain atrophy and cognitive impairment differs by sex
There was a significant group-by-sex interaction in the RBD Screening Questionnaire (RBDSQ) score (F = 4.749, p = 0.009), with post hoc analyses showing that males in the PD-probable RBD (pRBD) group had more severe motor and rapid eye movement sleep behavior disorder (RBD) symptoms than females in this group
Both groups of PD males performed worse than HC males in Montreal Cognitive Assessment (MoCA) and Symbol Digits Modalities Test (SDMT), PD with pRBD (PD-pRBD) males performed worse than PD-non pRBD males in SDMT (Fig. 1 and Supplementary Table 3)
Summary
There is significant cumulative evidence for Alzheimer’s disease [1] and Parkinson’s disease (PD) [2, 3] that susceptibility to regional brain atrophy and cognitive impairment differs by sex. These between-sex differences on brain degeneration have implications for implementing prevention, diagnosis, and treatment strategies in the context of precision medicine. Results Males showed greater global cortical and subcortical gray matter atrophy than females in the PD-pRBD group. Structures showing a within-group sex effect in the deep gray matter differed, with significant volume reductions for males in one structure in in PD-non pRBD (brainstem), and three in PD-pRBD (caudate, pallidum and brainstem). We suggest that sex differences are relevant and should be considered in future clinical and translational research
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