Sex differences in brain atrophy and cognitive impairment in Parkinson’s disease patients with and without probable rapid eye movement sleep behavior disorder

Abstract

Background The 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). Methods Magnetic 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. Results Males 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. Conclusion Male 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.

The structural changes of gray matter in Parkinson disease patients with mild cognitive impairments

“…The increased GMV in the putamen in the PD patients with NCI was unexpected but was consistent with the previous studies [ 57 , 58 ], and may support the concept of striatum compensation in PD. The putamen is the striatal nucleus mainly linked with motor performance.…”

Neuroimaging of rapid eye movement sleep behavior disorder and its relation to Parkinson's disease

“…Male sex is risk factor for both iRBD and PD incidence, with around 80% of iRBD patients being male (Fernández‐Arcos et al, 2016) and the incidence of parkinsonism in males:females is 2:1 (Baldereschi et al, 2000). Oltra and colleagues (2022) explored the sex differences in disease incidence by stratifying the PPMI cohort. The authors found that male PD patients with RBD had greater global cortical atrophy and deep gray matter loss in the caudate, pallidum, and brainstem regions compared to female PD patients with RBD.…”

Task-specific effects of biological sex and sex hormones on object recognition memories in a 6-hydroxydopamine-lesion model of Parkinson’s disease in adult male and female rats

“…Meta analyses identify male sex as a risk factor for cognitive and memory dysfunction in PD[34–36]. Male patients are also more likely to develop cognitive and memory deficits early, to experience a more rapid course of cognitive decline and to be at greater risk for cognitive and memory deficits to progress to PDD[34, 37, 38]. These sex-specific features raise critical questions about the impacts of gonadal steroid hormones on cognition and memory in PD.…”

“…For example, metaanalyses have identified male sex as conferring risk for cognitive and memory dysfunction in PD [34][35][36]. Clinical studies have also identified poorer spatial cognition, lower scores on tests of executive function, slower processing speed and reduced initiative in male compared to female patients as well as a greater likelihood for these deficits in males to progress from absent to mild and from mild to PDD [34,37,38]. These patterns suggest potentially important roles for circulating gonadal hormones in sex-specifically influencing cognition and memory in PD.…”