Sex Differences in Brain and Cognition in de novo Parkinson's Disease

Abstract

Background and Objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson's disease (PD) patients.Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males: 78 females) and 69 healthy controls (40 males: 29 females) were obtained from the PPMI dataset.Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function.Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD.

Efficacy of repetitive transcranial magnetic stimulation in Parkinson's disease: A systematic review and meta-analysis of randomised controlled trials

“…Moreover, the sex difference was not considered a comparable factor in our meta-analysis, while Oltra et al (2022) reported that the sex effect may significantly affect cognitive impairment in patients with PD. 69 Sex differences may require attention in future studies of cognitive assessment in patients with PD.…”

“…Moreover, the sex difference was not considered a comparable factor in our meta-analysis, while Oltra et al (2022) reported that the sex effect may significantly affect cognitive impairment in patients with PD. 69 Sex differences may require attention in future studies of cognitive assessment in patients with PD. Meanwhile, some studies pointed out that other factors like diabetes mellitus could affect the progression of PD and its motor and non-motor symptoms, especially the cognition symptoms, 46 , 70 , 71 , 72 which may affect the efficacy of rTMS intervention and the result of this meta-analysis.…”

Sex differences in clinical cognitive impairment with Lewy bodies: a Chinese multicenter study

“…In the prodromal and dementia stages of LBD, patients show different sex predominance in core clinical features. Previous studies in patients with PD and PDD showed that RBD was more common in men [ 12 , 37 ], and its presence and severity were associated with decreased cerebrospinal fluid (CSF) alpha-synuclein level [ 38 , 39 ]. Although Yu et al [ 39 ] showed that omen had lower CSF alpha-synuclein levels (1429 ± 164 vs 1831 ± 60, p = 0.02) than men, and only one longitudinal study [ 40 ] revealed a significant correlation between estimated changes in alpha-synuclein level and RBD-SQ scores ( p = 0.001, data not available), we still do not know how sex influences occurrence of RBD by influencing alpha-synuclein levels.…”

The X factor in neurodegeneration

“…Parkinson’s disease (PD) has a higher incidence in males than females with a ratio of 2:1 ( Oltra et al, 2022 ; Shulman and Bhat, 2006 ), and progression of degeneration of the nigrostriatal system is thought to be worse in men ( Jurado-Coronel et al, 2018 ). Men with PD have more severe cognitive impairment, namely executive function and processing speed as measured by the Montreal Cognitive Assessment and the Symbol Digits Modalities Test, respectively ( Oltra et al, 2022 ; Oltra et al, 2021 ; Reekes et al, 2020 ). Also, PD males have worse cortical thinning in postcentral and precentral regions and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem compared with PD females ( Oltra et al, 2022 ; Oltra et al, 2021 ).…”

“…Men with PD have more severe cognitive impairment, namely executive function and processing speed as measured by the Montreal Cognitive Assessment and the Symbol Digits Modalities Test, respectively ( Oltra et al, 2022 ; Oltra et al, 2021 ; Reekes et al, 2020 ). Also, PD males have worse cortical thinning in postcentral and precentral regions and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem compared with PD females ( Oltra et al, 2022 ; Oltra et al, 2021 ). Whether testosterone deficiency in aging males or exposure to pesticides that act via estrogen-blocking properties can predispose to PD is a subject of speculation ( Brenner, 2012 ; Okun et al, 2004 ; Okun et al, 2006 ; Okun et al, 2002 ).…”