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Sex differences in Parkinson's disease presentation and progression.

ABSTRACT: INTRODUCTION:Females have a reduced risk of Parkinson's disease (PD). However, it is unclear if sex is a prognostic factor. We aimed to examine differences in presentation, physician- and patient-reported PD outcomes, and progression by sex in a large clinical cohort. METHODS:This study was a secondary analysis of a cohort of PD patients seen at a tertiary care center. Sociodemographic and clinical characteristics, treatment, care timing, and outcomes were examined by sex. Sex differences in progression of impairment, disability, and health-related quality of life (HRQoL) were tested with five-year piecewise linear mixed-effects models. A mediation analysis assessed drivers of sex differences. RESULTS:The study included 914 males and 549 females. Females had significantly less social support, more psychological distress, and worse self-reported (but not physician-reported) disability and HRQoL at initial PD care visits, compared to males. Addressing anxiety symptoms may attenuate this difference. PD progression sex differences were minimal. CONCLUSION:PD progression does not differ by sex, yet patient-reported measures of disease severity are worse in females than males. To attenuate this sex difference in disease experience, psychological distress screening and management, particularly targeting females, should be implemented as part of PD clinical care.

SUBMITTER: Abraham DS

PROVIDER: S-EPMC6982644 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Sex differences in Parkinson's disease presentation and progression.

Abraham Danielle S DS Gruber-Baldini Ann L AL Magder Laurence S LS McArdle Patrick F PF Tom Sarah E SE Barr Erik E Schrader Katrina K Shulman Lisa M LM

Parkinsonism & related disorders 20191023

<h4>Introduction</h4>Females have a reduced risk of Parkinson's disease (PD). However, it is unclear if sex is a prognostic factor. We aimed to examine differences in presentation, physician- and patient-reported PD outcomes, and progression by sex in a large clinical cohort.<h4>Methods</h4>This study was a secondary analysis of a cohort of PD patients seen at a tertiary care center. Sociodemographic and clinical characteristics, treatment, care timing, and outcomes were examined by sex. Sex dif ...[more]

PMID: 31677455

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Project description:Alzheimer's disease (AD) is the leading cause of dementia; however, men and women face differential AD prevalence, presentation, and progression risks. Characterizing metabolomic profiles during AD progression is fundamental to understand the metabolic disruptions and the biological pathways involved. However, outstanding questions remain of whether peripheral metabolic changes occur equally in men and women with AD. Here, we evaluated differential effects of metabolomic and brain volume associations between sexes. We used three cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI), evaluated 1,368 participants, two metabolomic platforms with 380 metabolites in total, and six brain segment volumes. Using dimension reduction techniques, we took advantage of the correlation structure of the brain volume phenotypes and the metabolite concentration values to reduce the number of tests while aggregating relevant biological structures. Using WGCNA, we aggregated modules of highly co-expressed metabolites. On the other hand, we used partial least squares regression-discriminant analysis (PLS-DA) to extract components of brain volumes that maximally co-vary with AD diagnosis as phenotypes. We tested for differences in effect sizes between sexes in the association between single metabolite and metabolite modules with the brain volume components. We found five metabolite modules and 125 single metabolites with significant differences between sexes. These results highlight a differential lipid disruption in AD progression between sexes. Men showed a greater negative association of phosphatidylcholines and sphingomyelins and a positive association of VLDL and large LDL with AD progression. In contrast, women showed a positive association of triglycerides in VLDL and small and medium LDL with AD progression. Explicitly identifying sex differences in metabolomics during AD progression can highlight particular metabolic disruptions in each sex. Our research study and strategy can lead to better-tailored studies and better-suited treatments that take sex differences into account.

Project description:Parkinson's disease is an age-related neurodegenerative disorder with a higher incidence in males than females. The causes for this sex difference are unknown. Genome-wide association studies (GWAS) have identified 90 Parkinson's disease risk loci, but the genetic studies have not found sex-specific differences in allele frequency on autosomal chromosomes or sex chromosomes. Genetic variants, however, could exert sex-specific effects on gene function and regulation of gene expression. To identify genetic loci that might have sex-specific effects, we studied pleiotropy between Parkinson's disease and sex-specific traits. Summary statistics from GWASs were acquired from large-scale consortia for Parkinson's disease (n cases = 13 708; n controls = 95 282), age at menarche (n = 368 888 females) and age at menopause (n = 69 360 females). We applied the conditional/conjunctional false discovery rate (FDR) method to identify shared loci between Parkinson's disease and these sex-specific traits. Next, we investigated sex-specific gene expression differences in the superior frontal cortex of both neuropathologically healthy individuals and Parkinson's disease patients (n cases = 61; n controls = 23). To provide biological insights to the genetic pleiotropy, we performed sex-specific expression quantitative trait locus (eQTL) analysis and sex-specific age-related differential expression analysis for genes mapped to Parkinson's disease risk loci. Through conditional/conjunctional FDR analysis we found 11 loci shared between Parkinson's disease and the sex-specific traits age at menarche and age at menopause. Gene-set and pathway analysis of the genes mapped to these loci highlighted the importance of the immune response in determining an increased disease incidence in the male population. Moreover, we highlighted a total of nine genes whose expression or age-related expression in the human brain is influenced by genetic variants in a sex-specific manner. With these analyses we demonstrated that the lack of clear sex-specific differences in allele frequencies for Parkinson's disease loci does not exclude a genetic contribution to differences in disease incidence. Moreover, further studies are needed to elucidate the role that the candidate genes identified here could have in determining a higher incidence of Parkinson's disease in the male population.

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Sex differences in Parkinson's disease presentation and progression.

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Sex differences in Parkinson's disease presentation and progression.

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