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      Parkinson’s Disease in Women and Men: What’s the Difference?

      review-article
      , , *
      Journal of Parkinson's Disease
      IOS Press
      Parkinson’s disease, sex, gender, risk factors, estrogens, signs and symptoms, dopaminergic neurons, neuroinflammation, oxidative stress

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          Abstract

          Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson’s disease (PD). Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. Altogether, sex-related differences in PD support the idea that disease development might involve distinct pathogenic mechanisms (or the same mechanism but in a different way) in male and female patients. This review summarizes the most recent knowledge concerning differences between women and men in PD clinical features, risk factors, response to treatments and mechanisms underlying the disease pathophysiology. Unraveling how the pathology differently affect the two sexes might allow the development of tailored interventions and the design of innovative programs that meet the distinct needs of men and women, improving patient care.

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          Most cited references136

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          Parkinson disease: from pathology to molecular disease mechanisms.

          Parkinson disease (PD) is a complex neurodegenerative disorder with both motor and nonmotor symptoms owing to a spreading process of neuronal loss in the brain. At present, only symptomatic treatment exists and nothing can be done to halt the degenerative process, as its cause remains unclear. Risk factors such as aging, genetic susceptibility, and environmental factors all play a role in the onset of the pathogenic process but how these interlink to cause neuronal loss is not known. There have been major advances in the understanding of mechanisms that contribute to nigral dopaminergic cell death, including mitochondrial dysfunction, oxidative stress, altered protein handling, and inflammation. However, it is not known if the same processes are responsible for neuronal loss in nondopaminergic brain regions. Many of the known mechanisms of cell death are mirrored in toxin-based models of PD, but neuronal loss is rapid and not progressive and limited to dopaminergic cells, and drugs that protect against toxin-induced cell death have not translated into neuroprotective therapies in humans. Gene mutations identified in rare familial forms of PD encode proteins whose functions overlap widely with the known molecular pathways in sporadic disease and these have again expanded our knowledge of the neurodegenerative process but again have so far failed to yield effective models of sporadic disease when translated into animals. We seem to be missing some key parts of the jigsaw, the trigger event starting many years earlier in the disease process, and what we are looking at now is merely part of a downstream process that is the end stage of neuronal death. Copyright © 2013 Elsevier Inc. All rights reserved.
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            The Incidence of Parkinson's Disease: A Systematic Review and Meta-Analysis

            Background: Parkinson's disease (PD) is a common neurodegenerative disorder. Epidemiological studies on the incidence of PD are important to better understand the risk factors for PD and determine the condition's natural history. Objective: This systematic review and meta-analysis examine the incidence of PD and its variation by age and gender. Methods: We searched MEDLINE and EMBASE for epidemiologic studies of PD from 2001 to 2014, as a previously published systematic review included studies published until 2001. Data were analyzed separately for age group and gender, and meta-regression was used to determine whether a significant difference was present between groups. Results: Twenty-seven studies were included in the analysis. Meta-analysis of international studies showed rising incidence with age in both men and women. Significant heterogeneity was observed in the 80+ group, which may be explained by methodological differences between studies. While males had a higher incidence of PD in all age groups, this difference was only statistically significant for those in the age range 60-69 and 70-79 (p < 0.05). Conclusion: PD incidence generally increases with age, although it may stabilize in those who are 80+.
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              Sex-Specific Features of Microglia from Adult Mice

              Summary Sex has a role in the incidence and outcome of neurological illnesses, also influencing the response to treatments. Neuroinflammation is involved in the onset and progression of several neurological diseases, and the fact that estrogens have anti-inflammatory activity suggests that these hormones may be a determinant in the sex-dependent manifestation of brain pathologies. We describe significant differences in the transcriptome of adult male and female microglia, possibly originating from perinatal exposure to sex steroids. Microglia isolated from adult brains maintain the sex-specific features when put in culture or transplanted in the brain of the opposite sex. Female microglia are neuroprotective because they restrict the damage caused by acute focal cerebral ischemia. This study therefore provides insight into a distinct perspective on the mechanisms underscoring a sexual bias in the susceptibility to brain diseases.
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                Author and article information

                Journal
                J Parkinsons Dis
                J Parkinsons Dis
                JPD
                Journal of Parkinson's Disease
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                1877-7171
                1877-718X
                04 July 2019
                30 July 2019
                2019
                : 9
                : 3
                : 501-515
                Affiliations
                [1] Laboratory of Cellular and Molecular Neurobiology , IRCCS Mondino Foundation, Pavia, Italy
                Author notes
                [* ]Correspondence to: Dr. Fabio Blandini, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy. Tel.: +39 0382 380416; E-mail: fabio.blandini@ 123456mondino.it .
                Article
                JPD191683
                10.3233/JPD-191683
                6700650
                31282427
                6b940601-f9c5-4093-b5b7-2eccc3aa0ce0
                © 2019 – IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 May 2019
                Categories
                Review

                parkinson’s disease,sex,gender,risk factors,estrogens,signs and symptoms,dopaminergic neurons,neuroinflammation,oxidative stress

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