Sex differences in alpha-synucleinopathies: a systematic review

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Abstract

Background

Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach.

Methods

In this systematic review, studies investigating sex and gender differences in alpha-synucleinopathies (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson’s Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) from 2012 to 2022 were identified using electronic database searches of PubMed, Embase and Ovid.

Results

One hundred sixty-two studies were included; 5 RBD, 6 MSA, 20 DLB and 131 PD studies. Overall, there is conclusive evidence to suggest sex-and gender-specific manifestation in demographics, biomarkers, genetics, clinical features, interventions, and quality of life in alpha-synucleinopathies. Only limited data exists on the effects of distinct sex hormones, with majority of studies concentrating on estrogen and its speculated neuroprotective effects.

Conclusion

Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics.

Related collections

Most cited references 276

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David Moher, Alessandro Liberati, Jennifer Tetzlaff … (2009)

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Is Open Access

AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both

Beverley Shea, Barnaby Reeves, George Wells … (2017)

The number of published systematic reviews of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions. Systematic reviews are subject to a range of biases and increasingly include non-randomised studies of interventions. It is important that users can distinguish high quality reviews. Many instruments have been designed to evaluate different aspects of reviews, but there are few comprehensive critical appraisal instruments. AMSTAR was developed to evaluate systematic reviews of randomised trials. In this paper, we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic reviews, including those based on non-randomised studies of healthcare interventions.

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Alpha-synuclein in Lewy bodies.

Maria Spillantini, Marie Schmidt, Virginia Virginia M.-Y. Lee … (1997)

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Author and article information

Contributors

Kausar Raheel: URI : https://loop.frontiersin.org/people/2326804/overview

Gemma Deegan: URI : https://loop.frontiersin.org/people/2299952/overview

Irene Di Giulio: URI : https://loop.frontiersin.org/people/488771/overview

Diana Cash: URI : https://loop.frontiersin.org/people/311879/overview

Katarina Ilic: URI : https://loop.frontiersin.org/people/639701/overview

Valentina Gnoni: URI : https://loop.frontiersin.org/people/1622959/overview

K. Ray Chaudhuri: URI : https://loop.frontiersin.org/people/444967/overview

Panagis Drakatos: URI : https://loop.frontiersin.org/people/1850871/overview

Rosalyn Moran: URI : https://loop.frontiersin.org/people/13473/overview

Ivana Rosenzweig: URI : https://loop.frontiersin.org/people/307199/overview

Journal

Journal ID (nlm-ta): Front Neurol

Journal ID (iso-abbrev): Front Neurol

Journal ID (publisher-id): Front. Neurol.

Title: Frontiers in Neurology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2295

Publication date (Electronic): 20 July 2023

Publication date Collection: 2023

Volume: 14

Electronic Location Identifier: 1204104

Affiliations

[1] ¹Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London , London, United Kingdom

[2] ²BRAIN, Imaging Centre, CNS, King’s College London , London, United Kingdom

[3] ³School of Basic and Medical Biosciences, Faculty of Life Science and Medicine, King’s College London , London, United Kingdom

[4] ⁴Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London , London, United Kingdom

[5] ⁵Center for Neurodegenerative Diseases and the Aging Brain, University of Bari Aldo Moro , Lecce, Italy

[6] ⁶Movement Disorders Unit, King’s College Hospital and Department of Clinical and Basic Neurosciences, Institute of Psychiatry, Psychology and Neuroscience and Parkinson Foundation Centre of Excellence, King’s College London , London, United Kingdom

[7] ⁷Sleep Disorders Centre, Guy’s and St Thomas’ NHS Foundation Trust , London, United Kingdom

Author notes

Edited by: Satvinder Kaur, Harvard Medical School, United States

Reviewed by: Roberta Marongiu, Cornell University, United States; Jorge Hernandez-Vara, Hospital Universitari Vall D¨Hebron, Spain

*Correspondence: Ivana Rosenzweig, ivana.1.rosenzweig@ 123456kcl.ac.uk

^†These authors share first authorship

Article

DOI: 10.3389/fneur.2023.1204104

PMC ID: 10398394

PubMed ID: 37545736

SO-VID: bdeee296-ddcc-4483-9fc9-a3e448ff5190

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 11 April 2023

Date accepted : 13 June 2023

Page count

Figures: 3, Tables: 6, Equations: 0, References: 278, Pages: 30, Words: 22935

Custom metadata

section-at-acceptance Sleep Disorders

ScienceOpen disciplines: Neurology

Keywords: alpha-synucleinopathies,sex differences,estrogen,parkinson’s disease,dementia with lewy bodies

Data availability:

ScienceOpen disciplines: Neurology

Keywords: alpha-synucleinopathies, sex differences, estrogen, parkinson’s disease, dementia with lewy bodies

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Sex differences in alpha-synucleinopathies: a systematic review

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Abstract

Background

Methods

Results

Conclusion

Related collections

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Most cited references 276

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both

Alpha-synuclein in Lewy bodies.

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Cited by 10

Most referenced authors 4,335