Commentary|Articles|January 16, 2026

Applied Clinical Trials

  • Applied Clinical Trials-02-01-2026
  • Volume 35
  • Issue 1

Women as the Missing Voice in Parkinson’s Disease

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As Parkinson’s disease cases surge worldwide, growing evidence gaps around women’s biology, care access, and outcomes are driving new data-driven and digital strategies to advance sex-specific research and precision medicine.

Parkinson’s disease by the numbers

  • 11.77 million people worldwide were living with Parkinson’s disease in 2021
  • Global prevalence is projected to more than double by 2050, reaching ~25.2 million people
  • Age-standardized prevalence stands at 138.63 per 100,000, with age as the dominant risk factor
  • Women remain underrepresented in PD research despite evidence of distinct symptoms and treatment responses
  • Initiatives like GEM-PD are building large, sex-specific datasets to close evidence gaps

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms (tremor, bradykinesia, rigidity) and a broad spectrum of non-motor features. PD is the fastest-growing and second largest neurological condition worldwide.1 In 2021, 11.77 million people worldwide had PD. Age-standardized rates of incidence, prevalence, and DALYs (Disability-Adjusted Life Years) increased to 15.63/100,000, 138.63/100,000, and 89.59/100,000.2 Modeling studies project that PD incidence will more than double by 2050, reaching approximately 25.2 million people globally, driven primarily by population aging and growth.1 Age remains the dominant risk factor, with incidence and prevalence increasing sharply in older age groups. Although PD has historically been reported as more common in men, the disease’s prevalence and burden in women remains substantial and under-characterized in clinical research.3

Women and PD: Advancing sex-specific evidence to improve clinical outcomes

Despite increasing recognition of PD’s global burden, systematic inclusion of sex-specific analyses in epidemiological studies, clinical trials, and translational research remains limited.4 For example, a recent study5 analyzing data from over 10,000 people with PD reported higher prevalence of dyskinesia in females than males. This gap limits the understanding of sex-based differences in disease expression, progression, and therapeutic response, thereby limiting precision medicine.

Beyond biological differences, gender-related factors significantly shape the lived experience of women with PD. Women encounter greater barriers to timely diagnosis, reduced access to specialist care, fewer social and familial supports. Evidence6 suggests that women with PD are less likely to receive informal caregiving support from partners contributing to increased psychological burden and reduced capacity for self-care. As disease progresses, these challenges are compounded by higher rates of anxiety, depression and psychological distress which are consistently associated with poorer quality of life outcomes in women. Together, these factors highlight the need to address both biological sex and gender-related determinants to meaningfully improve outcomes for women with PD.4,6

The Critical Path institute, a nonprofit organization whose mission is to lead collaborations that accelerate drug development, held its latest flagship Global Impact Conference in Washington DC in September 2025. The conference featured cross-sector networking, dynamic discussions, and real-world examples of how public-private partnerships can drive the transformation of data into actionable and clinically meaningful knowledge across a range of diseases of high unmet need, like PD. This necessary approach was illustrated in the Global Evidence in Medicine session that brought together interdisciplinary stakeholders to address these gaps and deficiencies and advocate for systematic inclusion of women in PD research.

Current evidence on sex differences in PD

Epidemiological studies consistently indicate that men are more frequently diagnosed with PD than women.6 However, women often exhibit distinct symptom profiles, including higher prevalence of symptoms such as depression, anxiety, and sleep disturbances.7 These differences are not yet fully understood because of the scarcity of robust sex-stratified data from large cohorts. Furthermore, women may experience distinct trajectories in disease progression and response to treatment, including deep brain simulation,8 approved symptomatic therapies and medical device treatment.6

Hormones such as estrogen have been hypothesized to exert neuroprotective effects, potentially influencing PD risk and progression. Yet, the mechanisms and clinical relevance of hormonal influences on PD remain unresolved and under-investigated due to a lack of adequately powered studies focusing on female neurobiology in PD. Investigations of genetic forms of PD are illuminating sex-specific differences with underlying biological differences. Emerging research on sex-specific gene expression and molecular pathways may further explain biological determinants of PD heterogeneity.

Digital health technologies in PD

The rise of digital health technologies (DHTs) has introduced new opportunities for PD assessment, monitoring, and research.9 These technologies offer objective, continuous, real-world data that can complement traditional clinical measures and potentially uncover often-overlooked patterns and charateristics.10 Such technologies hold promise for early detection and improved diagnosis,11 an area of need for women with PD.

Digital measures and digital biomarkers

Wearable sensors and smartphone applications are increasingly being used for quantifying motor and non-motor features of PD.12 These tools can generate digital biomarkers, quantifiable physiological and behavioral data that correlate with disease status and progression.13 For example, continuous mobility monitoring using accelerometers can produce real-world measures that are moderately correlated with standard clinical ratings and show greater sensitivity to change over time than traditional scales.14 A range of measures related to gait, posture, and daily activities have been investigated as potential digital measures, particularly for tracking early PD progression.15

Digital twins and advanced modeling

The concept of digital twins—computational models that simulate individual patients’ physiology and disease trajectories—is emerging in clinical research.16 While still nascent, digital twin frameworks aim to integrate diverse data streams (clinical, sensor, genomic, environmental) to enable personalized disease modeling, prognostication, and therapy optimization.10 To date, applications of digital twins in PD remain limited though examples are emerging across neurological diseases. Digital twin models could support sex-specific predictions of PD disease onset and progression, thereby enhancing precision medicine approaches.

Real-world data integration

Real-world data (RWD) from electronic health records, linked claims datasets, and patient-generated health data can provide large-scale longitudinal insights into PD care patterns and outcomes. Integration of real-world evidence with digital measures facilitates comprehensive phenotyping and expands the evidence base beyond traditional trial populations. These data sources are particularly valuable for examining sex differences in real-life settings and across heterogeneous patient populations.

While digital health technologies hold significant promise, challenges remain in standardization, validation, and regulatory acceptance. Harmonizing digital measure definitions and ensuring analytical and clinical validation are crucial for translating these measures into clinical and regulatory decision-making frameworks.

The GEM-PD initiative

The Global Evidence in Medicine for Parkinson’s disease (GEM-PD) initiative was launched by C-Path to focus on closing the gender gap in PD research and care through a comprehensive approach that leverages patient voices, data science, digital health technologies, and regulatory science. Objectives of GEM-PD include:

  • Enhancing data representation: GEM-PD’s database includes one of the largest curated collections of data from women with PD, enabling sex-specific analyses and biomarker discovery.
  • High-quality evidence generation: The initiative aims to identify and validate sex-specific biomarkers and clinical endpoints by integrating clinical, digital, and real-world data.
  • Informing clinical and regulatory frameworks: GEM-PD seeks to influence trial design, incorporating sex-specific hypotheses and outcomes to facilitate inclusive evidence generation.
  • Promoting precision medicine: By leveraging insights from sex-specific biology, GEM-PD strives to tailor therapies and improve outcomes for women with PD.
  • Patient-centricity advocacy: Patient advocates and clinicians with lived experience highlighting the practical and emotional impact of research gaps on women’s daily lives. Their narratives emphasize the importance of research that reflects patient experiences, addresses disparities in care access, and prioritizes patient-reported outcomes.

Challenges and future directions

Despite progress, women remain underrepresented in PD clinical trials, and validated sex-specific biomarkers are limited. A recent exploratory clinical trial investigating the potential of a repurposed therapy targeting neuroinflammation reported sex-specific differences as a function of treatment17 suggesting a potential biological basis for continued investigations. Integrating DHTs and RWD into formal research frameworks is promising but requires overcoming methodological and regulatory hurdles. Future efforts should prioritize inclusive recruitment strategies, large-scale longitudinal cohorts, and interdisciplinary collaborations. Funding mechanisms and policy incentives that mandate sex-inclusive research will be critical for sustainable progress. The GEM-PD initiative offers a strategic roadmap for addressing these gaps by leveraging DHTs, large-scale data integration, and collaborative science. Closing the gender gap in PD research is essential not only for equity but also for advancing precision medicine that benefits all people living with PD.

Authors

Bola Grace, PhD, MBA, Professor of Practice, University College London; Ragasudha Botta, MBBS, PhD, MMSc in Clinical Investigation from Harvard Medical School, Massachusetts General Hospital; and Diane Stephenson, PhD; Vice President Neurology, Critical Path Institute.

Acknowledgements

The authors would like to acknowledge Critical Path Institute, Critical Path for Parkinson’s consortium, Dr. Carly Tanner (UCSF), Dr. Catherine Kopil (Michael J Fox Foundation), Dr. Sonia Mathur (PD Avengers, Unshakable PD) and Dr. Derek Hill (UCL, Panoramic Digital Health) for their insights and perspectives on women’s voices in PD.

References

1. Su D, Cui Y, He C, Yin P, Bai R, Zhu J, et al. Projections for prevalence of Parkinson’s disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021. BMJ [Internet]. 2025 Mar 5;388. Available from: https://www.bmj.com/content/388/bmj-2024-080952

2. Luo Y, Qiao L, Li M, Wen X, Zhang W, Li X. Global, regional, national epidemiology and trends of Parkinson’s disease from 1990 to 2021: findings from the Global Burden of Disease Study 2021. Front Aging Neurosci [Internet]. 2024 Jan 10;16:1498756. Available from: https://www.healthdata.org/researchanalysis/gbd

3. Tsai CC, Tao B, Lin V, Lo J, Brahmbhatt S, Kalo C, et al. Representational Disparities in the Enrollment of Parkinson’s Disease Clinical Trials. Mov Disord Clin Pract [Internet]. 2025 Jun 1;12(6):878–81. Available from: /doi/pdf/10.1002/mdc3.70009

4. Castro-Aldrete L, Huc M, Domingos J, Vaudano E, Klietz M, Trenkwalder C, et al. Using a sex- and gender-informed lens to enhance care in Parkinson’s disease. Nature Medicine 2025 31:2 [Internet]. 2025 Jan 3;31(2):367–9. Available from: https://www.nature.com/articles/s41591-024-03363-2

5. Bentall LM, Parr-Brownlie LC. Sexual Dimorphism in Levodopa-Induced Dyskinesia Following Parkinson’s Disease: Uncharted Territory. European Journal of Neuroscience [Internet]. 2025 May 1;61(9):e70144. Available from: /doi/pdf/10.1111/ejn.70144

6. Cattaneo C, Pagonabarraga J. Sex Differences in Parkinson’s Disease: A Narrative Review. Neurology and Therapy 2024 14:1 [Internet]. 2024 Dec 4;14(1):57–70. Available from: https://link.springer.com/article/10.1007/s40120-024-00687-6

7. Subramanian I, Mathur S, Oosterbaan A, Flanagan R, Keener AM, Moro E. Unmet Needs of Women Living with Parkinson’s Disease: Gaps and Controversies. Movement Disorders [Internet]. 2022 Mar 1;37(3):444–55. Available from: /doi/pdf/10.1002/mds.28921

8. Jost ST, Strobel L, Rizos A, Loehrer PA, Ashkan K, Evans J, et al. Gender gap in deep brain stimulation for Parkinson’s disease. npj Parkinson’s Disease 2022 8:1 [Internet]. 2022 Apr 20;8(1):47-. Available from: https://www.nature.com/articles/s41531-022-00305-y

9. Khanna A, Beck J, Poston K, Schwarzschild MA, Jones GB. The potential of distributed diagnostics for the early detection of Parkinson’s disease. J Parkinsons Dis [Internet]. 2025 May 1;15(3):646–53. Available from: https://journals.sagepub.com/doi/10.1177/1877718X251336118?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed

10. Grace B, Wise LA, Nieroda M, Egbunike J, Usman NO. Digital health technologies to transform women’s health innovation and inclusive research. BMJ [Internet]. 2025 Oct 10 [cited 2025 Oct 21];391:e085682. Available from: https://www.bmj.com/content/391/bmj-2025-085682

11. Borges do Nascimento IJ, Abdulazeem HM, Weerasekara I, Marquez J, Vasanthan LT, Deeken G, et al. Transforming women’s health, empowerment, and gender equality with digital health: evidence-based policy and practice. Lancet Digit Health [Internet]. 2025 Jun 1;7(6):100858. Available from: https://www.thelancet.com/action/showFullText?pii=S2589750025000226

12. Virameteekul S, Shin C, Hirczy SS, Sarva H, Paul SS, Maetzler W, et al. Assessing Digital Health Technologies for Outcome Measurement in Parkinson’s Disease Drug Trials: A Systematic Review. Movement Disorders [Internet]. 2025; Available from: /doi/pdf/10.1002/mds.70097

13. Grace B. Accelerating women’s health research and innovation. The Lancet Obstetrics, Gynaecology, & Women’s Health [Internet]. 2025 Jul 24; Available from: https://doi.org/10.1016/S3050-5038

14. Rábano-Suárez P, del Campo N, Benatru I, Moreau C, Desjardins C, Sánchez-Ferro Á, et al. Digital Outcomes as Biomarkers of Disease Progression in Early Parkinson’s Disease: A Systematic Review. Movement Disorders [Internet]. 2025 Feb 1 [cited 2025 Dec 23];40(2):184–203. Available from: /doi/pdf/10.1002/mds.30056

15. Sun YM, Wang ZY, Liang YY, Hao CW, Shi CH. Digital biomarkers for precision diagnosis and monitoring in Parkinson’s disease. npj Digital Medicine 2024 7:1 [Internet]. 2024 Aug 21;7(1):218-. Available from: https://www.nature.com/articles/s41746-024-01217-2

16. Torresi G, Verna, Roberto. Digital twins: A new paradigm for innovation in clinical research and medical affairs DIGITAL TWIN: THEORETICAL FOUNDATIONS, MODELS, AND APPLICATION ARCHITECTURE IN HEALTHCARE Conceptual Origins and Operating Principles. Malays J Pathol. 2025;47(3):355–68.

17. Greenland JC, Dresser K, Cutting E, Donegan R, Bond S, Crisp SJ, et al. Azathioprine for the treatment of early Parkinson’s disease (AZA-PD): a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial. Lancet Neurol [Internet]. 2026 Jan 1;25(1):39–49. Available from: https://www.thelancet.com/action/showFullText?pii=S1474442225003862

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