Objective: To identify differences in the self-reported prodromal symptoms of male vs female persons with PD (PwPD) in the Fox Insight (FI) cohort.
Background: Early detection of PD may be crucial in effective disease modification. Prior studies have observed sex differences in PD symptoms1-4 that may extend to the prodromal stage,5-6 though studies often have limited sample size or a small proportion of female participants. This study investigates a large sample from the FI cohort to explore differences in prodromal symptoms between male and female PwPD, with the goal of adequate recognition in specific populations in this crucial early stage.
Method: FI is a longitudinal study including PwPD and people without PD that involves online questionnaires.7, 8 We administered a questionnaire to PwPD enrolled in FI that asked about the types of symptoms PwPD experienced prior to diagnosis. Differences in reporting frequencies between male and female PwPD were analyzed using chi-square tests.
Results: Overall, 5715 PwPD responded to the questionnaire, 2870 males and 2845 females. Male PwPD were older than female PwPD (p<0.05), though the difference was small (69.97 vs 68.98, d=0.11); there was no significant difference in PD duration at the time of questionnaire response. (Table 1). We observed [BE1] statistically significant differences (p<0.05) between male and female PwPD in several reported prodromal symptoms (Figure 1). Females were more likely to report constipation (35.1% vs 23.8%), shoulder pain (29.1% vs 19.2%), internal sense of shakiness (25.9% vs 18.5%), nervousness/anxiety (28.6% vs 22.6%), difficulty falling asleep (30.6% vs 21.0%). Males were more likely to report dream enactment (25.8% vs 15.0%), difficulty having sex (22.5% vs 13.0%), softer voice (27.3% vs 18.3%), decreased facial expression (20.2% vs 14.2%), hyposmia (41.1% vs 39.9%), and frequent nighttime urination (39.7 vs 34.4%).
Conclusion: Male and female PwPD report different prodromal symptoms, suggesting a need for sex-specific prodromal PD screening. Prodromal symptoms, such as dream enactment, and hyposmia, are reported more commonly by males, while less often recognized symptoms such as shoulder pain, internal sensation of shakiness, and anxiety are reported by women. Improving recognition of prodromal symptoms common in women could reduce diagnostic delay and improve access to early intervention and clinical trials.
Table 1- Demographics
Figure 1- Reported prodromal symptoms by PwPD
References: [1] Cattaneo, C., Pagonabarraga, J. Sex Differences in Parkinson’s Disease: A Narrative Review. Neurol Ther 14, 57–70 (2025). https://doi.org/10.1007/s40120-024-00687-6
[2] Bovenzi R, Conti M, De Franco V, Pierantozzi M, Schirinzi T, Cerroni R, Stefani A, Mercuri NB, Liguori C. Sex differences in Parkinson’s disease-related non motor symptoms: a focus on sleep problems. Acta Neurol Belg. 2024 Oct;124(5):1525-1534. doi: 10.1007/s13760-024-02535-8. Epub 2024 Apr 4. PMID: 38573491; PMCID: PMC11614980.
[3] Picillo M, LaFontant DE, Bressman S, Caspell-Garcia C, Coffey C, Cho HR, Burghardt EL, Dahodwala N, Saunders-Pullman R, Tanner CM, Amara AW; Parkinson’s Progression Markers Initiative. Sex-Related Longitudinal Change of Motor, Non-Motor, and Biological Features in Early Parkinson’s Disease. J Parkinsons Dis. 2022;12(1):421-436. doi: 10.3233/JPD-212892. PMID: 34744052; PMCID: PMC8842783.]
[4] Martinez-Martin P, Falup Pecurariu C, Odin P, van Hilten JJ, Antonini A, Rojo-Abuin JM, Borges V, Trenkwalder C, Aarsland D, Brooks DJ, Ray Chaudhuri K. Gender-related differences in the burden of non-motor symptoms in Parkinson’s disease. J Neurol. 2012 Aug;259(8):1639-47. doi: 10.1007/s00415-011-6392-3. Epub 2012 Jan 12. PMID: 22237822.
[5] Durcan, R., Wiblin, L., Lawson, R. A., Khoo, T. K., Yarnall, A. J., Duncan, G. W., Brooks, D. J., Pavese, N., & Burn, D. J. (2019). Prevalence and duration of non‐motor symptoms in prodromal Parkinson’s disease. European Journal of Neurology, 26(7), 979–985.
[6] K. Atterling Brolin, S. Waters, H. Chohan, B. Huxford, S. Meyer, L. Smith, A. Shahid, A. Kuri, J. Bestwick, R. Benabderrazik, R. Lathey, E. Pablo Fernandez, L. Pérez-Carbonell, C. Simonet, A. Schrag, A. Noyce. Sex differences in prodromal Parkinson’s disease (PD) [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/sex-differences-in-prodromal-parkinsons-disease-pd/.
[7] Smolensky L, Amondikar N, Crawford K, et al. Fox Insight collects online, longitudinal patient-reported outcomes and genetic data on Parkinson’s disease. Sci Data. 2020;7(1):67.
[8] Gottesman J, Karim Y, Forbes J, Kirsch L, Stagman K, Korell M, Tanner C. Fox Insight at 5 years – a cohort of 54,000 participants contributing longitudinal patient-reported outcome, genetic, and microbiome data relating to Parkinson’s disease. Sci Data. 2024 Jun 12;11(1):615.
To cite this abstract in AMA style:
Z. Zullali, E. Trinh, G. Stebbins, E. Brown, K. Harrison, C. Meng, X. Chen, D. Paredes, K. Comyns, M. Korell, C M. Tanner. Sex Differences in the Reported Prodromal Symptoms of Parkinson’s Disease (PD) in the Fox Insight Cohort [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/sex-differences-in-the-reported-prodromal-symptoms-of-parkinsons-disease-pd-in-the-fox-insight-cohort/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-differences-in-the-reported-prodromal-symptoms-of-parkinsons-disease-pd-in-the-fox-insight-cohort/