Prodromal Association of Non-Motor Symptomatology in Adults With Neurodegenerative Diseases

Early diagnosis of neurodegenerative diseases (NDs) is a priority with the advent of disease-modifying therapies. The study of prodromal non-motor symptoms (NMS) in ND could help guide early diagnosis, facilitating adequate treatment. The primary objective of this study was to determine the prodromal association between NMS and ND.

A retrospective cohort study was planned. Records of subjects attending the movement disorders and NDs unit from Hospital Civil de Guadalajara "Fray Antonio Alcalde," from 2012 to January 2025, were evaluated. Subjects with NMSQuest questionnaire in ND were included. Descriptive and inferential parametric statistics (Student's t-test for independent samples and ANOVA) were used, and odds ratios (OD) with 95% confidence interval were calculated using binary logistic regression. A p value < 0.05 was considered significant.

The most frequent prodromal NMS in ND were depression, constipation, insomnia, anxiety and pain. There was an average of 7.7 ± 7.6 years of prodromal NMS prior to the diagnosis of ND. Prodromal depression [OR 1.9 (1.1-3.5 p < 0.001) and confusion/delusional thoughts [OR 7.2 (1.3-39.2) p = 0.02] were associated with dementia (time onset prior to diagnosis 9.9 ± 12.2 and 5.5 ± 9.7 years, respectively). Prodromal restless legs syndrome was associated with movement disorders [OR 3.3 (1.1-9.7) p = 0.02] (time onset 4.7 ± 6.9 years prior to diagnosis).

Evidence points to a potential association of prodromal NMS in ND. Prospective studies are required to confirm and characterize the association between prodromal NMS and ND, as their early identification may contribute to the timely diagnosis of ND.