Despite its potential clinical significance, non-motor symptoms (NMS) in the prodromal phase of neurodegenerative diseases (ND) are still poorly understood. The study by Villa-Villegas et al.^{Reference Villa-Villegas, Farías-Moreno, González-Ruffino and Zúñiga-Ramírez1} contributes to our understanding of this topic, offering a compelling investigation of early non-motor features across a large and diverse cohort. The authors used a slightly modified version of the NMSQuest,^{Reference Chaudhuri, Martinez-Martin and Schapira2} originally developed for Parkinson’s disease (PD), to screen for NMS across ND categorized in the realms of dementias, movement disorders and motor neuron disease. The study’s large sample size (n = 674) and systematic attempt to classify NMS according to disease category, temporality and gender are among its notable strengths. Particularly interesting and clinically relevant is the observation of identifiable prodromal NMS linked to certain NDs, such as depression and delusions with dementia and restless legs syndrome with movement disorders. The possibility of earlier clinical suspicion and referral for appropriate care is further highlighted by the finding that some NMS, such as constipation or rapid eye movement (REM) sleep behavior disorder, may be diagnosed more than ten years before others.^{Reference Postuma, Gagnon and Vendette3,Reference Zhou, Wang and Zhou4}

Nevertheless, there are important drawbacks to the retrospective design. Most significantly, the reliability of the time-onset estimates is compromised by recall bias and missing data, particularly in individuals with cognitive decline. Despite being a well-validated tool in PD, the NMSQuest^{Reference Chaudhuri, Martinez-Martin and Schapira2} introduces interpretive caution when applied to other NDs without formal validation. Despite acknowledging this limitation, the authors argue that the questionnaire is more broadly applicable because of symptom overlap and frequent co-pathology seen in the disorders studied, a claim that needs more empirical backing. The varied diagnostic standards used are another area of criticism. Diagnostic certainty across ND categories, for example, is not fully discussed, and “parkinsonism” is not clearly distinguished from PD. Furthermore, although this is openly acknowledged, meaningful subgroup analysis is limited by the comparatively small sample sizes for less common disorders such as amyotrophic lateral sclerosis, progressive supranuclear palsy or dystonia.

In addition to their provocative and potentially game-changing proposal to expand the use of NMSQuest – pending prospective validation – the authors’ call for systematic screening of prodromal NMS in at-risk populations is well-founded. In order to improve diagnostic accuracy, future studies should validate prodromal NMS across ND subtypes in longitudinal designs, ideally backed by imaging data or biomarkers.^{Reference Fereshtehnejad, Zeighami, Dagher and Postuma5}

Overall, this study generates hypotheses and is timely. In addition to laying the groundwork for future prospective work to improve diagnostic and therapeutic windows in neurodegeneration, it initiates a crucial conversation regarding early symptom detection in ND.