The Portland SEEQ: A Harmonizable Questionnaire for Environmental Exposome Profiling in Prodromal Synucleinopathy

Objective: To describe development of the Portland Suspected Environmental Exposures Questionnaire (SEEQ) and its initial application for environmental exposome profiling in isolated REM sleep behavior disorder (iRBD). Background: Environmental exposures may contribute to Parkinson disease and related synucleinopathies, yet existing instruments variably capture specific agents, co-exposures, exposure uncertainty, timing, and mitigating factors. Methods: SEEQ was iteratively developed to assess pesticides, solvents/industrial chemicals, welding fumes, heavy metals, residential and occupational exposures, and relevant lifestyle factors. Direct exposures were classified as definite, probable, possible, or uncertain/unlikely, with additional assessment of frequency/duration, life stage, and protective-equipment use. SEEQ was administered to participants with polysomnography-confirmed iRBD. Exposure prevalence, co-exposure patterns, and exploratory associations with clinical phenotypes and longitudinal progression were examined. Results: Eighty-three participants completed SEEQ; 81 (97.6%) completed all four direct exposure domains. Definite/probable exposure was reported for pesticides in 38.6%, solvents/industrial chemicals in 43.4%, welding fumes in 21.0%, and heavy metals in 34.1%. Among complete responders, 60.5% reported ≥1 and 42.0% ≥2 direct exposure domains. Forty-five participants identified ≥1 named agent or mixture. Greater exposure burden was cross-sectionally associated most consistently with greater autonomic symptom burden, but was not associated with longitudinal clinical worsening. Conclusion: SEEQ provides a practical, multidomain framework for structured environmental exposome profiling in prodromal synucleinopathy. Larger studies with external exposure validation and longitudinal follow-up are needed.