Objective: To investigate biological changes in early prodromal Lewy body disease (LBD) using routine health checkup data.

Background: Various prodromal symptoms appear years before LBD onset, and several cohort studies have reported prodromal and risk markers. However, longitudinal studies examining laboratory findings alongside prodromal symptoms before they fully develop remain limited. In Japan, annual health checkups are mandated for workers under the Industrial Safety and Health Act. Since 2017, we have conducted a cohort study among health checkup examinees using self-administered questionnaires. Individuals aged ≥50 years with abnormalities in two or more of SCOPA-AUT (autonomic dysfunction), SAOQ (hyposmia), and RBDSQ (REM sleep behavior disorder) were defined as prodromal LBD high-risk (HR), whereas those with all normal were defined as low-risk (LR). We reported that about 6% were classified as HR, and one-third of them showed abnormalities on DaT-SPECT or MIBG myocardial scintigraphy.

Method: From 2017 to 2025, questionnaires assessing non-motor symptoms (SCOPA-AUT, SAOQ, RBDSQ, BDI-II for depression, and ESS for daytime sleepiness) and health checkup data were collected at three centers. We compared 73 individuals who converted to HR after ≥4 years (HR conversion group) with 630 who remained LR for ≥4 years using linear mixed-effects models.

Results: At baseline, the HR conversion group had higher SCOPA-AUT, RBDSQ, BDI-II, and ESS scores and lower SAOQ scores than the LR group. The inter-group differences of BDI-II were greater than those of other scores. Longitudinally, SCOPA-AUT, SAOQ, and RBDSQ worsened faster towards conversion to high-risk state. No differences were found for the trajectories of BDI-II or ESS. Adjustment for BDI-II did not substantially alter the trajectories of SCOPA-AUT, SAOQ, or RBDSQ. Among the checkup items, eGFR and CRP were higher, and creatinine was lower at baseline. Differences of trajectories were observed in waist circumference, hemoglobin, hematocrit, triglycerides, HDL cholesterol, albumin, and amylase. SCOPA-AUT changes were associated with HDL and albumin, and SAOQ with triglycerides.

Conclusion: Our results suggest that depressive symptoms are relatively severe at the early prodromal stage of LBD but progress more slowly over time than other non-motor symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-longitudinal-changes-in-non-motor-symptoms-and-routine-health-checkup-parameters-around-the-emergence-of-prodromal-features-of-lewy-body-disease/