Elevated Plasma Orexin-A Levels in Prodromal Dementia with Lewy Bodies

Background: Studies on plasma orexin-A levels in prodromal dementia with Lewy bodies (DLB) and the relationship with clinical manifestations are rare. Objective: To assess plasma orexin-A levels and evaluate the correlation with clinical features in patients with mild cognitive impairment with Lewy bodies (MCI-LB) and DLB. Methods: Plasma orexin-A levels were measured in 41 patients with MCI-LB, 53 with DLB, and 48 healthy controls (HCs). Informant-based history, neurological examinations, neuropsychological assessments, laboratory tests, and neuroimaging were collected and the correlation between orexin-A and various indicators evaluated. Results: Plasma orexin-A levels in patients with MCI-LB (1.18 +/- 0.33 ng/mL, p = 0.014) or DLB (1.20 +/- 0.44 ng/mL, p = 0.011) were significantly higher than in HCs (1.02 +/- 0.32 ng/mL) and associated with gender and age. DLB patients with fluctuating cognition (FC) (1.01 +/- 0.23 versus 1.31 +/- 0.50, p = 0.007) or parkinsonism (PARK) (0.98 +/- 0.19 versus 1.25 +/- 0.47, p = 0.030) had significantly lower plasma orexin-A levels than subjects without FC or PARK. Plasma orexin-A levels were significantly negatively correlated with irritability and UPDRS-III scores and significantly positively correlated with disinhibition scores. Conclusion: This is the first report in which elevated plasma orexin-A levels were observed in patients with MCI-LB or DLB. In addition, lower orexin-A levels were found in patients with DLB and FC or PARK compared with HCs. The plasma orexin-A levels were associated with the presence of core features and motor and neuropsychiatric symptoms in patients with MCI-LB and DLB.