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

Studies on plasma orexin-A levels in prodromal dementia with Lewy bodies (DLB) and the relationship with clinical manifestations are rare.

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.

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.

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.

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.