Serum ferritin levels linked to cognitive decline and biomarker profiles in dementia with lewy bodies.

Objective: Elevated serum ferritin levels have been associated with neurodegenerative diseases, yet their specific role in dementia with Lewy bodies (DLB) remains insufficiently explored.

Method: A total of 434 participants were enrolled, including 217 controls, 217 Alzheimer's disease (AD) patients, and 89 DLB patients. Demographic and clinical characteristics, cognitive performance, and neurobehavioral symptoms were evaluated. Serum ferritin levels were stratified into quartiles, and logistic regression models were used to examine the association between ferritin levels and the risk of DLB. Additionally, biomarker profiles of Aβ42, Aβ40, t-tau, and p-tau were analyzed across ferritin quartiles in DLB patients.

Results: DLB patients exhibited the most severe neurobehavioral symptoms (NPI: 11.09 ± 1.24) and significant cognitive impairment (MMSE: 14.16 ± 6.81; MoCA: 9.77 ± 6.20) compared to controls. Higher serum ferritin levels were significantly associated with increased DLB risk, with the highest quartile showing an adjusted odds ratio of 7.58 (95% CI: 2.52-22.81). In DLB patients, ferritin levels were significantly associated with Aβ42 (p < 0.001), with Aβ42 concentrations following a U-shaped distribution across quartiles, suggesting a complex interplay between ferritin and amyloid pathology. Aβ40, t-tau, and p-tau showed weaker or non-significant associations.

Conclusion: Elevated serum ferritin levels are strongly associated with an increased risk of DLB and may modulate amyloid pathology, particularly Aβ42. These findings underscore the relevance of iron metabolism in the pathophysiology of DLB and suggest ferritin as a potential biomarker for diagnosis and disease monitoring.