HDL cholesterol indicates neurodegenerative vulnerability in dementia with lewy bodies

Altered lipid metabolism has been implicated in neurodegenerative disorders; however, its relevance to dementia with Lewy bodies (DLB) remains incompletely characterized. This study examined associations between plasma lipid profiles, lipid-related inflammatory indices, and clinical and neurodegenerative features in drug-naive patients with DLB, with comparisons to age-matched healthy controls. Plasma levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol did not differ significantly between patients with DLB and controls, whereas triglyceride (TG) levels were significantly lower in DLB (p = 0.002). Within the DLB cohort, higher HDL-C levels were associated with less severe neurodegenerative changes, including milder nigrostriatal degeneration (β = 0.448, p = 0.005), lower motor symptom severity (β = -0.324, p = 0.047), and a reduced prevalence of visual hallucinations (OR = 0.924, p = 0.006). In contrast, higher TG levels and an increased TG-to-HDL-C ratio were associated with more pronounced neurodegenerative involvement (TG: β = -0.358, p = 0.021; TG-to-HDL-C ratio: β = -0.426, p = 0.006). Greater neurodegenerative severity was also associated with lipid-related inflammatory markers, including the neutrophil-to-HDL-C ratio (β = -0.491, p = 0.001) and the platelet-to-HDL-C ratio (β = -0.301, p = 0.040), suggesting that inflammation may act as a contributory or mediating process. Collectively, these findings indicate that plasma lipid profiles-particularly HDL-C-are associated with neurodegeneration and clinical manifestations in DLB, extending beyond isolated dopaminergic involvement. An HDL-C-related neurodegenerative framework, with inflammation as a modifying process, may better reflect the underlying pathophysiology of DLB and warrants further longitudinal investigation.