Associations of plasma lipid burden with cognitive performance and decline across dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease dementia

BackgroundPeripheral lipid dysregulation has been implicated in neurodegeneration, but most studies have focused on single lipid measures within one dementia subtype.ObjectiveTo determine whether a composite plasma lipid burden score (PLBS), derived from routine fasting lipid indices, differs across dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and Parkinson's disease dementia (PDD) and whether it relates to baseline cognition and subsequent cognitive decline.MethodsWe conducted a longitudinal observational study including 227 patients with probable DLB (n = 65), AD (n = 79), or PDD (n = 83). PLBS was defined as the unweighted mean of z-standardized non-HDL cholesterol, remnant cholesterol, apolipoprotein B, apolipoprotein B/apolipoprotein A1, LDL-C/HDL-C, triglyceride/HDL-C, and triglyceride-glucose index. Multivariable linear regression and linear mixed-effects models were used to examine associations with baseline cognition and annualized cognitive decline.ResultsPLBS differed significantly across diagnoses and showed the clearest separation among lipid-related measures, with higher values in DLB and PDD than in AD. Higher PLBS was associated with poorer baseline global cognition and faster longitudinal decline. These associations appeared to be numerically more pronounced in DLB, with intermediate estimates in PDD and weaker estimates in AD in this exploratory analysis. Higher PLBS was linked to poorer attention and visuospatial/executive performance and greater rapid cognitive decline.ConclusionsAn adverse plasma lipid burden profile is associated with worse cognition and faster decline across degenerative dementias, with the strongest effects in DLB. Routinely lipid-derived indices may complement existing approaches to longitudinal risk assessment. These findings require independent external validation and formal evaluation of predictive performance before clinical application.