Lipid-Related Metabolic Dysregulation Affects Survival in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND

Idiopathic normal pressure hydrocephalus (iNPH) is associated with increased mortality and vascular-metabolic comorbidity, but prognostic biomarkers are lacking.

OBJECTIVES

To assess the triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio, an insulin resistance (IR) marker, and its associations with MRI glymphatic markers and mortality in iNPH.

METHODS

We conducted a dual-center longitudinal study including 67 iNPH patients and 37 matched controls. Baseline lipid profiles were assessed, enlarged perivascular spaces (EPVS) were rated on 3 T MRI in a subgroup, differences were tested by ANCOVA, and mortality associations by adjusted Cox models.

RESULTS

iNPH patients showed higher triglycerides and TG/HDL-C and lower HDL-C. High-grade centrum semiovale (CSO)-EPVS were associated with higher TG/HDL-C. TG/HDL-C showed the strongest mortality association. A model combining TG/HDL-C with CSO-EPVS showed the best fit, suggesting synergy.

CONCLUSIONS

iNPH exhibits a lipid profile associated with IR linked to glymphatic alterations and mortality. Moreover, despite requiring large-scale validation, combined-marker models are promising.