Alzheimer’s disease (AD) is a leading cause of dementia, with a rising global burden. Remnant cholesterol (RC), a component of triglyceride-rich lipoproteins, has been implicated in cardiovascular diseases and metabolic disorders, but its role in AD remains unclear. This study investigated the association between RC levels and the risk of AD among elderly patients with type 2 diabetes (T2D) in a real-world clinical setting.
We conducted a retrospective cohort study using electronic medical records from Gongli Hospital of Shanghai Pudong New Area, covering the period from 2013 to 2023. The study included 15,364 elderly patients aged 65-80 years with T2D. RC levels were calculated using the equation. The primary outcome was the diagnosis of AD, validated by neurologists using ICD-10-CM code G30. Cox proportional hazards models were employed to estimate hazard ratios (HRs) for AD across quartiles of RC levels, adjusting for potential confounders.
Over a mean follow-up of 3.69 ± 1.33 years, 312 new cases of AD were identified. A U-shaped relationship was observed between RC levels and AD risk, with the lowest risk associated with RC levels between 0.58-0.64 mmol/L. Both lower (<0.52 mmol/L) and higher (≥0.77 mmol/L) RC levels were linked to increased AD risk. Compared to the reference group (Q2: 0.52-0.64 mmol/L), the adjusted HRs (95% CI) for the lowest and highest quartiles were 1.891 (1.368-2.613) and 1.891 (1.363-2.622), respectively. Each 1 mmol/L increase in RC was associated with a 3.47-fold higher risk of AD (HR=4.474, 95% CI 2.330-8.592).
RC levels may serve as a predictive biomarker for AD risk, with both extremes posing a higher risk. Future studies should explore the mechanistic pathways and potential interventions targeting RC to prevent AD in high-risk populations.