Low LDL cholesterol levels linked to reduced risk of dementia: Study

People with low levels of low-density lipoprotein cholesterol (LDL-C) in their blood have a lower risk of dementia, including lower risk of Alzheimer’s disease related dementia, shows a study published online today in the Journal of Neurology Neurosurgery & Psychiatry.

Use of statins conveyed an additional protective effect for people with low LDL-C, specifically those with blood levels less than 1.8 mmol/L (<70 mg/dL), reducing their risk of dementia even further.

However, reducing LDL-C to very low levels below 0.8 mmol/L (<30mg/dL) did not reduce dementia risk further.

The benefits of low LDL-C levels to protect against cardiovascular events is well recognised, but the relationship between LDL-C levels and dementia has been less clear, particularly the cut-off for LDL-C below which there is no further benefit for reducing risk of cognitive decline.

To address this, the authors accessed data collected by 11 university hospitals on adult outpatients with no previous diagnosis of dementia followed for at least 180 days after LDL-C testing. They identified 192,213 people with LDL-C levels less than 1.8 mmol/L (<70mg/dL) and 379,006 patients with LDL-C levels more than 3.4 mmol/L (>130mg/dL), and matched individuals in each group into 108,980 matched pairs.

Analysis of subsequent diagnoses of dementia showed that LDL-C levels below 1.8 mmol/L (<70mg/dL) were associated with a 26% reduction in the risk of all-cause dementia and a 28% reduction in the risk of Alzheimer’s disease related dementia, compared with LDL-C levels above 3.4 mmol/L (>130mg/dL).

The protective effect against cognitive decline lessened at lower LDL-C levels and eventually disappeared entirely. At LDL-C levels below 1.4 mmol/L (<55mg/dL), there was an 18% risk reduction for both all cause dementia and Alzheimer’s disease related dementia compared with LDL-C levels above 3.4 mmol/L (>130mg/dL), and when LDL-C levels fell below 0.8 mmol/L (<30mg/dL) the risk reductions disappeared.

Statin use conferred additional protection against dementia in the presence of low LDL-C levels. Among people with LDL-C levels below 1.8 mmol/L (<70mg/dL), statin use was associated with a 13% reduction in all cause dementia risk and a 12% decrease in risk of Alzheimer’s disease related dementia compared with non-users.

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. The authors also acknowledge that the study has some limitations including the potential for unmeasured confounding factors because of its retrospective design, possible underreporting of dementia cases due to variations in diagnostic accuracy between hospitals, and the focus on baseline LDL-C levels when lipid profiles could change over time.

Nevertheless, the authors conclude: “Low LDL-C levels (<70 mg/dL (<1.8 mmol/L)) are significantly associated with a reduced risk of dementia, including Alzheimer’s disease related dementia, with statin therapy providing additional protective effects.”

They add: “These findings underscore the crucial role of managing LDL-C in lowering dementia risk.”

Reference:

Lee M, Lee KJ, Kim J, et alLow-density lipoprotein cholesterol levels and risk of incident dementia: a distributed network analysis using common data modelsJournal of Neurology, Neurosurgery & Psychiatry Published Online First: 01 April 2025. doi: 10.1136/jnnp-2024-334708