LDL cholesterol and statin therapy linked to dementia

Compared with people with elevated levels of low-density lipoprotein cholesterol (LDL-C), researchers report that people with lower levels of LDL-C have a relatively lower risk of developing dementia.

This includes a lower risk of developing Alzheimer’s disease related dementia.

The findings were published on April 1, 2025 the Journal of Neurology Neurosurgery & Psychiatry.

As background the authors noted that the relationship between low- density lipoprotein cholesterol (LDL- C) levels and dementia risk is poorly understood, and there is conflicting evidence on the role of LDL- C and the impact of statin therapy on cognitive outcomes.

“Thus, we aimed to examine the association between low- density LDL- C levels and the risk of dementia and assess the influence of statin therapy,” they said.

The investigators collected and evaluated data from 11 university hospitals, from adult outpatients with no prior diagnosis of dementia who were tracked for at least 180 days after initial LDL-C testing.

The study utilized standard statistical tools to compare subjects with LDL- C levels below 70 mg/dL (1.8 mmol/L) to those with levels above 130 mg/dL (3.4 mmol/L), resulting in an analysis cohort of 108,980 matched patients.

The primary outcome was all-cause dementia, and the secondary outcome was Alzheimer’s disease- related dementia (ADRD).

Data from subjects receiving subsequent diagnoses of dementia indicated 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 declined at lower levels of LDL-C 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.

When LDL-C levels fell below 0.8 mmol/L (<30mg/dL) the reductions in risk disappeared.

Among those subjects with LDL- C <70 mg/dL (<1.8 mmol/L), statin treatment was linked to a 13% reduction in all- cause dementia risk and a 12% decrease in Alzheimer’s disease- related dementia compared with non- users.

The authors concluded, “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.”

“These findings underscore the crucial role of managing LDL-C in lowering dementia risk, they added.