Lower LDL cholesterol linked to reduced dementia risk

New research shows that maintaining LDL-C levels under 70 mg/dl is associated with a considerably lower risk of all cause and Alzheimer-related dementia-even among statin users.

Study: Lipoprotein cholesterol levels with low density and the risk of incident dementia: a distributed network analysis using common data models. Image Credit: Shutterstock AI Generator / Shutterstock.com

Although maintaining low levels of lipoprotein cholesterol (LDL-C) with low density, it is crucial to mediate the risk of future cardiovascular events, the impact on the risk of dementia remains unclear. A recent study published in Journal of Neurology, Neurosurgery and Psychiatry Investigates the potential association between LDL-C levels and the risk of dementia.

How does cholesterol affect dementia risks?

Published observational studies suggest that very low LDL-C levels can cause cognitive decline. However, recent findings of meta-analysis have fully challenged these findings.

Likewise, recent clinical studies, including Fourier and Odyssey, have reported that even a significant reduction in the LDL-C levels, even as low as 30 mg/dl (0.8 mmol/l), does not increase the risk of dementia or other cognitive results.

These conflicting results justify more focused research to evaluate LDL-C guidelines and their impact on cognitive decline.

About the study

The current study investigated the association between LDL-C levels and the risk of developing dementia, including all causes and Alzheimer’s disease-related dementia (ADRD) with the help of a large observational cohort. The researchers also determined whether the optimization of LDL-C levels with the help of statin therapy could prevent the development of dementia.

All relevant data was obtained from the networks of the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) and Observational Health Data Sciences and Informatics (OHDSI) networks. Eligible participants in the study were 18 years or older and outpatient clinics of the hospital between November 1986 and December 2020.

The index date was determined on the day on which the patient’s LDL-C levels were measured, with the time-on-risk (TAR) set on one day after the index date. Tar started 180 days from the start of the cohort and ended 99,999 days or until the observation period ended.

To minimize prejudices, such as the preference for immortal time and duplication, both cohorts were observed for a period of 180 days. Each study participant included in both Otop-CDM and OHDSI cohorts or had a history of ADRD was excluded from the analysis.

LDL-C levels under 70 mg/dl linked to lower dementia incidence

Of the 12,233,274 patients from both cohorts, 903,711 patients met the eligible criteria. Among these persons, 192,213 participants showed LDL-C levels under 70 mg/dl or 1.8 mmol/l, while 379.006 patients reported LDL-C levels above 130 mg/dl or 3.4 mmol/l. After Propensity Score (PS) corresponded to a 1: 1 ratio, a total of 108,908 matched pairs of each group were included in the final analysis.

COX proportional danger regression analyzes were performed to compare ADRD and dementia risk on all causes between groups with LDL-C levels under 70 mg/dl (1.8 mmol/l) and more than 130 mg/dl (3.4 mmol/l) within the total population.

Lower LDL-C levels were associated with a reduced risk of dementia due to all causes and ADRD in 26% and 28% respectively, compared to higher LDL-C levels. LDL-C levels under 55 mg/dl or 1.4 mmol/l were also associated with an 18% reduced risk of dementia due to all causes and ADRD compared to higher LDL-C levels of 130 mg/dl or higher.

Although these results were observed in the same way with 1: 4 PS matching groups, LDL-C levels under 30 mg/dl were not associated with a reduced risk of dementia compared to LDL-C levels above 130 mg/DL group.

Among patients prescribing statins, LDL-C levels under 70 mg/dl were associated with a significantly lower risk of dementia due to all causes and ADRD with 13% and 14% respectively, compared to statin users with LDL-C levels of more than 130 mg/dl. This pattern was observed in the same way in groups of 1: 4 ps-tailored groups.

However, LDL-C levels under 55 mg/dl and 30 mg/dl did not lead to a statistically significant reduction in the risk of dementia compared to LDL-C levels of 130 mg/dl or higher.

The research results indicate that the use of the statin did not lead to a significant reduction in dementia risk in patients with LDL-C levels less than 55 mg/dl. For comparison: for Statin users with LDL-C levels less than 70 mg/dl, a significant reduction in dementia risks and ADRD by 13% and 12% respectively was observed in comparison with non-users.

Statin use in persons with LDL-C levels higher than 130 mg/dl was associated with a reduced risk of dementia due to all causes and ADRD by 7% and 10% respectively, compared to non-users. This reduced risk was observed with both lipophilic and hydrophilic statin users.

Conclusions

Persons with LDL-C levels under 70 mg/dl or 55 mg/dl at the start were a considerably reduced risk of developing dementia due to all causes and ADRD compared to those with high LDL-C levels. This association continued even with Statin users.

These findings support the need for targeted lipid management as a preventive strategy against dementia. “