Lower LDL cholesterol associated with lower risk of dementia

A new study shows that maintaining LDL-C levels below 70 mg/dL are associated with a significantly lower risk of all-cause death and Alzheimer's disease-related dementia, even among statin users.

study: Low-density lipoprotein cholesterol levels and risk of developing dementia: Distributed network analysis using a general data model. Image credit: ShutterStock AI Generator / Shutterstock.com

Maintaining low levels of low density lipoprotein cholesterol (LDL-C) levels is important to mediate the risk of future cardiovascular events, but its impact on dementia risk remains unknown. Recent research published in Journal of Neurology, Neurosurgery & Psychiatry We investigate the potential association between LDL-C levels and the risk of dementia.

How does cholesterol affect dementia?

Published observational studies suggest that very low LDL-C levels can cause cognitive decline. However, the findings of recent meta-analyses challenge these findings comprehensively.

Similarly, recent clinical trials involving Fourier and Odyssey have reported that even a significant reduction in LDL-C levels as low as 30 mg/dL (0.8 mmol/L) does not increase the risk of dementia or other cognitive outcomes.

These inconsistent results ensure more targeted studies to reassess the guidelines of LDL-C and their impact on cognitive decline.

About the research

The current study used a large observational cohort to investigate the association between LDL-C levels and the risk of developing dementia, including Alzheimer's disease-associated dementia (ADRD). The researchers also determined whether statin therapy can be used to optimize LDL-C levels to prevent the development of dementia.

All relevant data were obtained from the Observational Health Outcome Partnership (OMOP) Common Data Model (CDM) and the Observational Health Data Science and Informatics (OHDSI) network. Qualified study participants were hospital outpatients over the age of 18 years of age between November 1986 and December 2020.

The index date was set on the day the patient's LDL-C level was measured, and the risk time (TAR) was set one day after the index date. Tar began 180 days from the beginning of the cohort and ended until 99,999 days or the end of the observation period.

Both cohorts were observed for 180 days to minimize biases such as immortal time bias and duplication. Studies that had a history of study participants or ADRDs included in both OMOP-CDM and OHDSI cohorts were excluded from the analysis.

LDL-C levels below 70 mg/dl linked to a reduced incidence of dementia

Of the 12,233,274 patients in both cohorts, 903,711 patients met the eligibility criteria. Of these individuals, 192,213 participants showed LDL-C levels below 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. A total of 108,908 matched pairs for each group were included in the final analysis after propensity scores (PS) matched at a 1:1 ratio.

COX proportional hazards regression analysis compared the risk of ADRD and all-caused dementia among groups with LDL-C levels below 70 mg/dL (1.8 mmol/L) and above 130 mg/dL (3.4 mmol/L) within the overall population.

Reduced LDL-C levels were associated with a reduced risk of ADRD at 26% and 28%, respectively, compared to higher levels of LDL-C levels. LDL-C levels below 55 mg/dL or 1.4 mmol/L were also associated with an 18% reduction in the risk of all-caused dementia and ADRD compared to higher LDL-C levels above 130 mg/dL.

These results were similarly observed in the 1:4 PS matching group, but LDL-C levels below 30 mg/dL were not associated with a reduced risk of dementia compared to LDL-C levels above the 130 mg/dL group.

Among patients prescribed statins, LDL-C levels below 70 mg/dL were significantly lower in risk of all-causal dementia compared to statin users with LDL-C levels above 130 mg/dL, and ADRD was associated with 13% and 14%, respectively. This pattern was similarly observed in the 1:4 PS matching group.

However, LDL-C levels below 55 mg/dL and <30 mg/dL did not result in a statistically significant reduction in the risk of dementia compared to LDL-C levels above 130 mg/dL.

The findings indicate that statin use did not lead to a significant reduction in the risk of dementia in patients with LDL-C levels below 55 mg/dL. In comparison, a significant reduction in all-causal dementia risk and ADRD of 13% and 12% was observed among statin users with LDL-C levels below 70 mg/dL, compared to non-users.

The use of statins in individuals with LDL-C levels above 130 mg/dL was associated with a 7% and 10% reduction in all-causal dementia risk and ADRD, respectively, compared to non-users. This reduced risk was observed in both lipophilic and hydrophilic statin users.

Conclusion

Individuals with LDL-C levels below 70 mg/dL or 55 mg/dL at baseline had a significantly reduced risk of developing all-caused dementia and ADRD compared to patients with high LDL-C levels. This association persisted even among statin users.

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