The association between statin use and Alzheimer's disease (AD) risk, especially in relation to the APOE ε4 allele, has been unclear. A recent longitudinal cohort study aimed to investigate whether statin initiation affects incident AD and cognitive decline differently depending on APOE ε4 status. This study was published in the Neurology journal by Kumar Rajan and colleagues.
Alzheimer's disease is a progressive neurodegenerative disorder, and identifying interventions to reduce its risk is crucial.Statins, commonly used to manage cholesterol levels, have been proposed as potential candidates due to their anti-inflammatory and neuroprotective properties. However, the impact of statin use on AD risk remains debated.

The study, conducted in urban communities in Chicago, involved 4,807 participants with a mean age of 72 years, including 63% female and 61% non-Hispanic Black individuals. Statin initiation and incident AD diagnoses were recorded during the study period, along with cognitive assessments. The association between statin use and AD risk was analyzed, considering APOE ε4 allele status.
The key findings of the study were:
• 31% of participants reported statin initiation during the study period.
• Statin initiation was associated with a reduced risk of incident clinical AD, especially among those with the APOE ε4 allele.
• Among APOE ε4 carriers, statin initiation was linked to a significantly lower risk of incident AD compared to non-users.
• APOE ε4 carriers also experienced slower declines in global cognition and episodic memory after statin initiation.
• However, the association between statin use and cognitive decline was not significant in individuals without the APOE ε4 allele.
The study suggests that statin use may be associated with a reduced risk of incident AD, particularly in individuals carrying the APOE ε4 allele. These findings highlight the potential benefits of statin therapy in reducing AD risk, especially among those genetically predisposed to the disease. Further research, including randomized clinical trials, is warranted to confirm these results and explore the mechanisms underlying this association.
Statin initiation may be linked to a lower risk of Alzheimer's disease, especially among individuals with the APOE ε4 allele. These findings provide valuable insights into potential preventive strategies for AD and emphasize the importance of personalized approaches to treatment.
Reference:
Rajan, K. B., Mcaninch, E. A., Wilson, R. S., Dhana, A., Evans-Lacko, S., & Evans, D. A. Statin initiation and risk of incident Alzheimer disease and cognitive decline in genetically susceptible older adults. Neurology,2024;102(7). https://doi.org/10.1212/wnl.0000000000209168