The effect of statins use on the incidence of Alzheimer's disease (AD) is still under debate, and it could be modified by a series of factors.

We aimed to examine the association of statins use with the risk of cognitive impairment and AD, and assess the moderating roles of genetic susceptibility and other individual-related factors.

A longitudinal study was conducted from the UK Biobank where individuals completed baseline surveys (2006–2010) and were followed (mean follow-up period: 9 years).

A population-based study.

A total of 371,019 dementia-free participants (mean age 56.4 years; 53.6% female).

The effects of statins use on cognitive performance and incident AD were examined by using linear regression model and Cox proportional hazards regression model, respectively. We further evaluated the moderating roles of genetic risks and individual-related factors on both multiplicative and additive scales.

The findings showed statins use was associated with an increased risk of AD development [hazard ratio (HR) 1.19 (95% CI: 1.08, 1.30)] compared with no use of statins. We further found significant negative additive interactions of statins use with APOE ε4 allele. Besides, the effects of statins use would be modified by age, sex and cardiovascular diseases (CVDs).

A protective effect of statins use was observed in those who carried two APOE ε4 alleles. Also, sex, age and CVDs could modify the effects of statins use, which would provide insights for the guideline of the statins therapy.