(P-550) Low-dose Acetylsalicylic Use Shows Protective Association with Alzheimer’s Disease Incidence: Results from Two Large Prospective Cohort Studies

Background: Acetylsalicylic acid (ASA), through multiple mechanisms, has been assigned a potential protective effect on dementia development. However, observational studies and randomized trials have yielded conflicting results so far.

Objectives: To identify the longitudinal association of low-dose acetylsalicylic use and the incidence of dementia.

Methods: Cox regression models, adjusted for a propensity score to model the underlying cardiovascular risk, were used to assess the longitudinal associations of low-dose ASA use with all-cause dementia, Alzheimer’s disease (AD) and vascular dementia (VD) incidence in two population-based cohorts: the ESTHER cohort from Germany with 6,049 participants, and the UK Biobank cohort with a total of 501,392 participants.

Results: Over a median of 14.3 years of follow-up, 481 all-cause dementia cases, including 158 AD and 183 VD cases were diagnosed in ESTHER. In the UK Biobank, 5177 were diagnosed with dementia, including 1885 AD cases and 1281 VD cases during a follow-up time of 8.9 years. In the ESTHER study, participants who used low-dose ASA had a reduced risk of 21% for all-cause dementia (hazard ratio-HR [95% confidence interval-CI]: 0.79 [0.62-1.02]), of 46% for AD (HR [95%CI]: 0.57 [0.35-0.92]) but there was no association with VD. Results pointed towards the same direction in UK Biobank cohort, with a reduced risk of 11% (HR [95%CI]: 0.89 [0.82-0.96]) for all-cause dementia and 14% (HR [95%CI]: 0.86 [0.76-0.99]) for AD, while there was a null result for VD.

Conclusions: Individuals who used low-dose ASA had a reduced the risk of total dementia and AD incidence in two independent cohort studies. In patients with pre-existing cardiovascular conditions, who have an indication for low-dose ASA use anyway, it should be taken care that they get low-dose ASA prescribed and are compliant. Moreover, other individuals with known high AD risk (e.g., because of APOE 4/4 positive status or family history of early onset AD) should consider to start low-dose ASA use already in middle adulthood (at age 40-50 years) as a preventive measure against AD development at older age.