Low dose acetylsalicylic acid (LDASA) may have some protective benefit against cognitive decline, but only if started well before symptoms begin, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.
The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant.
The study, which was reported in MDedge after the 2021 Alzheimers Association International Conference (AAIC) in Denver, differed from previous observational and randomised, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to two decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made.
“The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany, who presented the study's results at the 2021 AAIC.
Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of more than 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Nguyen.
Not yet a definitive answer
Although the findings are promising, she noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up." She plans to conduct similar studies in non-white populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.
The study is interesting, said Dr Claire Sexton, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
Meta-analysis data
The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 or older.
The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).
There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13). The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).
The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).
Study details
Low-dose acetylsalicylic use shows protective association with Alzheimer’s disease incidence: results from two large prospective cohort studies
Presenting author Thi Ngoc Mai Nguyen, Network Aging Research, Heidelberg University; author, Ben Schöttker, German Cancer Research Center.
Presentation at Alzheimer's Association International Conference on 28 July 2021
Abstract
Background
Acetylsalicylic acid (ASA), through multiple mechanisms, has been assigned a potential protective effect on dementia development. However, observational studies and randomised trials have yielded conflicting results so far.
Method
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.
Result
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, 5,177 were diagnosed with dementia, including 1,885 AD cases and 1,281 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.
Conclusion
Individuals who used low-dose ASA had a reduced 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 ε4/ε4 positive status or family history of early onset AD) should consider starting low-dose ASA use already in middle adulthood (at age 40-50 years) as a preventive measure against AD development at an older age.
MDedge article – Low-dose aspirin linked to lower dementia risk in some (Open access)
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