Can aspirin prevent dementia? Original paper

In this meta-analysis of cohort studies and randomized controlled trials, there was no association between aspirin use and the risk of incident dementia or Alzheimer’s disease in middle-aged and older adults.

This Study Summary was published on February 12, 2024.

Quick Summary

In this meta-analysis of cohort studies and randomized controlled trials, there was no association between aspirin use and the risk of incident dementia or Alzheimer’s disease in middle-aged and older adults.

What was studied?

Whether aspirin use is associated with a reduced risk of dementia and Alzheimer’s disease.

Who was studied?

A total of 126,740 middle-aged and older adults (average age of 72; approximately 47% men, 53% women).

How was it studied?

This systematic review and meta-analysis included 19 cohort studies and 3 randomized controlled trials (RCTs). The duration of the cohort studies ranged from 3 to 15 years, and the durations of the 3 RCTs were 4.7 years, 7.4 years, and 11.4 years. The overall risk of bias in the included studies was low.

Hazard ratios were calculated to assess the risk of developing dementia and Alzheimer’s disease. A subgroup analysis was focused on low-dose aspirin use (75–100 mg/day).

What were the results?

There was no significant association between aspirin use and the risk of dementia or Alzheimer’s disease. The meta-analysis of RCTs specifically showed a 7.5% reduction in the risk of dementia with aspirin, but this effect was not statistically significant (p=0.09).

Low doses of aspirin (75–100 mg/day) also had no association with the risk of dementia and Alzheimer’s disease.

The included studies displayed high heterogeneity, which complicated the drawing any firm conclusions.

The big picture

In the realm of neurodegenerative research, the quest for effective preventive measures remains a top priority. Alzheimer’s disease, the most common type of dementia, characterized by progressive cognitive decline, poses significant challenges not only for affected individuals but also to healthcare systems worldwide. The exploration of commonly used medications like aspirin for their potentially protective effects against this condition is part of this broader research effort. However, as this study indicates, the journey to find effective preventive strategies is complex and fraught with variables that often yield inconclusive results.

Aspirin, with its anti-inflammatory and antiplatelet properties, emerged as a candidate for preventing dementia due to the hypothesized link between inflammation, vascular health, and neurodegeneration.[1] Early epidemiologic studies supported this hypothesis, showing that nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin were associated with a protective effect on the development of Alzheimer’s disease.[2][3][4] However, later meta-analyses that included not only observational studies but also RCTs indicated there were no benefits of aspirin use for the prevention of Alzheimer’s disease.[1][5][6] Thus, the results of the summarized updated meta-analysis align with these previous findings.

So can it be concluded, based on this consistent evidence, that aspirin use has no benefits for the prevention of Alzheimer’s disease whatsoever? To answer this question, it can be helpful to delve into the summarized study’s limitations, which are not just caveats but crucial factors that could influence the way the results are interpreted. Understanding these limitations is key to contextualizing the findings and managing expectations about the study’s implications.

One notable limitation involves the long latency period associated with Alzheimer’s disease development. One prospective cohort study found that aspirin may need to be taken for at least 10 years to effectively reduce the risk of dementia.[7] This aligns with the significant gap — often over 2 decades — between the onset of pathological changes and the appearance of clinical symptoms. Therefore, shorter durations of aspirin intake, as observed in some study cohorts, might not be sufficient to demonstrate a preventive effect. This distinction is essential for interpreting the results and underscores the importance of long-term medication adherence for potentially mitigating early-stage dementia.

The slow progression of Alzheimer’s disease

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Patient compliance, especially concerning low-dose aspirin use, is another critical factor. Compliance is essential for evaluating medication efficacy, but in the context of neurodegenerative diseases, it becomes particularly challenging. Older adults might struggle with consistent medication intake due to memory trouble or variable pain relief needs. This potential for irregular aspirin use could partly explain the lack of observed effect on dementia onset. However, the summarized study did not investigate the degree of compliance in the included studies, leaving this aspect somewhat unclear.

Additionally, the dose-response relationship of aspirin in the context of dementia prevention remains elusive, largely due to the high variability in aspirin dosages across studies. Some studies looked at dosages of no more than 300 mg per day, while others reported ranges as broad as 75 to 500 mg per day. This inconsistency poses a challenge in determining the optimal aspirin amount for dementia prevention, if any exists.

To answer the question, the lack of a significant link between aspirin use and reduced dementia risk in this study does not close the door on this line of research. Instead, it offers critical insights and prompts further questions. Could different dosages or longer durations of aspirin use yield different results? How might aspirin interact with other risk factors for dementia? Exploring these questions could guide future targeted research.

From a public health perspective, these studies serve as a reminder of the complexity of neurodegenerative diseases and the need for multifaceted prevention and treatment strategies. They also highlight the importance of not prematurely adopting medical practices without robust evidence, particularly in preventing conditions as complex as dementia and Alzheimer’s disease.

Although this study did not find aspirin effective for preventing dementia, it contributes valuable knowledge to the ongoing discourse in neurodegenerative disease research. Each study, regardless of its findings, adds a piece to the puzzle of these complex conditions. This research underscores the need for continued, rigorous exploration in the quest to mitigate the impact of dementia and Alzheimer’s. Progress in medical research is often incremental but always valuable.

This Study Summary was published on February 12, 2024.