Long-term NSAID use may reduce the risk of dementia

Long-term NSAID use may reduce the risk of dementia

Research shows that sustained NSAID use can protect the brain from dementia, especially for those without a genetic predisposition - could your anti-inflammatory drug be crucial for healthy aging?

Study:Long-term exposure to nonsteroidal anti-inflammatory drugs in relation to dementia risk. Slladkaya / Shutterstock.com

A recently published study in theJournal of the American Geriatrics Society Determines whether long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of developing dementia.

What causes dementia?

Long-term NSAID use significantly reduced the risk of dementia in people without the APOE ε4 genetic variant, suggesting that genetics may influence the effectiveness of treatment.

Dementia is characterized by a gradual decline in brain function. Inflammation is a common feature of various pathophysiological changes that contribute to the development of dementia, some of which include vascular brain injury and the accumulation of amyloid-β and tau proteins.

Hypertension, atherosclerosis, hypoperfusion, amyloid-β, and tau protein accumulation activate chronic neuroinflammatory responses that subsequently increase the risk of dementia. Chronic neuroinflammation leads to greater vascular damage and amyloid-β and tau accumulation by inducing endothelial dysfunction and reducing the integrity of the blood-brain barrier (BBB).

NSAIDS and risk of dementia

NSAIDs are anti-inflammatory analgesic agents that inhibit the enzymatic activity of cyclooxygenase 1 (COX-1) and COX-2. PreviousIn vivoStudies have shown that NSAID exposure can reduce amyloid-β plaque formation in the brains of mice.

Likewise, a meta-analysis found that NSAID users were less likely to develop dementia compared to non-users. However, these results were refuted by another meta-analysis, indicating no influence of NSAID use on dementia risk.

To date, few observational studies have evaluated the association between long-term NSAID use and dementia risk.

About the study

Interestingly, NSAIDs that lack amyloid-lowering properties were more strongly associated with a reduced risk of dementia than those known to lower amyloid beta.

The current study obtained data from the Rotterdam Study, an ongoing population-based cohort study conducted in the Netherlands. These data were used to determine the effects of long-term and cumulative doses of NSAIDs on dementia risks and how these drugs may reduce amyloid burden in the brain.

The Rotterdam Study began enrolling participants 55 and older in 1990. Compared to the start of the study, which enrolled 7,983 people, 14,926 people were ultimately included in the final study cohort. All participants undergo follow-up testing every four years at a dedicated research center.

A total of 13,507 study participants were dementia-free at enrollment and provided informed consent for follow-up through medical records. At each time point at which a dementia diagnosis was reported, a sub-cohort of dementia-free individuals matched for age and gender at that time point was created.

Study results

At the start of the study, the average age of the study participants was 66.2 years and 59.5% were female. During the follow-up period, approximately 81% of the cohort used NSAIDs, reflecting 93,859 cumulative months of NSAID use.

Long-term use of NSAIDs has been reported more frequently in women than in men. Compared to short-term users, long-term NSAID users were more likely to have greater body mass index (BMI) values ​​and be diagnosed with diabetes.

Prolonged use of aspirin (acetylsalicylic acid) did not show a protective effect against dementia despite its similarity to NSAIDs, highlighting the unique properties of various anti-inflammatory drugs.

Approximately 30%, 5.8%, and 45.6% of the cohort used NSAIDs with Aβ42-low properties, non-β42-low NSAIDs, or both, respectively. Approximately 17.8% of study participants were diagnosed with dementia after a median follow-up of 14.5 years. Notably, 73.4% of study participants diagnosed with dementia were diagnosed with clinical AD.

Compared to non-NSAID users, short- and moderate-term NSAID use was associated with an increased risk of overall dementia. However, long-term NSAID users who have been using these medications for over two years were less likely to be diagnosed with dementia. Cumulative NSAID doses were not associated with dementia risks.

Sensitivity analysis found that less than 24 months of NSAID use reduced the risk of dementia, while 12-24 months of NSAID use was associated with a marginal increase in dementia risk. Compared with Aβ42-low NSAIDs, non-Aβ42-low NSAIDs were more effective in reducing overall dementia and clinical AD risk.

The effects of long-term NSAID use in reducing the risk of dementia from overall losses were observed only in participants lacking the apolipoprotein ε4 (apoe-ε4) allele, but not those with the APOE ε4 allele. Prolonged use of acetylsalicylic acid had no influence on the risk of dementia.

Conclusions

Long-term use of NSAIDs, but not short-term, reduced the risk of dementia. Importantly, this beneficial effect depends on the duration of use and not the cumulative dose.

The study results show that prolonged use of anti-inflammatory drugs could prevent the onset of dementia. Nevertheless, additional research is needed to evaluate the potential of anti-inflammatory drugs in preventing dementia.

Long-term inhibition of harmful inflammatory processes, rather than exposure to a high cumulative dose, is more effective in preventing dementia. “

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