Long-term NSAID use may reduce the risk of dementia

Research has shown that persistent use of NSAIDs may protect the brain from dementia, particularly for individuals who are not genetically predisposed. Anti-inflammatory Is medicine key to healthy aging?

study: Long-term exposure to nonsteroidal anti-inflammatory drugs associated with dementia risk. slladkaya / shutterstock.com

Recent research published in Journal of the American Geriatrics Society Determine whether long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of developing dementia.

What causes dementia?

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

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

NSAIDs and the risk of dementia

NSAID is an anti-inflammatory analgesic that inhibits the enzyme activity of cyclooxygenase 1 (COX-1) and COX-2. Previous In vain Studies have demonstrated that NSAID exposure may reduce amyloid-β plaque formation in the brain of mice.

Similarly, one meta-analysis revealed that NSAID users are less likely to develop dementia compared to non-users. However, these findings were inconsistent with another meta-analysis showing that there was no effect of NSAID use on dementia risk.

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

About the research

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

The Rotterdam Study began enrolling participants over the age of 55 in 1990. 14,926 individuals were ultimately included in the final study cohort, compared to the initiation of the study in which 7,983 individuals were enrolled. All participants will be followed up at a dedicated research center every four years.

A total of 13,507 study participants provided follow-up informed consent through their medical records without dementia at the time of enrollment. A subcohort consisting of dementia-free individuals who were then matched by age and gender were created for each date when a diagnosis of dementia was reported.

Survey results

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

Long-term use of NSAIDs was reported more frequently in women than in men. Compared to short-term users, long-term NSAID users have a higher body mass index (BMI) value and are more likely to be diagnosed with diabetes.

Approximately 30%, 5.8%, and 45.6% of the cohort used NSAIDs with Aβ42-reducing properties, non-Aβ42-reducing NSAIDs, and both. Approximately 17.8% of study participants had an average follow-up period of 14. They were diagnosed with dementia after 5 years. In particular, 73.4% of study participants diagnosed with dementia were diagnosed with clinical AD.

Compared with non-NSAID users, short- and medium-term use of NSAIDs was associated with an increased risk of all-causal dementia. However, long-term NSAID users who have used these drugs for more than two years are less likely to be diagnosed with dementia. Cumulative NSAID doses were not associated with dementia risk.

Sensitivity analysis revealed that use of NSAIDs for less than 24 months reduces the risk of developing dementia, whereas use of NSAIDs between 12 and 24 months is associated with a slight increase in the risk of dementia. Compared to Aβ42-reduced NSAIDs, non-Aβ42-reduced NSAIDs were effective in reducing all-causal dementia and clinical AD risk.

The effect of long-term NSAID use in reducing the risk of all-causal dementia was observed only in participants lacking the apoe-poprotein ε4 (apoe-ε4) allele, but none of those with the apoe-ε4 allele were observed. Long-term use of acetylsalicylic acid did not affect the risk of dementia.

Conclusion

Long-term use of NSAIDs reduced the risk of developing dementia rather than short-term use. Importantly, this beneficial effect was dependent on the duration of use, not on the cumulative dose.

The findings show that long-term use of anti-inflammatory drugs can prevent the development of dementia. Nevertheless, additional studies are needed to assess the potential of anti-inflammatory drugs in the prevention of dementia.

Long-term inhibition of harmful inflammatory processes is more effective in preventing dementia than exposure to high cumulative doses. ”