Opioid use above 90 total standardized doses closely associated with increased dementia risk: JAMA

A new study published in the Journal of American Medical Association showed that fewer than 90 total standardized doses (TSDs) of opioids were not substantially linked to an increased risk of dementia. With over 10 million new cases reported each year and a fast rising incidence worldwide, dementia is becoming a more serious public health concern. Between 2000 and 2019, the usage of opioids quadrupled more than usual throughout the globe. Although opioids have been investigated as a possible risk factor for dementia, there is little data linking long-term noncancer opioid usage and the sole use of mild opioids to an increased risk of dementia. Thus, Nelsan Pourhadi and colleagues carried out this investigation to evaluate the relationship between the risk of age-related all-cause dementia and the cumulative noncancer usage of opioids.

In this population-based cohort nested case-control research, 1,872 854 people without a history of dementia, opioid addiction, cancer, or opioid use in terminal illness were included. Every person with dementia during follow-up was incidence-density matched to 5 controls who did not have dementia. The period of statistical analysis was August 2023 to March 2024. The total amount of opioid exposure was calculated using filled prescriptions from 1995 to 2020. The main findings of this study were adjusted incidence rate ratios (IRRs) for the relationships between opioids and dementia, which were obtained using conditional logistic regression.

A total of 93,638 of the 1,872 854 participants in the trial who had no prior history of dementia, opioid addiction, cancer, or opioid use in terminal illness acquired all-cause dementia during follow-up. These participants were matched to 468 190 control participants. The risk of dementia was not consistently linked to the use of opioids up to 90 total standardized doses. Increased IRRs of dementia occurring before the age of 90 years were found for opioid exposure above 90 TSDs. These IRRs ranged from 1.29 for 91 to 200 TSDs to 1.59 for higher than 500 TSDs for age-band 60 to 69 years at dementia diagnoses.

For the age group of 70 to 79 years, the corresponding IRRs were 1.16 to 1.49, and for the age group of 80 to 89 years, they were 1.08 to 1.21. The sensitivity tests confirmed correlations between mild opioids and persistent non-cancer pain. Overall, while some models revealed a statistically significant positive correlation with 31 to 90 TSDs, this investigation found that cumulative opioid exposure below 90 TSDs was not consistently linked to an elevated risk of dementia.

Reference:

Pourhadi, N., Janbek, J., Gasse, C., Laursen, T. M., Waldemar, G., & Jensen-Dahm, C. (2024). Opioids and Dementia in the Danish Population. In JAMA Network Open (Vol. 7, Issue 11, p. e2445904). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2024.45904