Opioids do not carry increased risk of Alzheimer’s disease
Exposure to opioids does not appear to contribute to an increased risk of Alzheimer’s disease (AD), according to a study from Finland.
The nested case–control study included 70,718 individuals with AD, each of whom were matched with up to four comparison individuals. All participants were Finnish and with a clinically verified AD diagnosis during 2005 to 2011. Mean age of the cohort was 80 years, and majority (65 percent) were women.
Register-based data on opioid purchases, with the exception of codeine, were modelled into drug use periods using the PRE2DUP method. Cumulative opioid doses were converted to total standardized doses (TSDs). In the analyses, a 3-year time window between exposure (opioid use) and outcome (AD) was utilized to avoid reverse causality. Comorbid conditions and drug use were included as potential confounders.
Results showed no association between opioid use and increased risk of AD (adjusted odds ratio [OR], 1.00; 95 percent CI, 0.98 to 1.03). Furthermore, longer duration of use (cumulative use for >365 days: adjusted OR, 1.02; 0.96 to 1.08) and high cumulative doses (>90 TSDs: adjusted OR, 1.02; 0.98 to 1.07) of opioids were not related to the risk of AD.
Researchers pointed out that although an association was not observed between opioid use and risk of AD, additional studies should be conducted to evaluate the safety of long-term opioid use in terms of other cognitive effects.
Opioid medications are widely prescribed in older adults. Exposure to these drugs has been shown to be a risk factor for delirium, which is associated with greater risk of dementia risk, although the causal sequence is unclear. [J Am Geriatr Soc 2015;63:1519–1526]
Opioids exert a reversible effect on cognition by causing sedation. The drugs also modulate the behaviour of the immune cells in the brain that mediate inflammation, namely microglia, and this may contribute to the development of neurodegenerative diseases such as AD. Additionally, opioids promote apoptosis of microglia and neurons. [Brain 2010;133:3685-98; PLoS One 2011;6:e18190; Nat Rev Neurol 2010;6:193-201]