The association between long-term opioid use and dementia risk: A systematic review and meta-analysis

Introduction: In recent years, the increasing use of opioids has raised significant concerns about their potential long-term effects on cognitive health, particularly in elderly and vulnerable populations. While opioids are widely prescribed for chronic pain management, evidence suggests that prolonged use may accelerate cognitive decline. Objective: This systematic review and meta-analysis aimed to investigate the association between opioid use and the risk of dementia. Methods: To identify relevant studies published, a comprehensive search was conducted across multiple databases, including PubMed, Scopus, and the Web of Science. Studies examining opioid exposure and subsequent dementia diagnosis were included. Two independent reviewers performed data extraction and quality assessment. Meta-analyses were conducted to assess pooled risk estimates. Results: Nine observational cohort studies were included. The random-effects model was applied. The pooled analysis showed a significant association between opioid use and an increased risk of dementia (HR = 1.35, 95 % CI = 1.21-1.50, P ≤0.0001). Subgroup analyses by geographical region showed consistent associations, with no significant differences between regions (P = 0.70). The P-value for Egger's test was 0.11, indicating no publication bias. Conclusion: These findings suggest that regular opioid use may be associated with a higher risk of dementia across the included studies; however, this finding should not be interpreted as evidence of causality. Clinicians should be aware of these potential risks when prescribing opioids, especially for older adults or those at higher risk of cognitive decline. Further research is needed to clarify underlying mechanisms and establish safe prescribing guidelines.