Regular Use of Strong Opioids May Lead to Increased Dementia Risk

The regular use of opioids, particularly strong opioids, is associated with an increased risk for dementia among patients with chronic noncancer pain, according to study results published in Alzheimer’s & Dementia.

Researchers conducted a prospective study to evaluate the association between regular opioid use and the risk for incident dementia, as well as potential opioid-related neurobiologic differences among patients with chronic noncancer pain. The researchers sourced data from the United Kingdom (UK) Biobank. Patients were categorized into 3 groups: no analgesic use; nonopioid analgesic use; and opioid use, with opioids further classified as weak or strong based on potency. Incident diagnoses of dementia were tracked over a mean follow-up of 13.8 years. Neuroimaging (magnetic resonance imaging [MRI]) and cognitive assessments (fluid intelligence, prospective memory) were conducted in subsamples of UK Biobank patients. Cox, linear, and logistic regression were employed for statistical analysis.

Among 197,673 patients with chronic noncancer pain, 11.2% reported regular opioid use (94.7% weak opioids; 5.3% strong opioids). Nearly half (44.3%) of patients used nonopioid analgesics or no analgesics (44.5%). Patients who reported opioid use were generally older, and a greater percentage were women and current smokers. Compared with patients who did not report opioid use, those who reported opioid use also had a higher number of chronic pain conditions and comorbidities as well as greater use of glucocorticoids, anticholinergics, and acetylsalicylic acid.

During follow-up, regular opioid use was associated with an increased risk for all-cause dementia (adjusted hazard ratio [aHR], 1.20; 95% CI, 1.07-1.33), vascular dementia (aHR, 1.49; 95% CI, 1.22-1.83), and Alzheimer disease (AD; aHR, 1.15; 95% CI, 0.98-1.35). Compared with nonuse of analgesics, use of weak opioids was associated with an increased risk for all-cause dementia (aHR, 1.18; 95% CI, 1.05-1.31) and vascular dementia (aHR, 1.45; 95% CI, 1.18-1.78). Use of strong opioids vs nonuse of opioids was linked to an even higher risk for all-cause dementia (aHR, 1.72; 95% CI, 1.22-2.44) and vascular dementia (aHR, 2.55; 95% CI, 1.46-4.44). Use of nonopioid analgesics showed no significant associations with AD.

Among 14,538 patients with MRI data, strong opioid use was significantly associated with reduced total brain volume (β=-0.39; 95% CI, -0.69 to -0.09), white matter volume (β=-0.47; 95% CI, -0.82 to -0.12), and hippocampal volume (β=-0.62; 95% CI, -0.96 to -0.28), whereas no associations were seen for weak opioids or nonopioid analgesics.

In cognitive testing of 19,612 patients, opioid use was associated with lower fluid intelligence scores (β=-0.18; 95% CI, -0.31 to -0.05), particularly weak opioids (β=-0.17; 95% CI, -0.31 to -0.04). No significant differences were found for prospective memory across any group, and no significant association was found for use of nonopioid analgesics and fluid intelligence. Sensitivity analyses, including competing risk models and multiple imputation, confirmed the robustness of these findings.

Limitations of this study include its reliance on self-reported opioid use without detailed information on baseline dose, duration, or indication; its lack of pain-specific clinical data such as pain severity or nondrug treatments, which may introduce residual confounding; and use of administrative “first occurrence” data to identify dementia, which includes some self-reported cases.

The researchers concluded, “The association between regular opioid use, especially potent opioids, and dementia should be considered when managing CNCP [chronic noncancer pain].”

This article originally appeared on Clinical Pain Advisor