Tiotropium Use in COPD Linked to Minimal Risk for Dementia

TOPLINE:

The initiation of tiotropium monotherapy was associated with, at most, a modest increase in dementia risk among older adults with chronic obstructive pulmonary disease (COPD) compared with long-acting beta 2-agonist combined with inhaled corticosteroid (LABA-ICS) over a long-term follow-up, although the clinical significance of this finding remains uncertain.

METHODOLOGY:

• Researchers conducted a population-based cohort study using administrative data from Ontario, Canada, to examine whether the initiation of tiotropium monotherapy affects the risk for dementia in older adults with COPD.
• They included 30,960 new users of tiotropium monotherapy and compared them with 19,530 new users of LABA-ICS (mean age, 75.1 years; 46.7% women), all of whom had COPD without dementia and had started the medication from September 2004 through February 2012.
• The participants were followed up for a median of 7.59 years from the time of cohort entry.
• The study endpoint was incident dementia or censoring (death, insurance termination, or 10-year follow-up), whichever happened first.

TAKEAWAY:

• Compared with the initiation of LABA-ICS, tiotropium monotherapy was associated with a 9% higher risk for dementia (hazard ratio [HR], 1.09; 95% CI, 1.04-1.14).
• However, in the secondary as-treated analysis, the initiation of tiotropium was not associated with an increased risk for dementia compared with LABA-ICS (HR, 1.11; 95% CI, 0.93-1.32).
• Subgroup analysis revealed an 18% higher risk for dementia with tiotropium monotherapy vs LABA-ICS in adults younger than 75 years and a 12% higher risk in men.

IN PRACTICE:

“On balance, this evidence does not provide a compelling argument that patients with COPD should avoid tiotropium due to concerns about cognitive decline,” the authors of the study wrote.

SOURCE:

This study was led by Che-Yuan Wu, University of Toronto, Toronto, Ontario, Canada. It was published online on May 19, 2025, in JAMA Internal Medicine.

LIMITATIONS:

This study was potentially confounded by unmeasured factors such as smoking, dyspnea, peripheral biomarkers, spirometry measures, and other anticholinergic drugs. The assumption that the LABA-ICS comparator had no effect on the risk for dementia might not be true. The data for midlife medication dispensing and dementia biomarkers were unavailable.

DISCLOSURES:

This study was supported by the Heart-Brain Connection Brain-Heart Research Integrative Innovation Team Endeavor IMPACT Award from the Heart and Stroke Foundation of Canada, Brain Canada, and other sources. Few authors reported receiving financial support and grants from study funders and other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.