Anticholinergics Influence Transition from Normal Cognition to Mild Cognitive Impairment in Older Adults in Primary Care

Abstract

Study objective: To determine the influence of anticholinergic medications on transitions in cognitive diagnosis of older adults in primary care.

Design: This observational cohort study was conducted over a mean follow-up of 3.2 years. Anticholinergic exposure was defined by pharmacy dispensing and claims records. Cognitive diagnosis was performed by an expert panel at baseline and annually up to 4 years.

Data source: Medication exposure and other clinical data were extracted from the Indiana Network for Patient Care (INPC). The cognitive diagnosis was derived from a cognitive screening and diagnosis study.

Participants: A total of 350 adults 65 years and older without dementia and receiving primary care in a safety net health care system.

Measurement and main results: Cognitive diagnosis followed a two-phase screening and consensus-based neuropsychiatric examination to determine a baseline diagnosis as normal cognition, mild cognitive impairment (MCI), or dementia, with a follow-up neuropsychiatric examination and consensus-based diagnosis repeated annually. The Anticholinergic Cognitive Burden scale was used to identify anticholinergics dispensed up to 10 years before enrollment and annually throughout the study. A total standard daily dose of anticholinergics was calculated by using pharmacy dispensing data from the INPC. Among 350 participants, a total of 978 diagnostic assessments were completed over a mean follow-up of 3.2 years. Compared with stable cognition, increasing use of strong anticholinergics calculated by total standard daily dose increased the odds of transition from normal cognition to MCI (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.31, p = 0.0342). Compared with stable MCI, strong anticholinergics did not influence the reversion of MCI to normal cognition (OR 0.95, 95% CI 0.86-1.05, p = 0.3266).

Conclusion: De-prescribing interventions in older adults with normal cognition should test anticholinergics as potentially modifiable risk factors for cognitive impairment.

Keywords: adverse drug reaction; anticholinergic; dementia; mild cognitive impairment; modifiable risk factors; pharmacoepidemiology; primary care.

Figure 1

Timeline for collection of cognitive outcome and exposure variables.

Figure 2

Calculation of total standard daily dose (TSDD) for strong anticholinergic exposure. Anticholinergic exposure using all anticholinergics (mild, possible, and strong with scores 1, 2, and 3, respectively) included a multiplier corresponding to the score for each medication in the numerator.