Abstract
The relationship between anticholinergics and early forms of cognitive impairment is not well defined. Our objective was to determine whether anticholinergic exposure influenced transitions in cognitive diagnosis among older adults with normal cognition or mild cognitive impairment (MCI) at baseline. We used data from an epidemiological study of the prevalence and course of MCI over time. Participants were 65 years or older recruited from a diverse primary care population in an urban health system in the US. Participants completed neuropsychologic assessment, informant interview, and full neurological and clinical exam with diagnosis defined by an expert panel at baseline and every 12 months. Transitions included normal cognition to MCI or dementia, and MCI to normal cognition or dementia. Anticholinergic use was defined by dose and duration fields of pharmacy dispensing and claims records to calculate cumulative exposure during each 12-month period. Logistic regression models with generalized estimating equations were used to compare transitions with stable diagnoses. The study was approved by the Institutional Review Board of IUPUI in Indianapolis. Among 350 participants, the mean age at baseline was 71 years, 79% were female and 62% were African American. Seventy-two percent used at least one mild anticholinergic medication. A total of 978 diagnostic assessments were completed: 221 (60.7%) with MCI were stable; 135 (37.1%) with MCI transitioned to normal; 8 (2.2%) with MCI transitioned to dementia; 511 (83.2%) with normal cognition were stable; and 103 (16.8%) with normal cognition transitioned to MCI. Compared to stable cognition, strong anticholinergic use increased the likelihood of transition from normal cognition to MCI after adjusting for age, gender, race, education, comorbidities, and APOE (odds ratio 1.34; 95% confidence interval: 1.04–1.74; p-value 0.0253). Compared to stable MCI, the odds ratio for the transition of MCI to normal showed a preventative trend among strong anticholinergic users, however this relationship was not statistically significant after similar adjustments (OR 0.92; 95% CI: 0.73–1.15; p-value 0.4675). Use of strong anticholinergic medications adversely influences cognitive diagnosis even in early stages of cognitive impairment. Interventions reducing anticholinergics should be tested to prevent or delay cognitive impairment.
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