Anticholinergic drugs and risk of dementia: case-control study04 Jun 2018
OBJECTIVES: To estimate the association between duration and level of exposure to different classes of anticholinergic medication and subsequent incident dementia. DESIGN: Case-control study SETTING: General practices in the United Kingdom contributing to the Clinical Practice Research Datalink. PARTICIPANTS: 40,770 patients aged 65-99 years and diagnosed with dementia between April 2006 and July 2015, and 283,933 controls without dementia matched 7:1 on date, sex, age, level of deprivation of the area in which each practice is located, and years of available data history. INTERVENTIONS: Daily defined doses (DDD) of anticholinergic medications coded according to the Anticholinergic Cognitive Burden (ACB) scale; in total and grouped by subclass; prescribed between 4-20 years prior to dementia diagnosis. MAIN OUTCOME MEASURES: Odds ratios for incident dementia, adjusted for a wide range of demographics and health-related covariates. RESULTS: 14,453 (35%) cases and 86,403 (30%) controls were prescribed at least one definite (ACB score 3, ACB3) anticholinergic during the exposure period. The adjusted odds ratio (aOR) for ‘any ACB3’ was 1.11 (95% confidence interval 1.08 to 1.14), and an increasing odds of dementia was significantly associated with an increasing average ACB score. When considered by class, ACB3 gastro-intestinals were not significantly linked to dementia. Within ACB3 antidepressants, urologicals, and antiparkinson medications, risks increased with greater exposure, and was still observed for exposure 15-20 years before diagnosis. CONCLUSIONS: In the largest study to date, a robust association between some classes of anticholinergic medication use and future dementia incidence was observed. This could be caused by a class-specific effect, or by medications being used for very early symptoms of dementia. Future pharmacological and clinical research should examine subgroups of anticholinergics as opposed to anticholinergic effects per se or summing scales for anticholinergic exposure.