OBJECTIVES: Cumulative anticholinergic burden (CAB) focuses on the cumulative effect of multiple medications with anticholinergic properties. However, concomitant use of cholinesterase inhibitors (ChEIs) and CAB can nullify the treatment benefit of ChEIs and worsen Alzheimer's disease (AD). This study evaluates the prevalence and factors associated with CAB among patients with AD initiating ChEIs.

METHODS: A retrospective longitudinal cohort study was conducted using the Medicare data from 2013-2017. The study included older adults ( >65 years) with a diagnosis of AD and incident ChEI (donepezil, rivastigmine, or galantamine) use. CAB was calculated based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using the defined daily dose over a one-year follow-up from ChEI initiation. CAB levels were dichotomized into moderate/high(Sum of standardized daily anticholinergic exposure over a year score ≥ 90) versus low/no (score 0–89). A multivariable logistic regression model was used to evaluate the factors associated with CAB based on the Andersen Behavioral Model.

RESULTS: The study included 222,064 older adults with AD with incident ChEI use (mean age 82.24 ±7.29, 68.9% females, 83.6% White). Overall, 80.48% had some anticholinergic burden, with most patients with moderate scores 90-500 (36.26%), followed by high scores >500 (24.76%), and low scores 1-89 (19.46%) burden categories. Predisposing factors such as age, males, African Americans, Asians, and Hispanics; need factors such as dyslipidemia, syncope, delirium, fracture, pneumonia, epilepsy, and claims-based frailty index were negatively associated with CAB. Positively associated enabling factors were dual eligibility and diagnosis year; need factors such as baseline burden, behavioral and psychological symptoms of dementia, depression, insomnia, urinary incontinence, irritable bowel syndrome, anxiety, muscle spasm, gastroesophageal reflux disease heart failure, and dysrhythmia.

CONCLUSIONS: Over 60% of older adults with AD had moderate-high CAB with several associated predisposing, enabling, and need factors. The study findings suggest a critical need to minimize CAB to improve AD care.