Objective: Mild behavioral impairment (MBI) is a syndrome of late-life-onset persistent neuropsychiatric symptoms. Anticholinergic medication is commonly prescribed in older adults. Both MBI and anticholinergic exposure are associated with increased dementia risk. We sought to understand the association of anticholinergic burden (ACB) with MBI.

Design, setting, participants: We mapped ratings on the Neuropsychiatric Inventory Questionnaire to the MBI checklist (MBI-C) using an established algorithm to define MBI status in cognitively unimpaired individuals in the National Alzheimer's Coordinating Center database. We then assessed the association between time-varying ACB ratings and risk of incident MBI.

Results: 4865 participants met inclusion criteria and were followed for a mean (SD) of 5.64 (3.92) years. ACB scores ranged from 0 to 11. 63.3% of participants had a score of 0, 27.7% had a score of 1-2, and 9% had a score of ≥3. Higher maximum total ACB score was associated with a higher likelihood of developing MBI (p ≤0.001). When assessed as a time varying covariate, ACB score was associated with incident MBI (HR 1.07, 95% CI 1.02-1.14, p = 0.010). This association remained significant when adjusted for 10-year mortality risk, age, sex, education, and race.

Conclusions: MBI risk should be considered when prescribing anticholinergic medication in older adults.