OBJECTIVES: Acetylcholinesterase inhibitors (AChEIs) may counteract the anticholinergic properties of certain atypical antipsychotics (AAs) and thereby affect the adverse outcomes in dementia patients. This study evaluated the risk of falls and fractures due to the concomitant use of AChEIs and AAs (classified as high-level versus low-level anticholinergic) among older adults with dementia.

METHODS: This retrospective cohort study included older adults (aged>=65 years) with a diagnosis of dementia identified using ICD-9-CM codes, and multi-year (2013-2015) Medicare claims data involving Parts A, B, and D. The study identified new users of AChEIs who used AAs concomitantly, and followed them for up to 180 days for occurrence of falls/fractures. AAs were classified into high-level (e.g. olanzapine, quetiapine) and low-level (e.g. risperidone, aripiprazole, etc.) anticholinergics based on the Anticholinergic Drug Scale. Descriptive statistics examined the demographic and clinical characteristics of the cohort. Multivariable Cox proportional hazards regression with inverse probability of treatment weighting (IPTW) compared risk of falls/fractures among high-level versus low-level anticholinergic AAs users with concomitant AChEIs use.

RESULTS: The study identified 12,573 older adults with dementia, who were concomitant users of AChEIs and AAs. Most were females (67.60%), white (84.47%), aged between 85-94 years (41.16%). There were 8,149 (64.81%) high-level anticholinergic AA users, and 4,424 (35.19%) low-level anticholinergic AA users. A total of 1,978 (24.27%) high-level anticholinergic AA users, and 1,111 (25.11%) low-level anticholinergic AA users encountered falls/fractures during the follow-up period. The Cox regression with IPTW found no statistically significant difference (aHR=1.06; 95% CI, 0.94-1.18) between high-level and low-level anticholinergic AA users with concomitant AChEIs use for the risk of falls/fractures.

CONCLUSIONS: The study found no significant difference in the risk of falls/fractures among users of high-level versus low-level anticholinergic AAs with concomitant AChEIs use. AChEIs seem to counteract the adverse effects of high-level and low-level anticholinergic AAs in dementia.