Figure 2. Dose Response of ChEIs Using Cubic Splines With (A) MMSE Change and (B) All-Cause Death Risk Compared With Nonuse.

Dose-response effect of increasing average cumulative daily dose of cholinesterase inhibitor (ChEI) compared to nonuse of ChEI: average (solid) and 95% confidence interval (dash lines). Horizontal axis represents the number of standard defined daily doses (DDDs) that patients took per day. For clarity, the DDD for each medication is shown with a vertical dotted line. For example, a patient taking galantamine 8 mg/d would be taking half the DDD of galantamine, which would be represented at the 0.5 point of the horizontal axis. In panel A, y-axis represents Mini-Mental State Examination (MMSE) score change. In panel B, y-axis represents adjusted hazard ratio for death. Model included ChEI treatment, visit time (class effect), interaction of ChEI treatment by visit, and baseline MMSE score. Reference was set at DDD 0. Cohort was matched for dementia diagnosis, age, sex, MMSE baseline score, comorbidity (hypertension, diabetes, myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, chronic obstructive pulmonary disease, renal disease, cancer, and atrial fibrillation), and medications (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blocking agents, calcium channel blockers, lipid-modifying agents, antipsychotics, and antidepressants).