Aim To investigate whether the inhibitory rate of serum butyrylcholinesterase (BuChE) activity in Japanese patients with Alzheimer's disease is correlated with cognitive function, behavioral symptoms and caregiver burden. Methods A total of 61 patients with mild to moderately severe Alzheimer's disease who were not undergoing cholinesterase enzyme inhibitor/memantine combinatorial treatment received a rivastigmine (18 mg) patch for 24 weeks. The rate of inhibition of BuChE was correlated with scores obtained on cognitive (Mini‐Mental State Examination), behavioral (the Japanese version of the modified Crichton Geriatric Behavioral Rating Scale [CGBRS] and Vitality Index [VI]) and burden (the Japanese version of Zarit Burden Inventory [ZBI]) scales; and the Clinical Global Impression of Change scale. Results The serum BuChE activity showed a significant decrease after 24 weeks compared with baseline (P < 0.001). Overall, significant effects were found in the Mini‐Mental State Examination score, VI score and modified CGBRS score. We then divided patient groups into a high inhibitory rate (≥40%) group and a low inhibitory rate (<40%) group; there were significant improvements in the Mini‐Mental State Examination score, VI score and modified CGBRS score in both groups. However, favorable results were seen in cooperation, restlessness and leisure on modified CGBRS subscales in the high inhibitory rate group (P < 0.001, P = 0.007, P < 0.001, respectively), and rehabilitation and other activities on VI subscales in the high inhibitory rate group (P = 0.005) compared with those in the low inhibitory rate group. Conclusions Demonstrable significant improvements in behavioral symptoms, such as low cooperation, restlessness or low activities in patients with Alzheimer's disease, were achieved on inhibition of BuChE at a rate of 40% or more. Geriatr Gerontol Int 2017; 17: 1306–1312.