Efficacy and Safety of Donepezil in Chinese Patients with Severe Alzheimer’s Disease: A Randomized Controlled Trial

Abstract

Donepezil for 24 weeks was more effective than placebo and showed good safety and tolerability in Chinese patients with severe AD. This study supports utility of the drug in severe stages of AD in the Chinese population.

Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution

“…In a more recent study, the mean MMSE score of the population older than 90 years without dementia was reported to be 26.6, whereas the cutoff score for normal cognition was reported to be 23.3, very similar to the cutoff score for normal cognition in the younger population (~23 or 24 points) 62,63 . In the context of AD, the MMSE score is used to assess disease severity and is occasionally used to estimate efficacy in clinical drug trials 64 . Previous studies have shown that MMSE scores decrease during AD progression at different rates depending on disease progression and patient education 65 .…”

Clinical efficacy and safety of donepezil in the treatment of Alzheimer’s disease in Chinese patients

“…12 , 14 , 16 , 20 , 22 , 41 Lower dosage (5 mg/d) and shorter duration (12 or 16 weeks) in most of the above studies make Chinese AD patients on donepezil appear to have better safety and tolerability than the patients in the studies in Western countries and Japan (dropout rates 15%–32%, AE rates 37%–40%). 8 , 27 , 28 It has been further observed that donepezil at a dosage of 10 mg/d can be well tolerated in severe Chinese AD patients, 42 with a similar withdrawal rate (22.9% vs 10%–33.5%) and a lower AE rate (26.7% vs 80.6%) than Western severe AD studies. 10 , 39 , 43 – 45 The most common side effects of donepezil in Chinese AD patients, as shown in Table 2 , include dizziness, gastrointestinal symptoms (nausea, loss of appetite, vomiting, diarrhea, and constipation), insomnia, fatigue, sinus bradycardia, Q-T interval prolongation, abnormal liver function tests, and agitation.…”

“…Recently, a multicenter, double-blind, randomized, placebo-controlled study showed improvements in cognitive function and global function after 24-week treatment with donepezil in Chinese patients with severe AD, which facilitated the approval of donepezil for severe AD in China. 42 Compared to the results of a subgroup analysis from the moderate to severe AD study, 43 and a pooled data analysis 44 that includes a multinational study, 10 a Swedish nursing home study, 39 and a Japanese study 45 focusing on patients with severe AD, the mean treatment difference on Severe Impairment Battery (SIB) was 4.8 (Chinese study) vs 7.42 (post hoc analysis) vs 6.4 (pooled analysis), and the rate of improvement or no change on CIBIC-plus or Clinical Global Impression of Improvement was 74.7% vs 55.6% vs 70.8%, respectively. Effects on BPSD were not assessed in the Chinese study and were inconclusive from previous clinical trials.…”

A review of clinical treatment considerations of donepezil in severe Alzheimer's disease

“…Patients with moderate‐to‐severe AD who are recognized on a regimen of Aricept 10‐mg tablet daily for at least 3 months are candidates for dose escalation to Aricept 23‐mg tablet daily. Although statistically significant differences have been noted in cognition (a 2.2‐point improvement compared to the lower dosage of Aricept on the SIB 100‐point scale), no statistically significant differences were found in global functioning (a 0.06 improvement on the seven‐point CIBIC‐Plus scale) …”