Methods
We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science,
and Clinical Trial Database Registry, particularly the Clinicaltrials.gov—
http://www.clinicaltrials.gov). We retrieved 173 references, which yielded three references for data extraction. A total of 3.574 subjects from four RCTs
were included in the meta-analysis. Among 1,784 subjects allocated in the ChEI-treatment group, 275 (15.4%) progressed to
AD/dementia, as opposed to 366 (20.4%) out of 1,790 subjects in the placebo group. The relative risk (RR) for progression
to AD/dementia in the ChEI-treated group was 0.75 [CI
95% 0.66–0.87],
z = −3.89,
P < 0.001. The patients on the ChEI group had a significantly higher all-cause dropout risk than the patients on the placebo
group (RR = 1.36 CI
95% [1.24–1.49];
z = 6.59,
P < 0.001). The RR for serious adverse events (SAE) in the ChEI-treated group showed no significantly statistical difference
from the placebo group (RR = 0.95 [CI
95% 0.83–1.09],
z = −0.72,
P = 0.47). The subjects in the ChEI-treated group had a marginally, non-significant, higher risk of death due to any cause
than those in the placebo-treated group (RR = 1.04, CI
95% 0.63–1.70,
z = 0.16,
P = 0.86).