Table 1 Represents the summary of the included studies

Dubois [20]

France

multicenter double-blind, randomized, placebo controlled, parallel group study

18 months

Patients

were randomly assigned to two groups, to either active treatment or placebo [two capsules of 5 mg

donepezil (i.e., 10 mg) daily from week 6 to month 12; or placebo.

MCI

Donepezil group exhibited a statistically significant reduced rate of hippocampal atrophy compared with the placebo group There was no significant difference in neuropsychological

performance between treatment groups.

Hashimoto [21]

Japan

prospective cohort was compared with a

historical control cohort.

12 months

the patients received 3 mg/day of donepezil for 1 or 2 weeks

and then 5 mg/day

AD

Donepezil treatment slows

the progression of hippocampal atrophy,

suggesting a neuroprotective effect of

donepezil in Alzheimer’s disease.

Jack [22]

USA

randomized, double-blind, placebo-controlled,

parallel-group study

36 months

Participants were randomized into three groups: one received vitamin E, another received donepezil, and the third group received placebos, with all groups also taking a daily multivitamin.

MCI

Results of this study support the feasibility

of using MRI as an outcome measure of disease progression in multi center therapeutic trials for MCI.

Krishnan [23]

USA

randomized, double-blind, placebo-controlled,

parallel-group study was followed by a 6-week, single-blind placebo washout period.

24 weeks

Patients randomly assigned

to the donepezil group received 5 mg/day for the first 28 days and

10 mg/day thereafter.

AD

These preliminary results

suggest that donepezil may have a potentially protective effect in Alzheimer’s

disease.

Prins [24]

Netherlands

randomized, double-blind, placebo-controlled clinical trial

24 months

Patients were randomized

to receive galantamine or placebo for 24 months.

MCI

Patients with MCI who were treated with galantamine demonstrated a higher rate of hippocampal atrophy, compared to

placebo group.

Roman [25]

Canada

This investigation was a randomized, double-blind, placebo-controlled,

24 weeks

Participants were randomly assigned 2:1 to donepezil 5 mg or placebo

once daily.

Vascular Dementia

Patients treated with donepezil 5 mg/d demonstrated significant improvement in cognitive, but not global,

function.

Schuff [26]

USA

Subjects participated in a 3-week single-blind, placebo

run-in period followed by a 48-week double-blind period

51 weeks

they were randomly assigned to treatment

with 10 mg/day donepezil hydrochloride or placebo

MCI

These findings suggest a treatment effect of

donepezil on brain atrophy in aMCI.

Traini [27]

Italy

multicenter, randomized,

placebo-controlled, double-blind clinical trial

36 Months

Initially, the protocol plan was to treat patients either with donepezil + choline alphoscerate (treatment group D + CA) or donepezil + placebo (control group D + P) for 24 months

AD

Our findings indicate that the addition of choline alphoscerate to standard treatment with the cholinesterase

inhibitor donepezil counters to some extent the loss in volume occurring in some brain areas of AD patients combined with less pronounced cognitive impairment.

Moon [28]

Republic of Korea

-

24 weeks

Donepezil 10 mg

AD

donepezil-treated patients showed significantly increased volumes in the Hip, PCu, fusiform gyrus and caudate nucleus