Hong 2018.

Study characteristics
Methods	12‐week, multicentre, randomised, single‐blind, parallel group study
Participants	Setting: Neurology clinics of 3 university hospitals and 2 geriatric hospitals in South Korea Sample size: 67 patients were screened for eligibility, 65 were randomised to antidementia drug continuation group (N = 30) or antidementia drug discontinuation group (N = 35) Age: mean age = 81.3 ± 8.7 years (discontinuation) and 80.8 ± 7.4 years (continuation) Inclusion criteria 65‐100 years of age Diagnosis of dementia according to the DSM‐IV criteria Probable or possible AD according to the NINDS‐ADRDA criteria MMSE ≤ 5 Functional Assessment Staging (FAST) score of 6A or worse Ongoing donepezil or memantine therapy at a stable dose for at least 2 months Brain magnetic resonance imaging or computed tomographic scan showing no clinical evidence of other diseases (e.g. normal pressure hydrocephalus, brain tumour or cerebrovascular disease) capable of producing a dementia syndrome Knowledgeable and reliable caregiver sufficiently familiar with the patient to provide accurate information Exclusion criteria Primary neurodegenerative or psychiatric disorder other than AD (Parkinson's disease, schizophrenia or major depressive disorder) Severe or unstable medical disease that may prevent the patient from completing all study requirements (i.e. unstable or severe asthma or cardiovascular disease, active gastric ulcer, and severe hepatic or renal disease)
Interventions	The current use of donepezil or memantine was maintained at a stable dose during the 12‐week study period in the antidementia drug continuation group.The use of donepezil or memantine was discontinued during the study period after baseline in the antidementia drug discontinuation group. Patients were required to maintain medication with the potential to affect cognition (including anxiolytics, sedatives, hypnotics, antipsychotics and antidepressants) at a stable dose regimen for at least 30 days prior to screening and for the duration of the study.
Outcomes	1. Change from baseline on the Baylor Profound Mental State Examination (BPMSE) 2. MMSE 3. CGI‐C 4. CDR‐SB 5. NPI 6. CMAI 7. Barthel Index 8. ADCS‐ADL‐sev 9. FAST Efficacy assessments were performed at baseline (week 0) and the end of the study (week 12), and safety was monitored at all visits: weeks 0, 4, 8, and 12. All adverse events (AEs) and serious AEs were recorded at each study visit.
Source of funding	2012 Research Awards of Korean Society of Geriatric Neurology, Korea Healthcare Technology R&D Project, the Ministry of Health and Welfare South Korea, the Original Technology Research Program for Brain Science, National Research Foundation of Korea, Korean Government, Ildong Pharmaceutical Company Ltd.
Declaration of interest	All authors declared nothing to disclose
Notes	AD: Alzheimer's disease ADCS‐ADL‐sev: Alzheimer's Disease Cooperative Study ‐ Activities of Daily Living Inventory, modified for severe dementia BPMSE: Baylor Profound Mental State Examination CGI‐C: Clinical Global Impression of Change scale CDR‐SB: Clinical Dementia Rating Scale Sum of Boxes CMAI: Cohen Mansfield Agitation Inventory DSM‐IV: The Diagnostic and Statistical Manual of Mental Disorders Fourth Edition FAST: Functional Assessment Staging scale MMSE: Mini Mental State Examination NINCDS‐ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association NPI: Neuropsychiatric Inventory
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were randomly assigned in a 1:1 ratio to an ADD [antidementia drug]‐continuation group or an ADD‐discontinuation group by the block randomisation method using SAS [Statistical Analysis Software] and stratified according to current ADD (donepezil versus memantine)".
Allocation concealment (selection bias)	Low risk	"The randomisation sequence was known only to the clinical trial coordination center, which was contacted by the local principal investigator or co‐investigator at the participating center after enrollment of a patient".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and personnel were not blinded to treatment allocation. It is possible that the perception of the participants may be affected by their knowledge of the group to which they were assigned, therefore possibly indirectly affecting self‐reported measures such as, for example, side effects of drug withdrawal or rating of symptoms. Similarly, investigators involved in the care of the patient might have reminded them to be more aware of certain side effects of drug withdrawal. A higher rate of adverse events was reported in the ADD‐discontinuation group.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Outcome measures were assessed by raters who were unaware of group assignment. The same rater assessed outcome measures at baseline and the end of the study in each patient".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Of the 30 patients randomised to the ADD‐continuation group, 26 (86.7%) completed the study, while 30 of 35 patients (85.7%) allocated to the ADD‐discontinuation group completed. The difference in study withdrawal rates was not significant (P = 0.91). Study discontinuations due to adverse events (4/35, 11.4% versus 2/30, 6.7%, P = 0.51) and study discontinuations related to ADD usage or discontinuation (3/35, 8.6% versus 0/30, 0.0%, P = 0.10) were more frequent in the ADD‐discontinuation group than in the ADD‐continuation group, but the differences were not statistically significant. All deaths and serious adverse events were assessed by the investigators as not related to study medication or the study process. Primary and secondary efficacy analyses were based on the intention‐to‐treat (ITT) population using last‐observation‐carried‐forward (LOCF) imputation, where ITT was defined as randomised, dosed, with at least one outcome post‐randomisation. Per‐protocol (PP) analyses were also performed. Results of the ITT‐LOCF and PP analyses were similar.
Selective reporting (reporting bias)	Low risk	The study's specified outcomes were reported. Both ITT‐LOCF and PP analyses were reported as planned.
Other bias	Low risk	Appears to be free of other sources of bias