Summary of findings 2. Discontinued cholinesterase inhibitor compared to continued cholinesterase inhibitor in patients with dementia (medium‐term, 3‐11 months).

Discontinued cholinesterase inhibitor compared with continued cholinesterase inhibitor for patients with dementia (medium term, 3 to 11 months)
Patient or population: patients withdementia Settings: all healthcare settings Intervention: withdrawal of cholinesterase Inhibitor Comparison: continuation of cholinesterase Inhibitor
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Continued cholinesterase inhibitor	Discontinued cholinesterase inhibitor
Cognitive function (change from baseline, medium term) Standardised mean difference (SMMSE, MMSE)	‐	SMD 0.40 lower (0.87 lower to 0.09 higher; P = 0.10). Lower SMD means a greater decline in cognitive function from baseline	‐	411 (3)	⊕⊝⊝⊝ verylowa,b,c	It is uncertain whether discontinuing a ChEI reduces cognitive function compared to continuing treatment. The 95% confidence interval indicates that discontinuation might make little or no difference to cognitive function, and the certainty of the evidence is very low. On removing data from one study which only included participants who had shown a poor response to donepezil, inconsistency was reduced and the SMD was ‐0.62 (95% CI ‐0.94 to ‐0.31); P < 0.001.
Functional status (change from baseline, medium term) Standardised mean difference (BADLS, DAD)	‐	SMD 0.38 lower (0.74 lower to 0.01 lower; P = 0.04). Lower SMD means a greater decline in function from baseline	‐	314 (2)	⊕⊝⊝⊝ verylowd,e,f	It is uncertain whether discontinuing a ChEI may result in increased functional impairment compared to continuing ChEI treatment, because the certainty of the evidence is very low.
Neuropsychiatric status (change from baseline, medium term) Standardised mean difference (10 and 12‐item NPI)	‐	SMD 0.27 lower (0.47 lower to 0.08 lower; P = 0.007). Lower SMD means a greater deterioration in neuropsychiatric status from baseline	‐	410 (3)	⊕⊕⊝⊝ lowc,g	Discontinuation may result in increased neuropsychiatric symptoms compared to continuing ChEI treatment.
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BADLS: Bristol Activities of Daily Living Scale; ChEI: Cholinesterase inhibitor; CI: Confidence interval; DAD: Disability Assessment for Dementia Scale; MD: Mean Difference; MMSE: Mini‐Mental State Examination; NPI: Neuropsychiatric Inventory; OR: Odds Ratio; SMD: Standardised Mean Difference; SMMSE: Standardised Mini‐Mental State Examination
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.

^aSerious inconsistency: the confidence intervals did not all overlap, P = 0.005 and I² = 81%.
^bSerious imprecision: wide confidence interval including both no effect and a large effect
^cSerious risk of bias: one study had unclear risks of selection bias (allocation concealment), performance bias, detection bias, attrition bias and other bias, and one study had unclear risks of selection bias (allocation concealment), performance bias, detection bias, attrition bias and other bias, and high risk of reporting bias.
^dSerious imprecision: there were 314 participants in the two studies, and the upper confidence interval was close to the null effect value.
^eSerious inconsistency: I² = 60%
^fSerious risk of bias: one study had unclear risks of selection bias (allocation concealment), performance bias, detection bias, attrition bias and other bias, and high risk of reporting bias.
^gSerious imprecision: the CI includes essentially no effect, and an effect of moderate size, which may be clinically important.