Table 1 Summary of approved recommendations

• We recommend ChEIs as a treatment option for AD with cerebrovascular disease. (Grade 1B)

• We recommend ChEIs as a treatment option for dementia associated with Parkinson's disease. (Grade 1A)

• There is insufficient and inconsistent evidence on which to make a recommendation either for or against the use of the currently available ChEIs for the treatment of vascular dementia. (Grade 2B)

• All three ChEIs have demonstrated efficacy for mild to severe AD. We recommend a trial of a ChEIs for most patients with AD. (Grade 1A)

• Direct comparisons do not suggest differences between ChEIs (Grade 2B). Selection of which agent to be used will be based on the adverse effect profile, ease of use, familiarity, and differences between the agents in their pharmacokinetics and other mechanisms of action.

• There is insufficient evidence to recommend for or against the combination of a ChEI and memantine. (Grade 2B)

• Discontinuing ChEIs in patients with moderate to severe AD may lead to worsening of cognitive function and greater functional impairment as compared with continued therapy (Grade 2B). This risk must be balanced with the risk for known side-effects and drug costs if therapy continues. It is suggested that ChEIs be discontinued when:

   (i) the patient and/or their proxy decision-maker decide to stop after being appraised of the risks and benefits of continuation and discontinuation;

   (ii) the patient is sufficiently nonadherent with the medication that continued prescription of it would be useless, and it is not possible to establish a system for the administration of the medication to rectify the problem;

   (iii) the patient's rate of cognitive, functional, and/or behavioral decline is greater on treatment compared with that prior to being treated;

   (iv) the patient experiences intolerable side effects that are definitely or probably related to the ChEI;

   (v) the comorbidities of the patient make continued use of the agent either unacceptably risky or futile (for example, terminally ill); or

   (vi) the patient's dementia progresses to a stage (for example, Global Deterioration Scale stage 7) where there would be no clinically meaningful benefit from continued therapy.

• When a decision has been made to discontinue therapy because of a perceived lack of effectiveness, the suggestion is that the dose be tapered before stopping the agent and that the patient be monitored over the next 1 to 3 months for evidence of an observable decline. If this decline occurs, it is suggested that consideration be given to reinstating therapy. (Grade 2C)

• If the patient had an inadequate response to the nonpharmacological interventions or has a major depressive disorder, severe dysthymia or severe emotional lability, we recommend that a trial of an antidepressant could be considered. (Grade 2A)

• Based on good evidence we recommend that valproate should not be used for agitation and aggression in AD. (Grade 1A)

• There is insufficient evidence to recommend for or against the use of ChEIs and/or memantine for the treatment of neuropsychiatric symptoms as a primary indication. (Grade 2B)

• We recommend that risperidone, olanzapine and aripiprazole be used for severe agitation, aggression and psychosis associated with dementia where there is risk of harm to the patient and/or others. The potential benefit of all antipsychotics must be weighed against the significant risks, such as cerebrovascular adverse events and mortality. (Grade 2A)

• There is insufficient evidence to recommend for or against the use of quetiapine in the management of severe agitation, aggression and psychosis associated with dementia. (Grade 2B)

• There is insufficient evidence to recommend for or against the use of selective serotonin reuptake inhibitors or trazodone in the management of agitated patients. (Grade 2B)