Table 1.

Inclusion and exclusion criteria

Inclusion criteria

1. Outpatient with the capacity to give informed consent  2. Age 45 years or older  3. Diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorder and Stroke and Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria  4. Mini-Mental State Examination (MMSE) score of 10–30  5. An identified individual who can act as a reliable study partner to accompany the participant to all visits (face-to-face visits and telephone contact) and provide input into rating scales  6. On a stable dose of donepezil, galantamine or rivastigmine for the preceding 12 weeks  7. Fluency in English

Exclusion criteria

1. Labile blood pressure or new antihypertensive medication started within 3 weeks  2. Severe coronary insufficiency or myocardial infarction in the previous 6 months  3. History of unexplained syncope within the preceding 12 months  4. Cardiac conduction block  5. Severe hepatic impairment (ALT > 120, ALP > 390 and total bilirubin > 60)  6. Severe renal impairment (eGFR < 40)  7. Treatment with medications known to potentiate guanfacine’s hypotensive effects or cause arrhythmia (antipsychotics including sultopride, chlorpromazine, thioridazine, amisulpiride, sulpiride, haloperidol), moxifloxacin, baclofen, verapamil, quinidine, hydroquinidine, dispyramide, amiodarone, dofetilide, ibutilide, sotalol, pimazide, bepridil, casipride, diphemanil, erythromycin, halofantrine, pentamidine, sparfloxacin, vincamine, alfuzosin, prazosin, terazosin, tamsulosin and amifostine. Treatment with contradictions to guanfacine, see Appendix 1.  8. Weight under 45 kg (in order to ensure that an excessive dose per body weight is not used in the study)  9. Pregnancy (pre-menopausal women will only be entered into the study if they are surgically sterile or using effective birth control methods: these are abstinence for the period of the study, intrauterine contraception/device, male sexual partners with vasectomy)  10. History of severe chronic obstructive pulmonary disease (COPD) and/or asthma*

^*This exclusion criterion was added in August 2020 to reduce potential risk related to COVID-19