Psych · Psychopharmacology — cognitive enhancers
Cognitive enhancers (cholinesterase inhibitors and memantine)
Also known as Cholinesterase inhibitors · AChEI · Donepezil · Rivastigmine · Galantamine · Memantine · Anti-dementia drugs · Cognitive enhancers dementia
Exam-exhaustive fellowship monograph on cholinesterase inhibitors and memantine — mechanisms, severity- and subtype-linked indications (AD, DLB, PDD, MCI caveats), adult oral and patch doses with titration and monitoring, DOMINO-AD continuation, combination therapy, AD2000 appraisal, cardiac/GI safety, deprescribing, and BAP/APA/NICE-style regional framing. FRANZCP-primary, globally tagged.
Practise this topic
On this page
Study tools
Your progress
Saved on this device.
Target exams
Red flags
- Syncope, marked bradycardia, or new conduction block on a cholinesterase inhibitor — hold drug, ECG, medical review
- Severe vomiting, dehydration, or suspected GI bleed after AChEI start or uptitration — stop and investigate
- Rapid functional collapse after abrupt AChEI withdrawal — consider restart if goals of care still support treatment (DOMINO-AD lens)
- Memantine accumulation risk in significant renal impairment without dose adjustment
- Prescribing AChEI for pure MCI as if disease-modifying standard of care
- Promising cure or disease modification — these agents are symptomatic only
Meet the patient
A 78-year-old retired engineer has had Alzheimer disease for four years. His MMSE has drifted into the moderate–severe range. He has done well on donepezil 10 mg, but the team on the ward round asks whether it is "time to stop it, given how advanced he is". His wife says the tablet is "the one thing that keeps him himself".[7][18]
The exam question this vignette plants is the one registrars get wrong by reflex: does worsening severity mandate stopping the cholinesterase inhibitor? DOMINO-AD says no — not automatically. This topic is the prescribing spine behind that answer, with the doses, the subtypes and the stop rules intact.[7][13][18]
References20ShowHide
- [1]Rogers SL, Farlow MR, Doody RS, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease Neurology, 1998.PMID 9443470
- [2]Feldman H, Gauthier S, Hecker J, et al. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease Neurology, 2001.PMID 11524468
- [3]Rösler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial BMJ, 1999.PMID 10066203
- [4]Tariot PN, Solomon PR, Morris JC, et al. A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group Neurology, 2000.PMID 10881251
- [5]Reisberg B, Doody R, Stöffler A, et al. Memantine in moderate-to-severe Alzheimer's disease N Engl J Med, 2003.PMID 12672860
- [6]Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial JAMA, 2004.PMID 14734594
- [7]Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease N Engl J Med, 2012.PMID 22397651
- [8]Courtney C, Farrell D, Gray R, et al. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial Lancet, 2004.PMID 15220031
- [9]McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study Lancet, 2000.PMID 11145488
- [10]Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinson's disease N Engl J Med, 2004.PMID 15590953
- [11]Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment N Engl J Med, 2005.PMID 15829527
- [12]Tricco AC, Soobiah C, Berliner S, et al. Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis CMAJ, 2013.PMID 24043661
- [13]Birks JS, Harvey RJ Donepezil for dementia due to Alzheimer's disease Cochrane Database Syst Rev, 2018.PMID 29923184
- [14]Birks JS, Chong LY, Grimley Evans J Rivastigmine for Alzheimer's disease Cochrane Database Syst Rev, 2015.PMID 26393402
- [15]McShane R, Westby MJ, Roberts E, et al. Memantine for dementia Cochrane Database Syst Rev, 2019.PMID 30891742
- [16]Winblad B, Grossberg G, Frölich L, et al. IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease Neurology, 2007.PMID 17646619
- [17]Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline Ann Intern Med, 2008.PMID 18316756
- [18]O'Brien JT, Holmes C, Jones M, et al. Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology J Psychopharmacol, 2017.PMID 28103749
- [19]Rabins PV, Blacker D, Rovner BW, et al. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. Second edition Am J Psychiatry, 2007.PMID 18340692
- [20]Holmes C, Wilkinson D, Dean C, et al. The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease Neurology, 2004.PMID 15277611