Cholinesterase inhibitors in the treatment of dementia
- Daniel Press, MD
Daniel Press, MD
- Assistant Professor in Neurology
- Harvard Medical School
- Michael Alexander, MD
Michael Alexander, MD
- Professor of Neurology
- Harvard Medical School
- Section Editors
- Steven T DeKosky, MD, FAAN, FACP, FANA
Steven T DeKosky, MD, FAAN, FACP, FANA
- Section Editor — Dementia
- Professor of Neurology
- Deputy Director
- McKnight Brain Institute
- University of Florida College of Medicine
- Kenneth E Schmader, MD
Kenneth E Schmader, MD
- Editor in Chief — Geriatric Medicine
- Section Editor — Geriatrics
- Chief, Division of Geriatrics
- Duke University
- Director, Geriatric Research Education and Clinical Center
- Durham VA Medical Centers
Patients with Alzheimer disease (AD) have reduced cerebral production of choline acetyl transferase, which leads to a decrease in acetylcholine synthesis and impaired cortical cholinergic function. This early discovery of a marked cholinergic deficit in the brains of patients with AD led to the study of therapeutically augmenting cholinergic activity . However, acetylcholine precursors were found to be ineffective [2,3], while postsynaptic cholinergic receptor agonists had unacceptable side effects . By contrast, cholinesterase inhibitors, which increase cholinergic transmission by inhibiting cholinesterase at the synaptic cleft, have a more favorable side effect profile and are of some benefit in patients with AD as well as other non-AD dementias, albeit modest in most cases.
This topic will discuss the use of cholinesterase inhibitors in the treatment of dementia. Other treatments of dementia are discussed elsewhere. (See "Treatment of dementia".)
Three cholinesterase inhibitors, donepezil, rivastigmine, and galantamine, are currently approved for use in Alzheimer disease (AD) by the US Food and Drug Administration (FDA). The choice among the three available agents is based largely upon cost, individual patient tolerability, and physician experience, as efficacy appears to be similar (table 1) [5-7].
Donepezil — Donepezil has relatively little peripheral anticholinesterase activity and is generally well tolerated. This combined with its once-daily dosing has made it a popular drug in patients with AD. The recommended dose for donepezil is 5 mg per day for 4 weeks, then increasing to 10 mg per day. Donepezil is available in pill form and also as an oral disintegrating tablet for those unable or unwilling to swallow a pill.
The efficacy of donepezil was demonstrated in a 24-week double-blind study in which patients with mild to moderate AD were randomly assigned to donepezil (5 or 10 mg/day) or placebo . Cognition, as measured by the Alzheimer Disease Assessment Scale, cognitive subscale (ADAS-cog) , and the Clinician's Global Impression of Change (CGIC) ratings were significantly improved in both treatment groups compared with placebo. There was no consistent effect noted on patient-related quality of life measures.
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- ALZHEIMER DISEASE
- Advanced disease
- OTHER DEMENTIAS
- Vascular dementia
- Mixed dementia
- Dementia with Lewy bodies
- Parkinson disease
- Frontotemporal dementia
- Mild cognitive impairment
- Huntington disease
- Traumatic brain injury
- Multiple sclerosis
- PRACTICE ISSUES
- Degree of benefit
- Duration of therapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS