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Alzheimer Disease Medication

Author: Heather S Anderson, MD; Chief Editor: Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA
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Updated: Jul 28, 2014

Medication Summary
The mainstay of therapy for patients with Alzheimer disease (AD) is the use of centrally acting cholinesterase
inhibitors to attempt to compensate for the depletion of acetylcholine (ACh) in the cerebral cortex and hippocampus.
A partial N -methyl-D-aspartate (NMDA) antagonist is approved for treatment of moderate and severe AD. Various
medications are used for treatment of secondary symptoms of AD, including antidepressants, anti-anxiety agents,
and antipsychotic agents.

Cholinesterase Inhibitors
Class Summary
Cholinesterase inhibitors (ChEIs) are used to palliate cholinergic deficiency. All 4 currently approved ChEIs (ie,
tacrine, donepezil, rivastigmine, galantamine) inhibit acetylcholinesterase (AChE) at the synapse (specific
cholinesterase). Tacrine was the first agent that was approved for AD, but because of its potential to cause
hepatotoxicity, it is now rarely used.

Tacrine and rivastigmine also inhibit butyrylcholinesterase (BuChE). Although BuChE levels may be increased in AD,
it is not clear that rivastigmine and tacrine have greater clinical efficacy than donepezil and galantamine.

Galantamine has a different second mechanism of action; it is also a presynaptic nicotinic modulator. No data exist
to indicate that this second mechanism is of clinical importance.

View full drug information

Donepezil (Aricept, Aricept ODT)

Donepezil is indicated for the treatment of dementia of the Alzheimer type. Donepezil has shown efficacy in patients
with mild to moderate AD, as well as moderate to severe AD. It selectively inhibits acetylcholinesterase, the enzyme
responsible for the destruction of acetylcholine, and improves the availability of acetylcholine. Donepezil's long half-
life provides a long duration of drug availability for binding at the receptor sites. There is no evidence to suggest that
the underlying disease process of dementia is affected by administration of donepezil.

Dosing recommendations for mild to moderate AD are 5-10 mg given once daily. Patients with moderate to severe
AD can be given 10 or 23 mg once daily.

View full drug information

Rivastigmine (Exelon, Exelon Patch)

Rivastigmine PO is indicated for the treatment of mild to moderate dementia of the Alzheimer type. Initial dosing
recommendations are 1.5 mg PO BID, with a maximum dose of 12 mg/day PO. Rivastigmine is a potent, selective

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inhibitor of brain AChE and BChE. Rivastigmine is considered a pseudo-irreversible inhibitor of AChE.

While the precise mechanism of rivastigmine's action is unknown, it is postulated to exert its therapeutic effect by
enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through
reversible inhibition of its hydrolysis by cholinesterase.

The transdermal patch 13.3 mg/24 h is approved for all stages of Alzheimer disease, including severe. Dose titration
is needed when initiating.

View full drug information

Galantamine (Razadyne, Razadyne ER)

Galantamine is indicated for the treatment of mild to moderate dementia of the Alzheimer type. It enhances central
cholinergic function and likely inhibits AChE. There is no evidence that galantamine alters the course of the
underlying dementing process. The dosing recommendation for the immediate-release formulation is 4 mg twice
daily. The extended-release formulation is given at a dose of 8 mg once daily. The maintenance dose after dose
titration is 16-24 mg/day.

View full drug information

Tacrine

Tacrine was the first agent approved for AD. It is indicated in patients with mild to moderate dementia. It is
associated with hepatotoxicity and is no longer commonly used. Tacrine inhibits AChE, the enzyme responsible for
the destruction of acetylcholine, and improves the availability of acetylcholine. Tacrine inhibits both AChE and BChE;
however, it is more selective for AChE.

N-Methyl-D-Aspartate Antagonists
Class Summary
The only drug in the N -methyl-D-aspartate (NMDA) antagonist class that is approved by the US Food and Drug
Administration is memantine. This agent may be used alone or in combination with AChE inhibitors.

View full drug information

Memantine (Namenda, Namenda XR)

Namenda is approved for the treatment of moderate to severe dementia in patients with AD. The initial dose for the
immediate-release formulation is 5 mg once daily, and it can be titrated to a maximum dose of 20 mg/day. The initial
dose for the extended-release formulation is 7 mg once daily, and it can be titrated to a maximum dose of 28
mg/day.

Nutritional Supplement
Class Summary

Medical foods are dietary supplements intended to compensate specific nutritional problems caused by a disease or
condition. Caprylidene is a prescription medical food that is metabolized into ketone bodies. The brain can use these
ketone bodies for energy when its ability to process glucose is impaired, which brain-imaging scans suggest is the
case in AD.

View full drug information

Caprylidene (Axona)

Caprylidene is indicated for clinical dietary management of metabolic processes associated with mild to moderate
AD. General dosing recommendations include administering 40 g/day (1 packet of caprylidene powder, containing 20
g of medium-chain triglycerides) during breakfast.
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Diagnostic Imaging Agents

Class Summary

Imaging agents that bind to beta amyloid plaque may be useful in the diagnosis of early onset dementia.

View full drug information

Florbetapir F 18 (AMYViD)

Radioactive diagnostic agent for use with PET brain imaging. Binds to beta-amyloid neuritic plaques and the F 18
isotope produces a positron signal that is detected by a PET scanner.

View full drug information

Flutemetamol F 18 (Vizamyl)

Flutemetamol F18 is a radioactive diagnostic agent for use with PET brain imaging. It binds to beta-amyloid neuritic
plaques, and the F18 isotope produces a positron signal that is detected by a PET scanner.

View full drug information

Florbetaben F 18 (Neuraceq)

Flutemetamol F18 is a radioactive diagnostic agent for use with PET brain imaging. It binds to beta-amyloid neuritic
plaques, and the F18 isotope produces a positron signal that is detected by a PET scanner.

Contributor Information and Disclosures

Author
Heather S Anderson, MD Associate Professor, Staff Neurologist, Department of Neurology, University of
Kansas Alzheimer's Disease Center

Heather S Anderson, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Chief Editor
Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA Professor of Neurology, University of Central Florida
College of Medicine; Director of Cognitive Neurology, Director of Stroke Program, James A Haley Veterans Affairs
Hospital

Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA is a member of the following medical societies:
American Academy of Neurology, American Headache Society, American Heart Association, and American
Society of Neuroimaging

Disclosure: Nothing to disclose.

Additional Contributors
Guy E Brannon, MD Associate Clinical Professor of Psychiatry, Louisiana State University Health Sciences
Center; Director, Adult Psychiatry Unit, Chemical Dependency Unit, Clinical Research, Brentwood Behavior
Health Company

Guy E Brannon, MD is a member of the following medical societies: American Medical Association, American
Medical Writers Association, American Psychiatric Association, American Society of Addiction Medicine,
Association of Clinical Research Professionals, Louisiana State Medical Society, and Southern Medical
Association

Disclosure: AstraZeneca Grant/research funds Other; Janssen Grant/research funds Other; Pfizer Honoraria
Speaking and teaching; Sunovion Honoraria Speaking and teaching; Eli Lilly Grant/research funds Other; Forrest
Grant/research funds Other

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Linda P Boswell, MD Medical Director of Senior Care Unit, Bossier Medical Center; Private Practice, Shreveport,
Louisiana

Linda P Boswell, MD is a member of the following medical societies: American Medical Association, American
Psychiatric Association, and Louisiana State Medical Society

Disclosure: Nothing to disclose.

Jody L Haddock, MD Resident Physician, Department of Internal Medicine, University of Tennessee College of
Medicine Chattanooga

Disclosure: Nothing to disclose.

Rodrigo O Kuljis, MD Esther Lichtenstein Professor of Psychiatry and Neurology, Director, Division of Cognitive
and Behavioral Neurology, Department of Neurology, University of Miami School of Medicine

Rodrigo O Kuljis, MD is a member of the following medical societies: American Academy of Neurology and
Society for Neuroscience

Disclosure: Nothing to disclose.

Alan D Schmetzer, MD Professor, Vice-Chair for Education, Assistant Training Director in General Psychiatry
and Director of Residency Training in Addiction Psychiatry, Department of Psychiatry, Indiana University School of
Medicine

Alan D Schmetzer, MD, is a member of the following medical societies: American Academy of Addiction
Psychiatry, American Academy of Clinical Psychiatrists, American Academy of Psychiatry and the Law, American
College of Physician Executives, American Medical Association, American Neuropsychiatric Association,
American Psychiatric Association, and Association for Convulsive Therapy

Disclosure: Eli Lilly & Co. Grant/research funds Other

Ronald Schneider, MD Chief Medical Officer, Mental Health Outreach Program, Overton Brooks Veterans Affairs
Medical Center; Clinical Assistant Professor of Psychiatry, Louisiana State University Health Sciences Center

Ronald Schneider, MD is a member of the following medical societies: American Psychiatric Association and
Louisiana Psychiatric Medical Association

Disclosure: Pfizer Honoraria Speaking and teaching; Janssen Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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