Alzheimer Disease Medication

  • Author: Heather S Anderson, MD; Chief Editor: Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA   more...
 
Updated: Apr 12, 2012
 

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.

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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.

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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.

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Rivastigmine (Exelon, Exelon Patch)

 

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

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Contributor Information and Disclosures
Author

Heather S Anderson, MD  Assistant Professor, Staff Neurologist, Department of Neurology, Alzheimer and Memory Center, University of Kansas Medical 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

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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Amyloid plaques. Image courtesy of NIH
APP is associated with the cell membrane, the thin barrier that encloses the cell. After it is made, APP sticks through the neuron's membrane, partly inside and partly outside the cell. Image courtesy of NIH.
Enzymes (substances that cause or speed up a chemical reaction) act on the APP and cut it into fragments of protein, one of which is called beta-amyloid. Image courtesy of NIH.
The beta-amyloid fragments begin coming together into clumps outside the cell, then join other molecules and non-nerve cells to form insoluble plaques. Image courtesy of NIH.
Healthy neurons. Image courtesy of NIH.
Image courtesy of NIH.
Preclinical Alzheimer disease. Image courtesy of NIH.
Mild Alzheimer disease. The disease begins to affect the cerebral cortex, memory loss continues, and changes in other cognitive abilities emerge. The clinical diagnosis of AD is usually made during this stage. Image courtesy of NIH.
Severe Alzheimer disease. In the last stage of AD, plaques and tangles are widespread throughout the brain, and areas of the brain have atrophied further. Patients cannot recognize family and loved ones or communicate in any way. They are completely dependent on others for care. All sense of self seems to vanish. Image courtesy of NIH.
Preclinical Alzheimer disease. Image courtesy of NIH.
Mild-to-moderate Alzheimer disease. Image courtesy of NIH.
Severe Alzheimer disease. Image courtesy of NIH.
Cortical atrophy with hydrocephalus ex vacuo is seen in Alzheimer disease.
Plaques and tangles in Alzheimer disease.
Amyloid angiopathy in Alzheimer disease.
Coronal T1-weighted magnetic resonance imaging (MRI) scan in a patient with moderate Alzheimer disease. Brain image reveals hippocampal atrophy, especially on the right side.
Table 1. DSM-IV-TR Diagnostic Criteria for Dementia of the Alzheimer Type
A. The development of multiple cognitive deficits manifested by both of the following:



  • Memory impairment (impaired ability to learn new information or to recall previously learned information)
  • One or more other cognitive disturbances: aphasia (language disturbance), apraxia (impaired ability to carry out motor activities despite intact motor function), agnosia (failure to recognize or identify objects despite intact sensory function), disturbance of executive functioning
B. The cognitive deficits must each cause significant impairment in social or occupational function and represent a significant decline from a previous level of functioning.



C. The course of disease is characterized by gradual onset and continuing decline.



D. The cognitive deficits are not due to any of the following:



  • Other central nervous system conditions that cause progressive deficits in memory and cognition
  • Systemic conditions that are known to cause dementia
  • Substance-induced conditions
E. The deficits do not occur exclusively during the course of a delirium.



F. The disturbance is not better accounted for by another DSM-IV Axis I disorder (ie, a clinical disorder).



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