Alzheimer Disease Medication

Updated: Jul 07, 2023
  • Author: Shaheen E Lakhan, MD, PhD, MS, MEd, FAAN; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Medication

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. 

As of early 2023, two anti-amyloid beta monoclonal antibodies (ie, aducanumab, lecanemab) are available in the United States. [100, 101] Lecanemab has gained full approval from the FDA. Aducanumab is available via accelerated approval and continued approval is contingent upon verification of clinical benefit in a confirmatory trial. Anti-amyloid beta monoclonal antibodies may potentially be the first disease-modifying therapy for AD. 

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Cholinesterase Inhibitors

Class Summary

Cholinesterase inhibitors (ChEIs) are used to palliate cholinergic deficiency. All 4 currently approved ChEIs (ie, donepezil, rivastigmine, galantamine) inhibit acetylcholinesterase (AChE) at the synapse (specific cholinesterase).

Rivastigmine also inhibits butyrylcholinesterase (BuChE). Although BuChE levels may be increased in AD, it is not clear that rivastigmine has 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.

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.

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 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.

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.

Donepezil transdermal (Adlarity)

Donepezil transdermal is a reversible acetylcholinesterase inhibitor. It is the first patch to continuously deliver consistent doses of donepezil through the skin. The FDA approved the transdermal system for the treatment of mild, moderate, or severe Alzheimer dementia.

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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.

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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Combination Drugs

Class Summary

Combination products may aid in ease of administration (decreased pill burden) and enhance compliance.

Memantine/donepezil (Namzaric)

Fixed dose combination capsule containing memantine extended-release and donepezil for patients with moderate-to-severe Alzheimer disease currently stabilized on donepezil 10 mg once daily. Administer once daily in the evening. Memantine is a NMDA receptor antagonist and donepezil is an acetylcholinesterase inhibitor.

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Monoclonal Antibodies, Anti-amyloid Beta

Class Summary

Monoclonal antibodies are being developed that targets beta amyloid and binds to aggregated forms of beta-amyloid to reduce plaques associated with Alzheimer disease.

Lecanemab (Leqembi)

Humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. It is indicated for treatment of patients with Alzheimer disease who have mild cognitive impairment or mild dementia stage disease. 

Aducanumab (Aduhelm)

Aducanumab is a high affinity, fully human IgG1 monoclonal antibody that targets beta amyloid and binds to aggregated forms of beta amyloid; preferentially binds to parenchymal over vascular amyloid. The FDA granted accelerated approval for aducanumab based on reduction in amyloid beta plaques observed in patients treated for Alzheimer disease. The prescribing information specifies approval for patients with mild cognitive impairment or a mild dementia stage of disease, the population studied in the clinical trials. 

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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.

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.

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.

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.

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.

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