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Alzheimer Disease Treatment & Management

Updated: Jul 25, 2017
Author: Shaheen E Lakhan, MD, PhD, MS, MEd; Chief Editor: Jasvinder Chawla, MD, MBA
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TREATMENT

Treatment of Moderate to Severe Disease

The partial N-methyl-D-aspartate (NMDA) antagonist memantine (Namenda, Namenda XR) is
believed to work by improving the signal-to-noise ratio of glutamatergic transmission at the
NMDA receptor. Blockade of NMDA receptors by memantine is thought to slow the intracellular
calcium accumulation and thereby help prevent further nerve damage. This agent is approved
by the FDA for treating moderate and severe AD.

Several studies have demonstrated that memantine can be safely used in combination with
ChEIs. The combination of memantine with a ChEI has been shown to significantly delay
institutionalization in AD patients. [99] Studies suggest that the use of memantine with donepezil
affects cognition in moderate to severe AD [100] but not in mild to moderate AD. [101, 102] A once-
daily, fixed-dose combination of memantine extended-release (ER) and donepezil (Namzaric)
was approved by the FDA in 2014. [103] Dizziness, headache, and confusion are some of the
most common side effects of memantine.

In June 2013, the FDA approved rivastigmine transdermal for severe AD. [104] Approval was
based on the ACTION (ACTivities of Daily Living and CognitION in Patients with Severe
Dementia of the Alzheimer's Type) study, in which a higher dose of the drug (13.3 mg/24 hr)
demonstrated statistically significant improvement in overall cognition and function compared
with a lower dose (4.6 mg/24 hr). [105]