Medications for cognitive symptoms
The U.S. Food and Drug Administration (FDA) has approved two types of medication to treat cognitive symptoms of Alzheimer’s disease: (1) cholinesterase inhibitors and (2) memantine. Clinical trials have shown both to offer modest benefit in cognition and overall function, but neither is known to affect underlying brain deterioration.
1. Cholinesterase inhibitors
Alzheimer’s disease has a devastating impact on the brain’s cholinergic system. This cell network is critical for learning and memory. Cholinesterase inhibitors increase the availability of acetylcholine, a key chemical messenger in the cholinergic system. Specifically, the inhibitors block the activity of acetylcholinesterase, the chief enzyme that breaks acetylcholine down.
Increased acetylcholine levels temporarily improve function in the cholinergic system. Ultimately, however, the drugs cannot reverse the steady loss of cholinergic neurons caused by Alzheimer’s. Clinical research has found that cholinesterase inhibitors postpone the worsening of Alzheimer's symptoms for an average of six months to a year.
The most commonly prescribed cholinesterase inhibitors are:
- Donepezil (Aricept)
- Rivastigmine (Exelon)
- Galantamine (Razadyne)
All three are approved for mild-to-moderate Alzheimer's stages. Donepezil is also approved for severe stages.
The most common side effects of these drugs are nausea, diarrhea and insomnia.
Memantine is classified as an N-methyl-D-aspartate (NMDA) receptor antagonist. It appears to work by regulating the activity of glutamate, a chemical messenger that plays an essential role in learning and memory.
Glutamate triggers proteins called NMDA receptors to allow a controlled amount of calcium into a nerve cell. Regulated calcium levels are required for the brain to store information properly. Excess glutamate, on the other hand, overstimulates NMDA receptors to allow too much calcium into nerve cells. This problem leads to a disruption of cell-to-cell communication and cell death in the brain. Memantine may protect cells against excess glutamate by partially blocking NMDA receptors.
Memantine is currently approved for people with moderate-to-severe Alzheimer’s disease, but not for those with mild Alzheimer’s. Clinical studies have found the drug may offer a modest benefit in patient memory, daily activity and overall function. Many scientists consider memantine’s effect similar in scope to that of the cholinesterase inhibitors.
Adverse side effects of memantine include headache, constipation, confusion and dizziness.