Better understanding of dementia leading to more effective therapies

Conditions Expert Dr. Otis Brawley Chief Medical Officer,
American Cancer Society

Understanding dementia

Just a decade ago when a diagnosis of dementia was given, very little could be done for most patients except for treating behavioral disturbances and changing the environment to support safety and functioning.

Better understanding of the biology of these illnesses has led to some treatments that can improve cognition. For most, the current treatments are far from satisfying, but they do give us hope that better drugs can be developed.

The dementia should evaluated and diagnosed by a physician with special training in cognitive disorders. This may be a neurologist, a psychiatrist or, in certain instances, an internist or geriatric physician with specialized training. A precise diagnosis is important for effective management.

There are several types of dementia other than Alzheimer's disease. Drugs used in the treatment of one type of dementia can actually worsen other forms of dementia. Haloperidol (Haldol) is indicated in the treatment of behavior issues in a patient with Alzheimer's disease, but can be harmful to a patient with dementia caused by Parkinson's disease.

Acetylcholine is a neurotransmitter in the brain, meaning it is a chemical used to send messages from nerve to nerve. Researchers have found that patients with Alzheimer's disease and several other types of dementia have lower levels of this acetylcholine.

Drugs that stop the action of cholinesterase, the enzyme that breaks down acetylcholine, are useful in the treatment of Alzheimer's disease. These "cholinesterase inhibitors" include tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne, formerly called Reminyl).

They are approved by the U.S. Food and Drug Administration for use in several types of dementia and widely available internationally. These drugs come in pill and liquid form. Some are even available as a skin patch for transdermal application.

A cholinesterase inhibitor should usually be started in early dementia and, if possible, be continued throughout the disease.

In clinical study, they appear to slow the progression of the dementia in some patients. These drugs have significant side effects, such as slowing of the heart, gastric upset, nausea and vomiting, as well as difficulty urinating.

Memantine (Namenda) is another oral medication. It is widely available for patients with moderate to severe Alzheimer's. It blocks stimulation of a specific receptor in the brain, an NMDA receptor. When stimulated, these receptors cause a cascade of events that lead to dementia. Memantine is also especially useful in the treatment of patients with Alzheimer's disease and patients with vascular dementia. Vascular dementia is a disease caused by decreased blood flow and oxygenation to parts of the brain.

In a 28-week study of Alzheimer's patients, 250 were in a randomized trial to memantine or placebo. Compared with the group taking placebo, memantine-treated patients had less deterioration in mental function over the 28 weeks. This drug appears to provide a small but significant benefit in terms of cognition. Unfortunately there was no effect on behavior or ability to perform activities of daily living. Scientific study has proved this drug generally useful for six months, but the long-term benefit is unknown.

Memantine has fewer side effects than the cholinesterase inhibitors. Dizziness is the most common side effect associated with memantine. A very small number of patients have auditory and visual hallucinations because of the drug. It also may to increase agitation and delusional behaviors in a small number of patients.

Memantine should be started in patients with moderate to severe Alzheimer's. It is often used in combination with a cholinesterase inhibitor. Since it may be disease-modifying, many physicians suggest it be continued even when there is no clinical improvement.

Much attention has been given to Alzheimer's disease. Less is known about the treatment of other common dementias.

In general, cholinesterase inhibitors have shown some benefit for patients with vascular dementia, those with mixed Alzheimer's and vascular dementia, patients with the disease known as "dementia with Lewy bodies," and dementia from Parkinson's disease. These drugs are useful in certain variants of frontotemporal dementia. Cholinesterase inhibitors are not useful in dementia caused by Huntington's disease or traumatic brain injury. While cholinesterase inhibitors are useful in many early dementias, studies have not shown that treatment of patients with mild cognitive impairment, which is the condition before dementia, prevents or slows progression to dementia.

Studies of treatment with estrogen, ginkgo biloba, vitamin E and vitamin B supplementation have been done. These drugs do not appear helpful. Some antidepressants have been shown to be effective in treating mood disorders associated with dementia, but they do not improve cognitive function.

Several studies have demonstrated that dementia patients given structured exercise programs and occupational therapy have a less severe decline in activities of daily living and improved quality of life. These benefits have been observed over periods of years.