Alzheimer disease

Information about Alzheimer disease

Alzheimer disease is a progressive degenerative brain condition that is the most common cause of dementia worldwide. Alzheimer disease affects at least 5 million persons in the United States, including approximately 1% of individuals in their 60’s and up to 8% of those above the age of 85 years. The usual presentation is insidious with impaired memory and cognition and change in personality. The course is generally progressive with eventual mental and physical disability and death due to complications of immobility.

Cause of Alzheimer disease

The cause of Alzheimer disease is not known, but it is characterized by marked atrophy of the cerebral cortex and loss of neurons. Histologically, Alzheimer disease is marked by senile plaques, spherical accumulations of β-amyloid, degenerating neuronal processes and neurofibrillary tangles. Functionally, there appears to be impairment of cholinergic transmission. The increasing prevalence of Alzheimer disease in the population due to increases in the elderly population has led to an increasing appreciation of the importance and the medical and social burden of Alzheimer disease. Early detection has led to attempts at therapy, the major goal being amelioration or slowing of its progressive course. Several medications have been found to alleviate some of the symptoms and signs of Alzheimer disease, but none have been proven to affect its ultimate course and outcome.

Treatment of of Alzheimer disease

The pharmacotherapy of Alzheimer disease has focused on increasing cholinergic function in the brain. Acetylcholine precursors, such as choline and lecithin, have not proven beneficial, but inhibition of acetylcholine metabolism using inhibitors of acetylcholinesterase has been found to be partially successful in improving symptoms of Alzheimer disease. Four acetylcholinesterase inhibitors have been approved for use for Alzheimer disease in the United States: tacrine (Cognex: 1993), donepezil (Aricept: 1996), galantamine (Razadyne: 2001), and rivastigmine (Exelon: 2002). An alternative approach to treatment of Alzheimer disease is inhibition of N-methyl-D-aspartate (NMDA) glutamate receptors which is thought to lead to less excitotoxic injury to the brain. A single NMDA receptor inhibitor has been approved for use in Alzheimer disease in the United States: memantine (Namenda: 2003).

Liver safety of Alzheimer disease

Therapy with tacrine has been associated with a very high rate of serum enzyme elevations, which can be dramatic although usually not associated with symptoms, jaundice or clinically apparent liver injury. Nevertheless, because of this side effect and the availability of other better tolerated cholinesterase inhibitors, tacrine is now no longer used. Except for tacrine, the drugs used for Alzheimer disease are rare causes of acute liver injury and have a low rate of associated serum enzyme elevations.

The agents used to treat Alzheimer disease include:

• Donepezil
• Galantamine
• Memantine
• Riluzole
• Rivastigmine
• Tacrine

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