Though the German neuropathologist Alois Alzheimer recognised what was to be known as Alzheimer’s disease as early as in 1906, the condition described by him was not considered common enough to warrant serious attention. However, by the 1960s - thanks to the use of antibiotics and vaccines - life expectancy had increased enough to throw up large numbers of cases of “senile dementia”. It took some time to realize that in most cases, senile dementia was nothing but Alzheimer’s disease.
Today, Alzheimer’s disease is recognised as a major illness, with an estimated 12 million sufferers worldwide. The disease is characterized by gradual loss of memory and decline in cognitive functions. Its incidence increases with advancing age, and a positive family history is a risk factor. Patients usually die of infections, with death occurring approximately 10 years after the onset of symptoms.
Histopathologically, beta-amyloid deposits, neuritic plaques, and neurofibrillary tangles are found in Alzheimer’s disease, and these are being targeted for future therapy. A major Alzheimer’s susceptibility gene, apolipoprotein E4 (ApoE4), may contribute to more than 60% of late-onset disease. Early-onset disease can be brought about by the APP (amyloid precursor protein) gene, and by presenilin-1 and presenilin-2. These are dominant genes, and inheritance from either parent could result in manifestions of the disease as early as in one’s 30s.
These and other insights were discussed at the recent World Alzheimer Congress 2000 in Washington, where it appeared that science is closing in on the disease. Clinical trials are targeting beta-amyloid, the peptide whose presence may be the earliest pathological development in Alzheimer’s disease. Immunization is being evaluated, and also inhibitors of secretases involved in processing of amyloid. Other approaches are also being pursued.
Since decreased amounts of acetylcholine are characteristic of Alzheimer’s disease, cholinesterase inhibitors e.g., donepezil, rivastigmine, tacrine, metrifonate and galantamine, could provide symptomatic treatment. These drugs improve cognition and behaviour but are not curative.
Higher levels of COX-2 (cyclooxygenase-2) in the brains of patients during the early stages of the disease suggest a possible role for non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment. Some believe that it is COX-2, and not beta amyloid, that produces the inflammatory manifestations of the disease. NSAIDs could therefore have a therapeutic role and could also help in prevention.
As an antioxidant, vitamin E may facilitate breakdown of free radicals contributing to brain damage in Alzheimer’s disease. Its role in Alzheimer’s disease is not established. An antioxidant that occurs naturally in the body is coenzyme Q10, or ubiquinone, but a synthetic version of this compound, idebenone, has not shown favorable results.
Ginkgo biloba is a plant extract with beneficial effects on brain and body cells and its use has helped some patients, but further study is necessary to determine its role in this condition. Huperzine A, a moss extract used in traditional Chinese medicine, acts as an acetylcholinesterase inhibitor and is a potential treatment for Alzheimer’s disease. Oestrogens, peripheral nerve stimulation and several other therapies have been tried out, but their roles are yet to be confirmed. Other drugs i.e., antidepressants, antipsychotics and anxiolytics, coupled with non-pharmacologic treatment, are employed to manage behavioural symptoms associated with Alzheimer’s disease, and to improve the quality of life.
What is exciting is the fact that many new leads are emerging in our understanding and treatment of Alzheimer’s disease. Perhaps a decade from now, old age need not be associated with senility any more.
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This article was published in Pharma Business 11th August 2000.
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