ALZHEIMER'S DISEASE: HOPE ON THE HORIZON?

ALZHEIMER'S DISEASE: HOPE ON THE HORIZON?



By Henrylito D. Tacio


They say memory is the first thing to go. More precisely, it's the first thing doctors consider in an evaluation. For 65-year-old Charito, memory impairment is indeed in the earliest stages. She has trouble with words and, sometimes, simple physical tasks such as preparing the table for dinner. Her memory troubles come and go. "There are times when I don't have any problem," she says. "But there are also instances that I don't know what I was doing at all."



Charito has been diagnosed with mild cognitive impairment and told she has an 80-percent chance of developing Alzheimer's disease. Her mother, at age 72, died of the disease. "Of course, I have fears that I may follow what my mother had gone through," she says. "I hope that that medical science can do something about this disease."



Actually, Alzheimer's disease has a gradual onset. Generally, it starts with subtle changes in memory function. "What comes first gets out last with the most recent memory getting lost first," explains Dr. Simeon Marasigan, associate professor at the department of neurology and psychiatry of the University of Santo Tomas.



In some instances, the patient may exhibit abnormal behavior. "People suffering from Alzheimer's may be unreasonable," explains Dr. Victor Chong, a neurologist with special interest in dementia from the University Malaya Medical Centre in Kuala Lumpur. "For example, a husband with Alzheimer disease may often accuse the wife of infidelity."



But as the disease progresses, language skills diminish, along with the ability to perform calculations or planning activities. A person who used to be very good at giving his opinions on certain topics, solving problems, and painting, may not be capable of doing them now.



Unlike in the past, doctors can now diagnose the disease with 90% accuracy, but proof can only be obtained by examining the brain of the patient after death. Unfortunately, many other disease processes can mimic Alzheimer's such as thyroid imbalances, vitamin B12 deficiency, brain injuries, tumors, and depression.



More than 26 million people now have the brain-wasting disease and this number will quadruple, to 106 million, by 2050. "By 2050, 1 in 85 persons worldwide will have Alzheimer's disease," said Dr. Ron Brookmeyer of Johns Hopkins University, who led the study on how many people have the disease.



The biggest jump is projected for densely populated Asia, home of almost half of today's Alzheimer's cases, 12.6 million. By 2050, Asia will have 62.8 million of the world's 106 million Alzheimer's patients. Currently, the Philippines has about 90,000 people having the disease.



For over 50 years, however, the symptoms of Alzheimer's were thought to be a normal part of aging, and a true disease only in people who had it before age 65. "However, here is an increase prevalence of Alzheimer's disease as one gets older," explains Dr. Marcos Ong, a neurologist and psychiatrist at the Brokenshire Hospital in Davao City.



"About 5 percent of men and 6 percent of women over 60 years of age are affected with Alzheimer's," says Dr. Wang Xiangdong, adviser of the mental health and control substance abuse program of the regional office of World Health Organization (WHO). "With the ageing of populations, this figure is projected to increase rapidly over the next 20 years."



Since the disease has been described by Dr Lois Alzheimer in 1907, it continues to baffle medical science. Until now, the cause of Alzheimer's disease remains a mystery. "Alzheimer's is one of the hottest areas of scientific research," declares Dr. Marasigan.



Science, however, has discovered that the gradual loss of brain function that characterizes Alzheimer's is due to two proteins, beta-amyloid and tau. "These two are the possible culprits," says Professor Edmund Chiu, a psychiatrist at St. George's Hospital in Melbourne University.



Beta-amyloid protein accumulates in the brains of patients with Alzheimer's disease, activating immune cells that try unsuccessfully to remove it. That triggers the release of poisons that ultimately kill nerve cells, leaving behind a trail of plaques and tangles – the remains of nerve cells and fibers, clogged up with beta-amyloid.



Many of the nerve cells that are destined to die show abnormal deposits of a protein called tau, which is assumed to be toxic to nerves. Tau formation is related to the severity of disease. "The more severe the disease, the more tau is found within the brain," informs Dr. Adrian Tan, a neurologist who works at the Paragon Medical Centre and the Mount Elizabeth Medical Centre in Singapore.



Alzheimer's has also been connected to a reduction of acetylcholine in the brain. Acetylcholine is a substance in the body that allows messages to travel from one nerve to another. For example, a person who decides to pick up a pen can act on the thought only when the hand receives the message from the brain. Studies have shown that Alzheimer's patients have a severe drop, sometimes 90 percent, of acetylcholine.



But despite all these discoveries, there is still no cure, or way to prevent the onset of the disease. Professor Simon Lovestone, chairman of the Alzheimer's Research Trust's scientific advisory board, is optimistic that the disease will soon be curable. "In our lifetime, some level of cure is possible," he said.



Dr. Patricio F. Reyes, a neurologist and neuropathologist who directs the Alzheimer's Disease and Cognitive Disorders of the Neuropathology Research Laboratory at Barrow Neurological Institute in Arizona, agrees. "I believe that if research continues its pace and focus we would have a major breakthrough within 5-10 years."



However, Dr. Reyes admitted that Alzheimer's disease is "multifactorial" hence its prevention and treatment will involve the combination of drugs which may include pills and/or a vaccine, changes in current lifestyle to reduce or prevent risks factors such high cholesterol, diabetes, head trauma and hypertension, and limit people's exposure to noxious agents in the environment.



Researchers around the world have found more than 30 different compounds that can retard, halt or prevent amyloid buildup in mice or else speed up its clearance. "Since most of these are still experimental and limited to animal studies, it is very difficult to predict results among human beings," says Dr Eleanor Ong, a neurologist at the Davao Doctor's Hospital.



In Canada, a University of Toronto team recently announced a promising new agent. A compound called cyclohexanehexol, or AZD-103, stopped beta amyloid accumulation in mice and reduced their symptoms. The compound is in Phase I of clinical trials.



Others are in Phase II. In Phase II a treatment's effectiveness is tested in groups of 100 to 300 people. Then, if it still holds promise, it will move to Phase III clinical trials on up to 3,000 patients with a control group. Neither patients nor clinical researchers will know who is getting the treatment until the end of the trial.



"It will take a couple of years for results," says Dr. Paul Fraser, professor of medical biophysics at the University of Toronto, "but these Phase III findings are going to come out one after another, and we will see what is best."



In the United States, Dr. Reyes reported that their institute has just finished working on the development of a skin patch for Alzheimer's disease which the US Food and Drug Authority has approved. "It is the only one available and it took us more than 4 years," he says. "It would avoid many the gastro-intestinal side-effects of medications such Exelon, an acetylcholinesterase inhibitor."



"The reality may seem bleak but there is hope," says Dr. Xiangdong. "Recent researches have been discovering new facets of the disease. Better understanding of risk factors may lead the way to postpone the onset and reduce incidence. And with the dedication of some scientists, physicians, and epidemiologists, we will witness more promising new therapies."



And as Dr. Manolete Renato Guerrero, chairman of the Department of Nuerosciences at the Davao Medical School Foundation, puts it: "There will come a time when Alzheimer's disease will become a thing of the past." -- ###