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Published by: Nick Bantolo on Jun 29, 2010
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What research has taught us about Alzheimer’s and Dementia Diseases
 A.F. Jorm, Ph.D. National Health & Medical Research Council Social Psychiatry ResearchUnit Australian National University 
Five years ago I was in the situation that many of you are in today living with a dementingrelative, but having all too little knowledge of the condition he was suffering from. Since then,my dementing relative has died and I have become a professional researcher on the topic of dementia. I wish that 5 years ago I knew as much about dementia as I do now. My aim todayis to provide answers to some of the questions you may have as care-givers. I will pose thesequestions one by one and try to give an answer in the light of current research knowledge.
What is Alzheimer's Disease?
Alzheimer's Disease is a disorder affecting the brain which causes severe deterioration inmemory and self-care skills and which can cause distressing changes in personality. In theearly stages of the disorder the changes may be subtle. Often the first changes are in thearea of memory, with particular difficulty in remembering new things. In some cases,personality changes are the first problem noticed. Sufferers may be suspicious, irritable,changeable in mood, stubborn, impatient or easily upset. In the early stage, care-givers willnot be aware that brain changes are occurring to produce these effects and the dementingperson may be seen as deliberately willful or difficult. As the disorder progresses, all aspectsof intelligence are affected and the former personality is lost. Eventually, the sufferer may bebedridden, incontinent, and unable to communicate in any meaningful way. Death usuallyoccurs sometime after through some other medical condition such as an infection, but theunderlying cause of death is Alzheimer'sDisease.Alzheimer's Disease has been known about since early this century, but until a few years agoit was seldom heard about. The reason for this change in awareness is curious. WhenAlzheimer's Disease was first described by the German physician Alois Alzheimer in 1907, itwas in a 51 year old woman. Other early cases were also described in people under the ageof 65. It therefore came to be believed that Alzheimer's Disease occurred only in peopleunder the age of 65 and, because Alzheimer's Disease is rare in middle-aged people, it wasbelieved to be a quite rare neurological disorder. At this time, Alzheimer's Disease wasdistinguished from the common "senile dementia" which affected elderly people. Manyphysicians believed (and some still do!) that senile dementia is caused by blocked arteries,with the brain's blood supply becoming slowly strangled.This distinction between Alzheimer's Disease (occurring under age 65) and senile dementia(occurring over age 65) persisted until fairly recent times. It was only in the late 1960s andearly 1970s that researchers studying the brains of people dying from senile dementia foundthat most of them had the brain changes of Alzheimer's Disease. It then became common tosay that these people suffered from "senile dementia of the Alzheimer type". More recently,the term "Alzheimer Disease" has been extended to cover elderly cases as well as themiddle-aged ones. Research on the subject has thus led to a revolution in thinking, whereAlzheimer's Disease has been transformed from a rare neurological disorder affecting the
middle-aged to one of the most common disorders of aging. This broadening of the conceptof Alzheimer's Disease may now be going too far. In the U.S. it has become fashionable torefer to all elderly dementing people as Alzheimer's sufferers. Although Alzheimer's Diseaseis the major cause of dementia in the elderly, it is not the only cause, so where the diagnosisis uncertain we should refer to them simply as "demented" or "dementing".
What Happens to the Brain in Alzheimer's Disease?
Several different brain changes occur in Alzheimer's disease. Two of the principal changeswere first described by Alois Alzheimer, after whom the disorder is named. These changesare the "senile plaques" and "neurofibrillary tangles".
Plaques and Tangles
Plaques and tangles can be observed in the brain of an Alzheimer's sufferer under amicroscope at autopsy. Senile plaques occur outside the nerve cells of the brain. In a senileplaque the nerve cells in a small region of the brain begin to degenerate and a substancecalled "amyloid" accumulates in the center of this region of degeneration. Amyloid is a proteinthat has no normal role in the body and no one knows for sure why it forms. Senile plaquesalso contain quite a lot of aluminum and silicon, which some researchers think is an importantclue to the causes of the disease. I will say more about this later.Neurofibrillary tangles occur inside the nerve cells of the brain. They are tangles of fiberswhich probably disrupt the normal functioning of the nerve cell. Again, nobody is sure whythey form.Plaques and tangles occur in normal aging as well as in Alzheimer's Disease. Most elderlypeople will have some plaques and tangles in their brain. However, in Alzheimer's Diseasethese changes become much more frequent. The severity of the mental changes inAlzheimer's Disease is closely related to the number of plaques and tangles in the sufferer'sbrain.Although one might expect that plaques and tangles occur evenly throughout the brain inAlzheimer's Disease, this is not the case. Certain areas are greatly affected and otherslargely spared. In the early stage of the disorder, the areas of the brain controlling learningand memory are most affected, explaining the difficulty in acquiring new information, which isso characteristic of Alzheimer's Disease. Later, areas associated with language, orientation inspace and forward planning become affected. Least affected are the areas of the brainconcerned with sensation and movement.
Chemical Messengers
In the last 15 years, other important brain changes have been discovered. These involve"neurotransmitters" which are chemicals used by the brain to send messages from one nervecell to another. There are many different types of chemical messengers in the brain and eachnerve cell has one of these types for its communication with other nerve cells. One of thesechemical messengers is acetylcholine and it has been found to be severely lacking in thebrains of Alzheimer's Disease sufferers. The nerve cells which are well known, it isimpossible at present to observe these while a person is still alive. It is only after death, atautopsy, that plaques and tangles can be studied. For this reason, a postmortem diagnosis isnecessary if you want to know for sure whether or not your relative is suffering fromAlzheimer's Disease.
What Causes Alzheimer's Disease?
We do not know what causes Alzheimer's Disease, but there are three plausible theories: thegenetic theory, the toxic exposure theory, and the infectious agent theory.
1. Genetic Theory
Genetic factors seem to be quite important in Alzheimer's Disease, particularly for early-onsetcases. A genetic theory of Alzheimer's Disease accounts for the observations that suffererstend to have a family history of Alzheimer's Disease, or a family history of Down's syndrome,and an excess of the lunar loop fingerprint pattern. However, genetic factors cannot be thewhole story, as can be seen from studies of identical twins. Identical twins are geneticallyidentical, so if genetic factors were the whole cause of Alzheimer's Disease, both twinsshould either be affected or both unaffected by Alzheimer's. However, many cases have beenfound where one elderly twin is affected and the other is not. Such cases show thatenvironmental factors must play some role. We are currently investigating a number of suchtwins in Australia to help discover what these environmental factors might be.The genetic theory has recently received a considerable boost by the discovery that there is agene on chromosome 21 which produces the A4 (or beta) protein found in the core of senileplaques.This gene probably has some useful function in the body, but in old age it tends to go wrongand result in senile plaques. This is almost certainly not the gene which causes Alzheimer'sDisease. There are likely to be other genes involved which could, for example, have an effecton this particular gene and there may also be toxic chemicals which could affect the gene. Inother words, the discovery of this gene is but a link in the chain and not the ultimate cause.Nevertheless, it is a tremendous breakthrough, and it is noteworthy that Australianresearchers were at the forefront of this work.The middle-aged occurrence of Alzheimer changes in the brain in Down's syndrome hasbeen explained in terms of their having an extra copy of this gene. The extra gene leads thebody to produce the abnormal protein in larger quantities. Some researchers have recentlysuggested that a similar mechanism might be responsible for Alzheimer's disease in normalpeople. Rather than have a complete extra copy of chromosome 21 (as in Down's),Alzheimer's sufferers may have an extra copy of a small part of this chromosome. This theoryis controversial, however, and we need to wait till the research is confirmed by others.
2. Toxic Exposure Theory
It is quite possible that a toxic chemical could play a role in producing some cases of Alzheimer's disease. The disorder could be produced by killing off the nerve cells in certainsmall regions of the brain which use the chemical messenger acetylcholine. If these nervecells were destroyed, the effects would spread to other areas of the brain important tomemory and problem solving.The possibility that a toxic chemical could produce such an effect has become more plausiblefollowing recent research on Parkinson's disease. In this research some young people werefound to develop Parkinson's disease and it was discovered that they had all used a syntheticheroin which was contaminated by the chemical MPTP. The chemical was found toselectively destroy nerve cells in quite a small area of the brain involving the chemical

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