Alzheimer's Disease is a distressing condition, for the sufferer and for all those who care about the victim. Incidence of the disease is sharply increasing - and there is no cure. But great progress is being made in understanding the condition's basic biochemistry.
Much of this work was carried out at the National Institute on Ageing in America under the direction of Zaven Khachaturian. It is hoped effective treatments will be available soon, followed closely by a cure.
At least 16 million people worldwide suffer from Alzheimer's. Ireland has recorded 33,000 cases. Most cases develop after the age of 65 in people with no family history of the disease, although genetic factors predispose people to the disorder. It is the leading cause of dementia in the elderly. A small number of cases (2 to 7 per cent) are an early onset variety and can afflict people as young as 30. Early onset Alzheimer's is an inherited condition, distinct from late onset.
The disease silently destroys the brain. The first symptom usually is forgetfulness, followed by severe memory loss, confusion, unco-ordinated movement, garbled speech, personality changes, hallucinations and mood swings. As the brain deteriorates, the rest of the body gradually closes down and, invariably, the victims are left incapable of caring for themselves. Death ensues two to 20 years after the appearance of the first symptoms.
Alzheimer's has existed since ancient times and writers have often described the typical symptoms. Shakespeare's King Lear is a well-known example, where Lear is losing memory and becoming disoriented. It was defined as a distinct disease in 1906 by a German physician, Alois Alzheimer.
He described a patient who presented with volatile behaviour, memory loss, disorientation, hallucinations and paranoia. After the patient's death, Alzheimer examined her brain and described the odd growths - tangles and plaques - now considered the disease's unambiguous fingerprint. A protein called beta-amyloid forms sticky clumps at the core of the plaques in the brain affected by the disease.
The sector of the population at greatest risk are people aged 85 and over - the fastest-growing population sector in developed countries. People are also, on average, physically healthier at all ages than in the past. Therefore, not only are absolute numbers of victims on the increase, but also the disease's average duration is increasing. Health care is expensive and unless effective treatment or a cure is forthcoming society will soon face an enormous financial burden.
The brain is a complex arrangement of interconnected nerve cells: the neurons. In the absence of disease the brain will continue to function well into the tenth decade of life. In Alzheimer's, neurons gradually lose the ability to extract energy from glucose (the brain's principal food) to carry out essential repairs, and eventually to connect to other neurons. Neurons often die. It is not known what causes the brain systems to deteriorate with the disease.
The first breakthrough in understanding the condition's biochemistry was made in 1976 when an enzyme necessary to make acetylcholine was found to be deficient in affected brains. Acetylcholine is a chemical necessary in the transmission of electrical signals between neurons. Research has shown acetylcholinecontaining neurons play an important role in memory.
Later work in the 1980s and 1990s has identified genes responsible for early-onset Alzheimer's and genes that predispose people to develop the much commoner late-onset. Identification of genes opens the possibility of genetic testing. But a positive test for the late-onset predisposing gene does not necessarily mean a person will get Alzheimer's. One must also question, on ethical grounds, the value of a genetic test in a situation where there is no cure for the disease.
Alzheimer's is a complex disorder and it is likely that genetic and environmental factors interact to initiate the process. Some years ago there was a feeling that ingestion of aluminium played a significant role.
This hypothesis no longer finds favour with most researchers in the field. The three systems - neuronal intercommunication, energy metabolism of glucose and neuronal repair - work synchronously to keep the brain healthy. It is probable that a disruption of any of these systems, whether from imbalanced nutrition, toxins, trauma or infection could initiate degenerative changes culminating in Alzheimer's.
To my knowledge only two drugs are on the market to treat Alzheimer's: Tacrine and Donepezil Hydrochloride. Both act to slow down the breakdown of acetylcholine and thereby to help communication between damaged neurons. The drugs can slow the rate of deterioration in some patients but cannot prevent the illness's final victory. Recent research findings on the protein that accumulates to form the characteristic plaques and tangles holds the promise of the development of a more effective drug to treat the disease.
If you are in your 60s and notice your memory is not what it used to be, should you worry that Alzheimer's may be developing? No. Memory performance in everybody slowly declines from the age of 20. The decline becomes more noticeable beyond the age of 60 but there is considerable normal variation. With any luck at all your mind will remain clear to the end.
William Reville is a senior lecturer in biochemistry at UCC