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Dementia: Alzheimer's disease

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VOL: 98, ISSUE: 45, PAGE NO: 32

Graham A. Jackson, MB, ChB, MRCPsych, MRCGP, is consultant old age psychiatrist, Leverndale Hospital, Glasgow

Dementia is a common condition and many health professionals will be involved in caring for those who have it. This series of four articles will discuss the different forms of dementia, its potential causes, common behaviour problems of those with dementia, assessment tests, and person-centred care.

Dementia is a common condition and many health professionals will be involved in caring for those who have it. This series of four articles will discuss the different forms of dementia, its potential causes, common behaviour problems of those with dementia, assessment tests, and person-centred care.

Common features and prevalence
Dementia is a syndrome, not a specific disease; that is, it is a set of symptoms. It is often considered to be an inevitable part of growing old, hence the use of terms such as 'going senile', or 'senile dementia'. This attitude is partly due to ageism, and partly to ignorance of its aetiology. Its most common features are summed up by the World Health Organization's definition (Box 1).

As the average age of a population increases, so the number of people with dementia rises. It is a condition that affects all socio-economic groups, but there is some evidence that prevalence varies, and that the main form of the syndrome is different in different countries. For example, in the United Kingdom and the USA, Alzheimer's disease is more common, while in Japan vascular dementia predominates (Tatemichi and Desmond, 1996). Different diagnostic criteria may account for some of this difference, but it is generally felt to be a true difference.

It is estimated that in the United Kingdom there are around 700,000 people with dementia (Alzheimer's Disease Society, 2001), a fact that has major health and social implications. McNamee et al (2001) have estimated that, for England and Wales, the total cost to social and medical agencies lies between £9.5bn and £13.5bn. These figures do not include the cost to carers in terms of time lost from work and from other activities.

The National Service Framework for Older People (DoH, 2001) sets out the agenda for improving older people's care in England and Wales. It is backed by substantial investment of £1.4bn extra per year by 2004 as a means of helping provide quality care, treating older people with dignity, and without age discrimination. The framework also calls for better integration of care services, and for person-centred care; that is, treating people as individuals and enabling them to make choices about their own care.

Although the features of dementia vary according to its particular type, it is, by definition, progressive, which means that the ability of the individual to lead a 'normal' life will eventually be seriously impaired. Memory impairment must be present to make a diagnosis, but this is not sufficient - there must be evidence of decline in other cognitive (thinking) skills, and there must be interference with the ability to carry out daily living skills. These changes must have occurred over at least a six-month period. Obviously, such changes do not occur overnight, therefore there is a period of time when, although there have been changes in the brain, they are insufficient to result in diagnosable disease.

Until fairly recently, people developing dementia did not come to the attention of medical services until there were behavioural changes, or marked impairment of their ability to look after themselves. However, the development and availability of new treatments have led to earlier involvement. One particular problem which remains, which is difficult for society to deal with, is that people with dementia often lose insight into their condition and will neither accept a need for help nor allow others to seek help on their behalf.

Effects of brain damage
The effects of the illness relate to which parts of the brain are affected. Most cognitive abilities depend upon normal functioning of more than one part; nevertheless, it is useful to think of which problems can result from damage to particular areas.

Frontal lobe damage
This part of the brain deals with what can be referred to as 'executive function', that is, the ability to plan and to make judgements. Damage to the frontal lobe, then, may result in personality change - often an early precursor of dementia. Normal frontal lobe functioning is also necessary for the production of, and understanding of, speech.

Frontal lobe damage may affect the emotions and motivation as well as the ability to communicate. There are different presentations to this, including disinhibition, apathy and lethargy, emotional lability and, sometimes, overactivity. In addition, some people might appear to be depressed. Alternatively, they might be totally unconcerned as to what is going on around them. Speech problems, too, are variable, but a common feature is a nominal dysphasia - the inability to find the correct word for something. Typically, the person can describe accurately what something is, saying, perhaps, of a clock 'it's to tell the time', but being unable to say the words 'clock' or 'watch' or even 'timepiece'. Where damage becomes more extensive, speech may develop into a 'jargon dysphasia', where nothing makes sense and a sentence is just a jumble of unconnected words or sounds.

Such communication problems are often associated with distressed or even aggressive behaviour. It is difficult to say whether this is because of disinhibition, or to frustration at being unable to be understood, or indeed both.

Temporal lobe damage
Damage here causes memory problems. Recent memory is affected most; for example, people remember the names of classmates from school 65 years ago, but not what they had for lunch an hour ago. Thus older memories are retained until a later stage - referred to as Ribot's Law.

It is likely that hallucinations and delusions are due to temporal lobe damage as they are not an uncommon feature of many forms of dementia.

Parietal lobe damage
Visiospatial skills, that is, the ability to orientate oneself, are affected by damage to this area of the brain, as is the ability to recognise people, objects or situations (agnosias). This can even result in an inability to recognise parts of one's own body.

Failure in orientation leads to various dyspraxias, such as being unable to put an arm in a sleeve, find the way to the toilet, or to lay a place-setting on a table.

Occipital lobe damage
Involvement of this part of the brain is less common in dementia, although it may sometimes be one of the focal signs of vascular dementia. There may be cortical blindness where, despite visual images going from the retina through the brain to the visual cortex (in the occipital lobe), the brain is unable to decipher the message. Although those so affected cannot see as such, at the same time they are aware of obstructions in front of them and can move around freely.

Common forms of dementia
Alzheimer's disease is the most common form of dementia and is discussed below. Other forms will be discussed in Part 2.

Alzheimer's disease
Alzheimer's disease accounts for about 50-60 per cent of cases of dementia in the UK (Lishman, 1998). The average age of onset is around 75, with the incidence increasing with advancing age, although some patients develop the condition in their 40s. There are suggestions that the incidence may decline in the very old, but this is not yet clear.

The onset of Alzheimer's is usually gradual, although often relatives pinpoint the onset of symptoms to a specific incident such as the death of a spouse, a spell in hospital, a move of house. Loss of memory is the most common presenting complaint, though often personality change precedes this. Deterioration tends to be a slow process, over many years, and clinical features relate to the involvement of mainly the parietal and temporal lobes, although any aspect of cognitive function can be impaired. Alois Alzheimer, a Bavarian psychiatrist, first described the disease in 1907 in a woman in her early fifties.

In a person with Alzheimer's there is usually generalised shrinkage (atrophy) of the brain. This is not invariably present, and some degree of atrophy occurs in older people. There is thus a large overlap in the degree of atrophy. In Alzheimer's, it is usually most prominent in the temporal lobes, the changes usually being bilateral and symmetrical.

At a microscopic level, the two distinctive features are the presence of neurofibrillary tangles in neurones, and plaques. Tangles are complexes consisting of, among other proteins, tau and ubiquitin. Tangles do occur in normal ageing, but are more numerous in Alzheimer's. Unlike plaques, however, the density of tangles does not relate to the degree of cognitive change. Plaques consist of various proteins around an amyloid (also a protein) core. Why these changes occur has not yet been established. It seems that there is a problem with the metabolism of amyloid and of tau, but how these processes interrelate, and whether they are the cause, or the result, of underlying disease, remains unclear.

The amyloid protein present in Alzheimer's arises from a precursor protein (APP). This has a role in the pathogenesis of the condition. Whatever the cause, the net result is cell death. The neurones which deteriorate are those which in general use the protein acetylcholine as a neurotransmitter. Hence in Alzheimer's there is a substantial reduction in the amount of acetylcholine in the brain. This is essential for the processing of information and for the transferring of messages from one part of the brain to another. Reduction of it, therefore, leads to impairment.

It is because Alzheimer's can affect so many different parts of the brain that so many aspects of cognitive function are impaired. Typically, there is loss of short-term memory; disorientation in time and space; loss of ability to carry out complex daily living skills such as dressing or making a cup of tea; speech problems; deterioration in personality, and various agnosias. Failure to recognise a spouse, or a house, can lead to particular difficulties in management, particularly as such a symptom can be so hard to understand.

Although the cause of Alzheimer's has yet to be established, various risk factors have been recognised. For example, it is known that there is a genetic component to the condition. This is more prominent in families with an early age of onset, but it can be present in some with later onset. The presence of Alzheimer's in a parent or sibling is associated with higher risk. In some early onset families, particular genes have been identified. The first of these was on chromosome 21. People with Down's syndrome have an extra chromosome 21, and are known to have a higher risk of developing Alzheimer's, and amyloid metabolism abnormalities have been associated with chromosome 21. There was early optimism, therefore, that the gene for Alzheimer's was on this chromosome. However, in other families, abnormalities have been found on other chromosomes, including 1, 5, 9, 10, 14 and 19 (Holmes, 2002).

Rarely, inheritance of Alzheimer's has been found to be autosomal dominant; that is, all those who inherit the gene from the affected parent (50 per cent of their children) will develop the disease.

Another protein that has a connection with Alzheimer's is apolipoprotein E (apoE). The gene for this substance lies on chromosome 19. ApoE has a role in the maintenance and repair of neurones. There are three forms: apoE 2, 3 and 4. It appears that inheriting the apoE 4 form from both parents increases the risk of Alzheimer's.

History of a previous head injury may increase the risk of developing Alzheimer's, although studies have been inconsistent. Other suggested environmental factors have included ingestion of aluminium (or other toxins), viral infections, deficiency of vitamins B12 or folic acid, and thyroid problems - however, the evidence for these as contributory factors remains rather weak.

Summary
Dementia is a syndrome resulting from disease of the brain, not a specific disease; the form the dementia takes depends on the area of the brain that is affected. The increasing number of people with dementia in the United Kingdom has major health and social implications. Health professionals from many disciplines will therefore need to have an understanding of the nature of the condition so as to be able to give appropriate care. The most common form of dementia is Alzheimer's disease.

Next week: Further forms of dementia

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