4
Forgetfulness or Dementia?:
where is the line between the two, and what can you do about it?
At some point, you notice that your grandmother’s remarks are becoming very repetitive. And when you mention your sister’s new partner, she doesn’t know who you mean, though you told her the whole story half an hour ago. This will be a familiar picture to most people with an ageing relative. You think to yourself: Are these the first signs of dementia?
Many people, especially once they have turned 60, wonder where the line between forgetfulness and early dementia lies. You forget — for the second time in a few days — where you left the car keys, and have to spend five minutes searching for them. Barbara Strauch, science editor of The New York Times, describes in The Secret Life of the Grown-Up Brain that she often goes down to the basement of her house to get something, but once she’s there she no longer knows what she came for.[1] She looks around her for a while, panicking at the thought that her memory is beginning to fail her. Yet she’s only 56. She decides not to give in to this forgetfulness and racks her brains to remember why she came down. Unsuccessfully. It’s only once she gets back to the kitchen and sees the empty paper-towel holder that the penny drops. Strauch attributes her memory blackout to her age. But she realises that the problem affects a lot of people and needn’t be a sign of pathological decline.
From my own experience, I know that this kind of memory failure can happen regularly from your thirties onwards. I’m not worried about it — yet! The reason is probably that I try to do too many things at once. Research shows that people in their thirties are likely to put these lapses down to their busy lives, while people in their fifties blame them on old age. But the memories of people in the latter age group are mostly in good shape, even if they themselves are not so sure of that.
Nevertheless, a day may come when you or others notice that your mental faculties (memory, concentration, thinking skills) are declining faster than average. Doctors and psychologists call this mild cognitive impairment (or MCI), and there has been an enormous upsurge in research into this issue over the last decade. How do you diagnose MCI? Exactly when should you start to worry about it? Are there demonstrable changes in the brain that herald the onset of dementia? What kinds of dementia are there, and how do they affect the brain?
A DIAGNOSIS OF MCI
Gerard is very concerned about his wife, Esther. She is only 58, but her memory seems to have become much worse over the last few months. She regularly repeats things she said earlier in the day. She forgets routine chores, such as ringing the dentist, or doing the shopping. Esther herself feels she can’t trust her memory anymore. Though she’s always had a good sense of direction, she’s recently got lost in town on more than one occasion. Sometimes she seems confused, and she sleeps badly — even if she takes a sleeping pill, she never gets more than a few hours’ sleep. Her GP refers her to a geriatrician. A brain scan reveals no abnormalities. Further tests show that Esther still knows the names of friends and acquaintances, though if she hasn’t seen someone for a few weeks she might have difficulty recalling his or her name. She knows what the date is and where she is. And although it requires more effort, she can still do her job. Gerard tells the geriatrician that she has changed in the last six months: from time to time, she appears to have difficulty in following conversations and functioning normally. He’s afraid that she is in the first stages of dementia and wonders if there is any medication that could halt the process. The diagnosis is MCI, which can herald the onset of Alzheimer’s, though not in everyone. The geriatrician gives Esther and Gerard advice, but also makes it clear that there is no medication that can help.
If you want to find out whether you have signs of MCI, take a look at the following checklist.
You don’t have to be suffering from all these symptoms. What matters is that cognitive problems are clearly present and have increased in recent months. You’re still able to function at home and at work, but people close to you have noticed that you’re having memory problems or that you’re no longer able to keep a grip on everything. Of course, even if you recognise a number of these signs, that doesn’t necessarily mean that you have MCI. That diagnosis can only be made by an expert (a geriatrician, neurologist, or neuropsychologist). But it is advisable to talk to your GP about it, to see whether a referral for further examination is appropriate.
How do people with MCI score on tests that measure cognitive skills? These neuropsychological tests are not always used in diagnosing MCI, though it would be good if they were because they reveal whether those skills are still intact. Specialised memory clinics do use such tests. An exhaustive session charts the various skills: memory, concentration (which neuropsychologists call attention), observation, speed of processing, and the executive functions (the ability to plan and keep an overview, abstract thought, cognitive flexibility, and the capacity to simultaneously process different items of information). You might expect that, on these tests, the performance of people suffering from MCI would lie exactly between that of healthy peers and of dementia patients. Research comparing different groups of people with and without MCI has indeed confirmed this. Yet it is possible for someone with MCI to score normally — or, rather, still score normally — in memory tests. These are people whose memory was previously better than most, so even if their memory decline is above average, they can still perform within the normal range. Take Peter, for example, who at the age of 40 took a 15-word memory test. After 15 minutes, he could still remember 13 of the items read out to him. That is a very good score. However, the test result was not recorded, and Peter himself no longer knows what his score was. At the age of 65, he starts to experience memory problems, which are confirmed by his wife. He does the 15-word test again and can recall seven items after 15 minutes. That is an average score. But his memory has nevertheless declined more than average: while his peers can recall three words fewer than when they were 40, he recalls six words fewer. Unfortunately, most people have no earlier tests for comparison when they first present with memory issues at the GP or clinic. That is why subjective memory problems play an important role in the diagnosis of MCI, particularly if they are confirmed by someone who knows the patient well.
Memory problems are the most prominent symptom of MCI. It’s important to keep track of them, since any further deterioration may be a sign of developing dementia. In a test requiring the subject to commit a short story to memory, people in the early stages of dementia almost immediately start to make mistakes in recalling the information. Research has shown that this is mainly the consequence of a lack of concentration while listening to the story. As a result, the information is not properly stored. But memory problems are not the only symptom of MCI. Sufferers’ cognitive flexibility is affected, as demonstrated in tests involving the switching of letters and numbers (1 for A, 2 for B, and so on). Compared with healthy peers, people with MCI do less well on this measure.
And what about speed of information processing? As we saw earlier, this is one of the skills that declines the fastest as we age. And indeed it deteriorates faster in many MCI sufferers than in healthy older people. An Australian study showed that poorer performance on the digit symbol substitution test (see figure 6), a common measurement of speed of information processing, was a predictor of the development of MCI four years later. In this study, over 2000 subjects between the ages of 60 and 64 were followed for four years. Of this group, 64 people showed clear signs of cognitive decline. The results of a memory test using words and another test measuring processing speed had some predictive value: a lower score at first measurement was often associated with decline later on.
CHANGES IN THE BRAIN ASSOCIATED WITH MCI
Though memory functions are not located in one specific part of the brain, there are certain areas that are of special importance. The most important is the hippocampus (figure 13) and the surrounding cerebral cortex in the temporal lobe. The hippocampus is a crucial part of the neural network (including the prefrontal cortex) involved in memory. It is not surprising that researchers investigating MCI looked at the structure and activities of this organ. An obvious question in MCI is this: is the hippocampus damaged and its function compromised?
The hippocampus consists of millions of brain cells. MRI scans measuring the quantity of grey matter can tell us if there is a link between reduced volume and the development of Alzheimer’s. A recent study combined the results of six longitudinal studies tracking reductions in the size of the hippocampus over a number of years in people with MCI, some of whom developed Alzheimer’s and some of whom didn’t. The researchers also looked at other brain structures, but the hippocampus and the surrounding cerebral cortex were the only structures that displayed a reliable association with MCI and, later, Alzheimer’s. In other words, on the basis of MRI scans it could be said, retrospectively, that a decline in grey matter in the hippocampus correlated with the development of Alzheimer’s a number of years later.
The Institute of Psychiatry in London conducted a study of 103 people with MCI that looked at changes in the shape of the hippocampus rather than in its volume. The changes in brain tissue associated with Alzheimer’s result in an alteration in the shape of the hippocampus, as measured by a computer program. In 80 per cent of cases, an abnormally shaped hippocampus was accompanied by the development of Alzheimer’s one year later.
In addition to grey and white matter, there are other major types of matter in the brain that play a key role in metabolism and the transfer of stimuli. A special MRI technique known as magnetic resonance spectroscopy (MRS) allows scientists to measure the concentration of such matter. Together with a colleague, I compared all the studies into the differences between older people with MCI and their healthy peers that were performed using MRS. We found that in the hippocampus in particular, the reduction in matter involved substances important for an efficient metabolism.[2] As had been shown earlier, this reduction is much more marked in people with Alzheimer’s.
Other studies have revealed that the production of acetylcholine, an important neurotransmitter, declines as we age. Acetylcholine plays a role in learning and memory, but also in activating muscles. In Alzheimer’s, the neurons that make acetylcholine are damaged and the levels of the transmitter seriously affected. Medications to combat Alzheimer’s therefore aim to activate or mimic the effects of acetylcholine.
Another important change in older brains is the formation of ‘tangles’ or ‘plaques’ in brain tissue. As the name implies, tangles are twisted, non-functioning transport proteins (which look like threads and are found in neurons), while plaques consist of insoluble deposits of protein fragments. In Alzheimer’s, these proteins are abnormal and damage cerebral function. How this comes about is uncertain, though we know that genetics plays a role.[3]
Figure 15 illustrates the extent to which plaques, tangles, and neuron loss occur in normal ageing, in MCI (as a precursor of Alzheimer’s), and in Alzheimer’s itself. The illustration at top right shows what the brain of an 80-year-old looks like if that person has few cognitive problems, while the one below on the left belongs to a person suffering from memory problems but not from dementia. The image below on the right shows the brain of a person whose memory problems are so severe that a diagnosis of dementia is appropriate.
FIGURE 15. Tangles and plaques are absent in the brains of young adults (top left); increase slightly in normal ageing (top right); increase further in people with MCI (sometimes a precursor of Alzheimer’s), primarily in the temporal lobe (bottom left); and are everywhere in the brains of people suffering from Alzheimer’s (bottom right). The darker the colour, the greater the number of tangles and plaques.
Two things are noteworthy here. First, the more severe the decline in cognitive function, the greater the number of plaques, tangles, and areas with fewer neurons. And second, their location is different: in a person with MCI, the hippocampus is most affected; while in someone with Alzheimer’s, a much wider area is involved. Finally, in Alzheimer’s there is often inflammation of the brain tissue, which doesn’t occur in normal ageing.
An obvious assumption would be that the presence of protein plaques indicates declining cognitive performance. In other words, the more plaques there are, the greater the deterioration in memory and concentration. However, an important question is whether this applies only to dementia sufferers, or if it is also true of people with milder forms of protein build-up, as seen in some otherwise healthy seniors. A problem up to the very recent past was that this kind of protein deposit could only be established through a post-mortem examination. It could not be tracked as people aged. Luckily, a special brain-scanning technique has now been developed to measure protein accumulation.[4] Researchers at the National Institute of Aging in the US used this technique to study 57 healthy people aged around 80. The results of cognitive skills tests from 11 years earlier were available. The scans showed that the older people were, the more protein build-up there was. And the amount deposited was related to the degree of cognitive decline in the 11 years preceding the scan. This study demonstrated that it is not only the accumulation of large amounts of protein characteristic of Alzheimer’s that is associated with mental decline. It seems likely that milder forms of protein build-up also have an effect. These milder forms appear in many healthy seniors, and are probably responsible for the less serious decline in skills that is common to the majority of the ageing population.
In the next few years, neuroscientists will attempt to refine even further the analysis of brain scans. The question is whether it’s possible to scan the brains of people complaining of cognitive problems to see who is at risk of developing dementia and who isn’t. If that were the case, targeted action in the fields of nutrition, exercise, and medication could be taken to prevent people in the high-risk group from developing dementia.
Researchers at the University of Newcastle in Australia recently made the first attempt to find out if it’s possible to use scans and other information to determine who is at greater risk of developing Alzheimer’s. They combined various test results and used special computer software to see which mix of factors had the greatest predictive power (that is, predicting who would develop Alzheimer’s within two years). The researchers examined three factors: the volume of various brain structures as measured by MRI scans, the presence of proteins in the cerebrospinal fluid (obtained through a lumbar puncture) that have been linked to Alzheimer’s,[5] and neuropsychological tests (in memory, attention, and executive functions). Values were obtained for each of the three factors from a dozen brain structures (through MRI scans) and a dozen neuropsychological tests. On their own, the tests proved to have the greatest predictive value. But a combination of measurements from each of the three factors predicted the onset of Alzheimer’s even better. This included memory tests, the volume of the hippocampus and the surrounding cerebral cortex, and the ratios between certain proteins in the cerebrospinal fluid. The combination provided a correct prediction in 67 per cent of cases.[6] That percentage is not high enough, since in many cases the prediction would be wrong, but it is a step in the right direction. Adding lifestyle factors (diet, exercise, mental activity) to the mix would undoubtedly make the model more successful.
We saw earlier that a reduction in the grey matter in the hippocampus is not a good sign. But what about the activity of this organ? Researchers at the University of Berlin scanned the brains of two groups of subjects while they were performing a memory test. The first group had no memory problems; the second reported subjective problems (that is, they themselves thought that their memories were deteriorating, but no objective neuropsychological tests had been performed). The scans showed that the hippocampus was less active in the second group — apparently the hippocampus, the ‘memory centre’ of the brain, was beginning to slow down. At the same time, the people with memory problems showed more activity in the front part of the brain, particularly on the right side. Despite these differences, the two groups performed equally well on the memory test — there was no decline in actual performance. This confirms the idea that people whose cognitive skills are beginning to decline have a less efficient hippocampus and compensate by using the frontal cortex more.
Another study of brain activity in people with MCI looked at a state in which the brain is ‘free’, rather than at memory processes. Researchers at the VU Medical Centre in Amsterdam examined patterns of brain activity in people who were lying awake but inactive in the scanner. This is termed ‘a resting state’. Of course, even then the brain is busy. Subjects might think about what they did today, or what they’re going to do later, or something else. The researchers compared scans of Alzheimer’s patients, people with MCI, and healthy volunteers. Then they followed the subjects for three years to see whether the difference in activity predicted the onset of Alzheimer’s in the MCI group. Of the 23 participants in that group, seven developed Alzheimer’s in the subsequent three years, and 14 remained mentally stable. Of the remaining two, one developed another form of dementia, and the other dropped out of the study. The researchers discovered that the brain scans of those who developed Alzheimer’s, made three years earlier when they were outwardly indistinguishable from the other members of the MCI group, showed that two areas in the posterior part of the brain that are important for autobiographic memory and self-awareness worked together less well than in those who did not develop Alzheimer’s. Co-operation between different parts of the brain can be measured by checking if they are active in the same way, to the same degree, at the same time. You could compare it to two people dancing together — a folk dance, for instance, where you hold each other’s hand. If both co-operate, they move simultaneously. If one of the partners does not co-operate, the pattern is disrupted and there is no harmonious movement. The study revealed that reduced communication between these two areas of the brain was linked to the seriousness of cognitive decline. These findings will probably be used by memory clinics in the future. More specifically, if an increasing reduction in connectivity is demonstrated through, say, six-monthly testing, this could make an important contribution to the early diagnosis of Alzheimer’s. In the future, information from such scans could very well be used to diagnose the earliest stages of the disease.
FROM MCI TO ALZHEIMER’S
In May 2011, a controversy raged in the pages of The New York Times about the seriousness of MCI. The newspaper was flooded with letters following the publication of an article by American academic Dr Margaret Gullette, in which she argued that many people with MCI managed to cope with their declining cognitive skills. Such people often have a positive outlook, she claimed, and get a lot of support from friends and family. The general tenor of the article was that cognitive impairment is mostly not such a serious matter — a slight decline in memory and thinking skills is a normal part of ageing, and our culture should be less obsessed with perfect mental functioning. A positive outlook keeps you active and prevents further decline. The letters came from indignant relatives of Alzheimer’s patients and people suffering from advanced MCI. Having witnessed up close a loved one’s unequal struggle with the destructive effects of the disease, they objected in the strongest terms to the view that a positive outlook and support from family are enough to be able to live with cognitive impairment. Neurologists, too, became involved in the debate. They were concerned by Gullette’s views because they seemed to trivialise the gravity of the daily problems faced by MCI patients.
The angry relatives were right to say that a positive outlook and lots of help and support, however good, cannot prevent Alzheimer’s. Quite apart from that, it is possible that Margaret Gullette and the letter writers were talking about different groups of patients. Various studies have shown that nearly half of the people diagnosed with MCI do not go on to develop Alzheimer’s in the following five years. One in seven improves to such an extent that the diagnosis of MCI no longer applies. Gullette was probably thinking of this group, while the letter writers were referring to the other. No one raised this distinction between those who do and those who don’t go on to develop dementia in the years following the diagnosis. Nor can this distinction be made when MCI is diagnosed. That is why more research is needed that focuses on exposing the factors that lead to dementia.
Why one person develops dementia and another doesn’t has probably to do with a number of factors that reinforce one another. Genetics play a role, as do lifestyle factors (little or no exercise, little mental and social activity, unhealthy diet). MCI that does not progress, where the patient does not develop dementia, is mostly caused by psychological factors such as long-term depression, stress, or burnout. A temporary reduction in brain function caused by vitamin deficiency, low thyroid function, or the side effects of medication can also lead to MCI.
Is everyone at risk of Alzheimer’s? Probably not, as we saw with Hendrikje van Andel, whose brain showed no traces of the disease at the age of 115. At the present time, too little is known about the decisive factors in the development of Alzheimer’s in people with MCI. Worldwide, a considerable amount of research is devoted to this issue, and it is perfectly possible that in a few years’ time we will know much more. Because the disease begins gradually and progresses slowly, it is always preceded by mild cognitive impairment with no disastrous consequences. This means that the first stage is not always recognised as MCI. And there is still no effective treatment. Nevertheless, we do have some idea about steps we can take to exert a favourable influence on the outcome.
WHAT CAN YOU DO ABOUT MCI?
Can we halt the mental decline that accompanies MCI? There is little hard scientific evidence to help us here. Research has shown that the medication currently available is fairly ineffective. There are two types that can slow down or compensate for the effects of Alzheimer’s.[7] One of them raises the concentration of the neurotransmitter acetylcholine, which is crucial to memory processes. The other reduces the effect of the neurotransmitter glutamate on brain cells. Glutamate is the most important chemical messenger in the brain: it ensures that cells activate one another, and thus supports memory and other cognitive abilities. The theory is that in Alzheimer’s, glutamate is produced in excessive amounts, damaging brain cells. Hence, the medication blocks its activity. Both medications have been used to treat MCI, but unfortunately neither has proved very successful in preventing Alzheimer’s, though one study found a positive effect.
What has been proven to have a positive effect is exercise. This was recently established yet again in a study where subjects with MCI (with an average age of 70) followed an intensive exercise program or gentle stretching exercises. The intensive program aimed to achieve aerobic fitness, and the trainer made sure that the participants’ heart rate rose substantially during the activity. In the aerobics group, the participants had to keep their heart rate between 75 and 85 per cent of the heart-rate reserve — that is, the difference between a person’s maximum heart rate (while running on the treadmill, for example) and resting heart rate. In the control group, doing only gentle stretching, the participants had to keep their heart rate at or below 50 per cent of the heart-rate reserve. The subjects exercised for 45 minutes, four times a week, for six months. Those in the intensive exercise group performed significantly better on a number of tests of cognitive skills compared to the stretching group. The effect was most powerful in the female subjects and primarily in tests designed to measure cognitive flexibility.
We do not know exactly why exercise has a beneficial effect on mental faculties, though better oxygen flow to the brain probably plays a role. There are also indications that intensive exercise promotes the release of growth factors produced by the body, which in turn have a favourable effect on brain cells. We’ll come back to this later. In any event, the Roman proverb ‘a healthy mind in a healthy body’ has lost none of its significance.
But it’s not just physical exercise that matters. Remaining mentally and socially active is essential. A study in Chicago of over 1300 subjects between the ages of 70 and 89 showed that older people who use the computer, play games, read books, and engage in creative activities such as quilting or knitting function better mentally than those who don’t. Approximately 200 participants with MCI proved to have been much less active in this way in the year before the study than the others. Though this is interesting information, it is important to be cautious about the results of a study such as this, since it reveals no causal link. It doesn’t necessarily mean that a less active brain leads to cognitive decline. It could, after all, be the other way round: someone whose mental capacities are declining may engage in less mental activity. And other factors may play a role, too. For example, if you belong to a lower socio-economic class, you may suffer earlier from cognitive deficits, read fewer books, and use the computer less often. Incidentally, the link between mental activity and cognitive decline did not apply to all mental activities. In the Chicago study, the two groups (those with and without MCI) reported reading the newspaper equally often, though it should be noted that many people ‘skim’ the newspaper, and reading a book demands greater concentration, on the whole.
A study on cognitive training showed that being mentally active is accompanied by an improvement in mental capacities. Such training can take a number of forms. The emphasis often lies on exercises such as memory tests or puzzle-solving. Or the emphasis may be on learning strategies to cope with cognitive tasks. One example is the ‘loci method’ for training memory. If you want to remember a shopping list, you imagine placing all the items in a particular space (your living room, for example): a carton of milk on the piano stool, half a wholemeal loaf on the table, and a lettuce on the sofa. It seems like a lot of effort, and it is, but that’s why it works. You recall what you want to buy as you walk around the supermarket while visualising your living room. Various studies have shown that cognitive skills can be trained in people with MCI, improving their performance in tests of attention, memory, and executive functions. And the effects are long-term. If these skills are retested months later, the participants still perform better than before the training. According to some studies, these effects are ‘domain specific’, meaning that if you train yourself to concentrate on pictures, your memory will not improve — just your concentration on pictures. Which in turn would suggest that this kind of training has only a limited effect. Other studies, however, have shown that in some kinds of training the improvement is broader than in just the specific task that has been trained. For instance, if a method for training visual attention involves concentrating on small changes in pictures on a screen, this could also improve attention in traffic situations. This doesn’t mean that people who undergo this type of training are fully competent to drive. Driving in traffic requires other complex skills, such as anticipating and estimating outcomes (both executive functions), and motor co-ordination. The entire complex of skills can best be tested in a driving simulator in a university neuropsychology department.
Besides these computerised exercises, there are other kinds of training that take place in real life and focus on social participation. They take the form of a daily activity that makes demands on your cognitive skills. Interesting findings emerged from a small-scale study in Baltimore in which older people from disadvantaged social groups (low income, low levels of education) participated in a social and educational program. For 14 hours a week, they worked as teaching assistants with preschool children. Before they started, activity in their frontal cortex was measured through fMRI scans (a form of MRI that measures brain activity through changes in blood flow), and this process was repeated after they had been participating in the program for six months. What was the result? Their frontal cortex was more active, and their executive functions (such as cognitive flexibility) had improved in comparison with a group of people of the same age and background who were on the waiting list for the program.
Older people can probably be encouraged to engage in voluntary social work to a greater extent than happens at present. Rudi Westendorp, former head of geriatrics at the Leiden University Medical Centre, argued this in an interview published in de Volkskrant.[8] He pointed out that young people today will probably live to an average age of 90 to 100, while many seniors are still full of life and can make an active contribution to society. ‘When she turned 65, my grandmother announced that from now on she was going to take things easy, but she died at the age of 99,’ said Westendorp. ‘She had to reinvent herself three times over.’ Older people of today and in the future will have many more healthy years of life, he claimed. ‘One voluntary organisation has calculated that older volunteers have provided billions of hours of free informal care this year. Why don’t we convert that into normal, paid work? That way, older people can support themselves for longer and need less pension.’ Not to mention the fact that the risk of developing MCI and Alzheimer’s is probably lower, or at least their onset is delayed, if people can remain active in this way.
The renowned Mayo Clinic in the US, which specialises in research into ageing and the treatment of Alzheimer’s, advises patients to remain physically active, but also to follow a low-fat diet with lots of vegetables and fruit. In addition, it recommends that patients regularly eat oily fish, which contains beneficial omega-3 fatty acids. This may have a positive effect on the heart and thus on the brain. Although these steps can do no harm, it is important to remember that there is substantially less evidence for this view than for the value of physical exercise and mental activity.
IF DEMENTIA DOES STRIKE
Former US president Ronald Reagan was instrumental in opening up discussion on the subject of dementia. In November 1994, he published a letter to the American people announcing that he had been diagnosed with Alzheimer’s. ‘I have recently been told that I am one of the millions of Americans who will be afflicted with Alzheimer’s disease,’ he wrote. ‘At the moment, I feel just fine. I intend to live the remainder of the years God gives me on this earth doing the things I have always done.’ The letter ended: ‘I now begin the journey that will lead me into the sunset of my life. I know that for America there will always be a bright dawn ahead.’ According to his son Ron, Reagan was already showing signs of dementia in 1986 (when he was still president).[9] For instance, while flying over the familiar canyons north of Los Angeles, he could no longer summon up their names. The diagnosis was not officially made until 1994, and he died ten years later, at the age of 93.
Age is the biggest risk factor for dementia. While only 1 per cent of 60-year-olds suffer from it, 7 per cent of 70-year-olds and around 30 per cent of 80-year-olds have one form or another. In Australia, 322,000 people are estimated to be dementia sufferers, a figure that can only grow as the population ages. The Australian Institute of Health and Welfare estimates that it will reach 900,000 by 2050. And according to the World Alzheimer Report 2009, 118 million people worldwide will be suffering from the disease by 2050.
The most common forms of dementia are Alzheimer’s disease, vascular dementia, frontotemporal dementia, and Parkinson’s disease. Alzheimer’s accounts for 70 per cent of cases; vascular dementia, for 15 per cent; while the remaining 15 per cent includes frontotemporal dementia, Parkinson’s, and a few rare types.
In fact, Alzheimer’s can only be reliably established after death, following a pathological examination of the brain. People naturally want an earlier diagnosis so that the right treatment can be started. As a result, every form of dementia that cannot be put down to another cause (for example, where there is no evidence of Parkinson’s or of small brain haemorrhages) is considered for convenience’ sake as Alzheimer’s. Generally, that will be a correct diagnosis, for the simple reason that Alzheimer’s is the most common form of dementia.
In screening for dementia, doctors often administer the mini–mental state examination (MMSE), which samples functions such as memory, orientation to time and place, concentration, and language skills. A maximum of 30 points can be scored on the test, which is easily attainable for most healthy adults. A score of 27–30 is seen as normal, indicating no cognitive disorder. A score of 21–26 may be evidence of MCI or early-stage dementia. Of course, the reason for a lower score may be something completely different, such as depression, which also affects cognitive function. A score of 11–20 indicates moderate dementia, and scores below 10 indicate serious dementia. The MMSE is a short, general test, and in many cases, especially where the patient is suffering from mild impairment, a more extensive neuropsychological examination is advisable.
Short-term memory is the first casualty of Alzheimer’s. If neuropsychological testing is done, it shows that verbal memory (such as recalling lists of words) is the first part of short-term memory to go. Memory problems are followed by a decline in some executive functions (the person may have difficulty planning activities and switching focus) and language problems (he or she may speak in a confused manner). Patients can also suffer from delusions or hallucinations. A delusion is when a person believes something that does not correspond to reality; a hallucination involves seeing or hearing something that isn’t real. An example of a common delusion experienced by Alzheimer’s patients is that a relative has stolen something from them. A hallucinating patient can see people, shapes, or objects that do not exist. In my book Figments of Our Imagination, I go into greater detail about changes in brain functions that can lead to hallucinations and delusions, particularly in psychiatric patients. I also show that they can occur, in a milder form, in healthy people. The parts of the brain involved in such experiences are the prefrontal cortex and the temporal cortex, precisely the areas most severely affected by Alzheimer’s.
Vascular-dementia patients often have a history of (often tiny) brain haemorrhages or bleeding. There is an irregular pattern of cognitive decline that differs from patient to patient. One may primarily suffer from reduced cognitive flexibility or find it hard to plan and co-ordinate activities, another has the greatest difficulty in finding words, while yet another complains mostly of memory problems. This is related to the location of the haemorrhages.
Frontotemporal dementia is signalled early on by behavioural changes, including disinhibition. The part of the brain that is affected is not the hippocampus, as in Alzheimer’s, but the prefrontal cortex, which regulates behaviour and suppresses inappropriate behaviour. Frontotemporal dementia is much less common than Alzheimer’s but tends to occur at a younger age: if a person shows signs of dementia before their 65th birthday, it is more likely to be frontotemporal dementia.
The early stages of Parkinson’s disease are often characterised by motor symptoms, such as trembling hands or difficulty getting out of a chair. Cells deep in the brain that produce dopamine begin to die. Dopamine is a neurotransmitter that influences mood, and the destruction of these cells explains the depression experienced by many Parkinson’s patients.
Alzheimer’s disease can be seen as an extreme form of the ageing process. Damaged neurons and accumulations of tangles and plaques also occur in normal ageing, but in Alzheimer’s the damage is on a much greater scale. Cognitive functions are broken down one by one; memory problems are followed by thinking and language difficulties; and finally patients can no longer speak, walk, or make contact with others, and they become incontinent. This process takes years. Sometimes, as in the case of Ronald Reagan, it can take decades.
Most Alzheimer’s patients at some point end up in a nursing home because their relatives can no longer care for them. An important question is what effect this has on their brains. Unfortunately, little research has been done into this issue. Although placing them in a home may often be the best thing for patients, it seems highly likely that this is not good for their brains. Admission to residential care is often accompanied by a reduction in physical exercise and mental stimulation. That needn’t be the case: many nursing homes are now providing more activities for their residents, but the problem is often lack of staff. Family and friends could play a greater role in involving patients in stimulating activities.
The treatment for Alzheimer’s consists of medication to combat cognitive decline, though the effect is only moderate. At the same time, behavioural therapy can help alleviate restlessness, sleep problems, anxiety, and aggression. The medication for Alzheimer’s was described earlier in this chapter: drugs that reinforce the neurotransmitter acetylcholine or block the activity of glutamate. However, Professor Peter De Deyn, director of the Alzheimer’s Centre at the University of Groningen since 2011, points out that this is merely symptom relief. Researchers worldwide are engaged in discovering the roots of the disease and finding ways to combat it, focusing on anti-inflammatory agents and medication that might reduce or prevent the protein build-up. Some success has been achieved in animal trials, but there has been no breakthrough where human subjects are concerned.
The breakdown of cognitive function in dementia is appalling to witness. Nevertheless, researchers at Alzheimer’s centres in Nijmegen and Maastricht have recently urged us to see dementia in a more positive light.[10] They say that Alzheimer’s is nothing more than an accumulation of phenomena associated with ageing that occur in healthy older people too, though to a lesser extent. Alzheimer’s patients are above all our fellow human beings, rather than ‘sick people’. In The Old King in his Exile, written by the Austrian author Arno Geiger about his father, he describes how life with Alzheimer’s can still be meaningful and valuable, for both patient and relative.
To summarise: doctors and psychologists are now able to diagnose what is possibly a precursor of Alzheimer’s disease. This early stage involves memory problems confirmed by someone close to the person in question. In 50 per cent of cases, the person does not go on to develop Alzheimer’s. In those who do develop it, the hippocampus, an area of the brain vital to memory, is affected. Cognitive training and physical exercise can help slow decline. A major factor in Alzheimer’s is the build-up of protein deposits in the brain. There is as yet no effective treatment, but medication and support can delay the deterioration to some extent.[11]
IMPORTANT INSIGHTS