When I started training in psychiatry in the late 1980s my plan was to specialise in child and adolescent disorders. Instead, I was drawn into a research project examining mental illness in older people living at home. That in turn drew me into a peculiarly British speciality, the psychiatry of old age. (As far as I am aware, only the British Isles, Australia, New Zealand and the Netherlands have developed this as a separate discipline within psychiatry.)
In the 1980s our textbooks still referred to senile and pre-senile dementia as though some conceptually important difference existed between dementia occurring before and after 65. In the intervening two decades the public relations machine which supports medicine, pharmaceutical research and voluntary organisations (like the Alzheimer’s Society) has helped to relaunch and publicise a newly-packaged bundle of concepts. Rebranding senile dementia as something largely equivalent to Alzheimer’s disease was one of the most important of these. Calling it a disease tapped into our fascination with all things medical and raised the public discussion to a new level of sophistication.
The successful relaunch of dementia as Alzheimer’s disease was based on several simplifications. One was the “war” declared by the pharmaceutical industry (and related researchers) on Alzheimer’s disease which focused on eliminating the plaques and tangles which accumulate in the brains of those people who eventually suffer the clinical entity known as Alzheimer’s.
This generation of medicines is in a trial phase and none is even close to reaching the market. Some have been ineffective, some produced unacceptable side effects and some were quite simply disastrous. A vaccine which recruited the body’s own immune system to attack and eliminate amyloid plaques was trialled about ten years ago; it caused death and disability in a number of trial participants, mostly in France, where some powerful families had used their influence to get their relatives into the trial. This particular line of research has more or less dried up.
One of the important questions asked around the time of the disastrous vaccine trial was whether the removal of these plaques from the brains of people with Alzheimer’s disease actually resulted in any recovery of lost ability. The answer overall was little if any, just as clearing away the ruins of a city like Berlin or Dresden did not by itself reconstruct the city. In other words, treating Alzheimer’s disease once dementia is already well established might be too late.
Dr Denise Park of the University of Texas was interviewed in February on the Today programme. Her team had scanned a large number of elderly people using an expensive and relatively new technique. This enables researchers to measure the amount of amyloid plaque in the brains of living people. Beta amyloid protein has long been considered one of the basic causes of Alzheimer’s disease. The reason she was being interviewed was to describe the surprising results of her research: although 20 per cent of the subjects in her trial had large amounts of beta amyloid in their brain they were not displaying any signs of dementia.
This lack of a neat correlation between the amount of beta amyloid and the severity of dementia has long been apparent to researchers, but I was astonished to see it entering the consciousness of popular science.
It is beginning to dawn on the researchers that even if an agent was found to be effective against the plaques or tangles it would probably need to be administered when these proteins begin to form in the brain and the evidence is that this happens up to 40 years before the onset of symptoms. Research has now moved in the direction of early detection and has mobilised an array of high-tech gadgetry directed at brain imaging and analysing cerebral spinal fluid for traces of the two offending proteins. In Sweden, for example, a person undergoing investigation for suspected dementia will routinely have a lumbar puncture in order to analyse the cerebral spinal fluid. Enhanced scans can also provide pictures not only of the detailed structure of the brain but also of how particular regions are functioning in terms of consumption of oxygen or glucose, and the presence or absence of beta amyloid.
Alzheimer’s disease is entering the world of what Americans call “gee-whiz” medicine (high tech, high cost) but it is difficult to know yet whether the added cost results in improved accuracy. A question frequently asked in my clinics is whether mildly impaired memory in a person in their seventies or eighties is or is not going to progress to the full disabling and ultimately fatal condition we know as Alzheimer’s disease. If 20 per cent of people can carry heavy beta amyloid loads in their brains without detectable dementia then perhaps these tests may mislead too many people to be useful in an everyday clinical setting. If two out of every ten people you tell are on their way to developing Alzheimer’s disease turn out not to be then the reputation of this approach would soon be in tatters.
If plaques and tangles are indeed the root cause of Alzheimer’s disease then the fact that some people have severe symptoms yet very few tangles, while others have no symptoms but a lot of them, needs to be investigated.
In the US a neurologist, David Snowdon, studied ageing and the onset of dementia in 678 Roman Catholic nuns. The population has been followed since the late 1980s and as the nuns died their brains have been examined. On joining the order in their early twenties all the nuns provided autobiographical sketches. These little essays were categorised according to what is sometimes called “idea density”, which includes concepts such as linguistic complexity, vivacity and fluency. Roughly 80 per cent of those nuns whose essays were found to be low in idea density went on to develop dementia in old age, while only 10 per cent of those who were rich in this quality developed the disease. Another longitudinal study being carried out in Chicago has recently published findings linking the density of a person’s social network to their vulnerability to plaques and tangles. At post mortem it was found that the individuals with dense social networks were less severely demented than their counterparts with smaller social networks even though they had the same tangle density in their brains.
My team has studied a group of people with established dementia living in nursing homes and compared their personality characteristics with those of their unaffected siblings. The striking difference between the two groups was that those with Alzheimer’s disease were much more likely to be solitary, anxious or dependent in terms of lifelong personality traits. This evidence seems to support the existence of a personality-based quality that makes some individuals more, or less, susceptible to the onslaught of plaques and tangles. In balancing the equation between disease (plaques and tangles) and susceptibility (personality) this second ingredient is the one that requires more weight, clinical attention and research.
When I try to diagnose a dementia I explain to the patient and family that usually the least important step in gathering evidence is the brain scan. They never believe me. The same simple faith in technology will need a counterbalance if we are to predict accurately those likely to benefit from beginning early treatment. I predict that that counterbalance will be found by identifying factors unique to the individual, such as personality.