Living with Dementia September 2008

The world's largest conference on dementia research took place in Chicago in July. The Society's Head of Research Dr Susanne Sorensen reports on some of the highlights from the International Conference for Alzheimer's Disease.

I had the privilege of joining 5,500 scientists, clinicians and people working in the field of dementia in Chicago in July to hear about the latest findings in dementia research from experts in the field.

The conference centre was on the edge of Lake Michigan and the weather was lovely with clear blue skies every day, but we all assembled in dark rooms to hear the latest on tangles and plaques*, the outcomes of clinical trials, studies on brain tissue and on how the choices made throughout life influence our risk of getting dementia.

The delegates work hard during these conferences. The days are long and smaller groups often carry on into the night with extra meetings. It was impossible to hear everything.

In total, around 450 oral presentations were made during the conference and there were a further 2,000 poster presentations. Was I more interested in outcomes from clinical trials of new drugs or methods of diagnosis? Would I prefer to hear the latest data from a study linking clinical symptoms to observations in post mortem tissue or attend a session on inflammation's role in the development of dementia? Choices had to be made!

Exciting advances

Some of the main developments that emerged for me include:

• The location and amount of tangles in the brain correlate better with clinical symptoms of dementia than the location and amount of plaques. So, if we are looking for treatments for the symptoms, tangles may be a good target. This is in contrast to research efforts in the last ten years which have focused on the amyloid cascade*, both in the understanding of the disease and as a target for treatment (*the amyloid cascade refers to the series of molecular events involving amyloid proteins that lead to the development of plaques).
• There is probably much more overlap between the different diseases that cause dementia in older people than previously thought. An American researcher presented results from a large study indicating that 60 per cent of people dying with dementia actually had mixed dementias (with a large range of combinations of Lewy body, vascular and Alzheimer's characteristics).
• Many researchers are working on developing a blood test for Alzheimer's by identifying molecules in the blood that increase or decrease in concentration as the disease develops. There seemed to be more than one successful direction of travel in this area. However, it still looks as though it will be some years before a blood test may become available.
• The neurological diseases that cause dementia develop silently for many years before the symptoms of dementia begin. The long-term objective of much research now is to find methods of identifying the people who may develop clinical dementia before the symptoms appear. This would mean that potential preventative drugs could be clinically trialled on the optimal group of people.
• Many genes may be involved in increasing the risk of dementia by a tiny amount each.
• The ApoE gene and protein (the only gene confirmed to increase the risk of developing Alzheimer's disease) is finally receiving attention and we may soon understand why a particular variant of this gene (ApoE4) increases the risk of developing dementia considerably.
• Exciting new scanning techniques are being developed that make it possible to 'see' plaques and tangles in the brain.

Rember
Many sessions were taken up with discussion of clinical trial design and presentations of new data from clinical trials. It was interesting to note that there are now several potential drugs being put forward that target other processes than the amyloid cascade, which has been the focus for new drug development for the last 15 years.

One of these made headlines across the UK; RemberTM. The basic research leading to the development of this drug, which targets tangles, was carried out in Scotland. The data from the Phase II trial looked promising with Rember slowing the rate of cognitive decline by as much as 81 per cent on some rating scales. However, it is worth remembering that one in five drugs coming through a phase II trial fails in phase III trials.

It takes two successful phase III trials to licence a new drug. Additionally, many scientists present at the meeting seriously questioned some of the data, pointing out that it was difficult to make sense of the presentation of the side effects of the drug. As the drug colours the urine blue/green, it is difficult to run a truly blinded trial . Many other scientists will now examine the data and seek to replicate the results. Only if other scientists can explain how this drug works and get the same results will we know we have a new treatment for Alzheimer's disease. 

Clinical trials
A considerable amount of time was taken up with discussion about the design of clinical trials. There are significant problems with clinical trials for people with dementia. For example, researchers may have identified potential drugs to treat dementia from effects noted on people taking the drug for another condition; in this case non-steroidal anti-inflammatory taken to alleviate pain in arthritis.

However, the effective 'treatment window' in a clinical trial may be before the symptoms of dementia appear. This makes it impossible to identify and recruit people to take part in a trial of this drug for dementia at this point in time. The same may be the case for potential dementia drugs developed in laboratory studies. These may have all the attributes expected of an effective dementia drug, but again, may not be effective once the symptoms have already appeared.

Catching people early
There was a consensus amongst many delegates that finding ways of identifying people who are likely to get dementia, and developing methods to monitor the 'silent' diseases in order to study the effects of potential drugs, should be a priority in the coming years.

Other problems associated with the design of drug trials for dementia is that it may not actually be possible to reverse the damage in the brain once it is quite advanced. The desired outcome would be to find a way of stabilising a person's cognition and halting the deterioration. However, this requires lengthening clinical trials, which has serious cost implications.

Impressions
The conference presented some disappointments, such as the failure of drug trials to produce new and better drugs. But it also generated tremendous excitement and hope for the future. We now understand that dementia in older people is very complex and that we need more than one type of therapy. In response to this, several new avenues are being followed.

It is also becoming clearer that most of us can do something ourselves to reduce our risk of developing dementia. The evidence keeps building that treating high blood pressure, eating a healthy diet that includes fish and plenty of fruit and vegetables and moving that body throughout life is likely to help us achieve good health in old age. 

The next ICAD conference will take place in Vienna next July 2009.