Dementia 'clue' in the young

Tuesday April 7 2009

The Daily Telegraph has reported that “young people could be screened for Alzheimer's risk”. It said that brain scans of young people found that those carrying a ‘faulty’ gene had changes in brain activity ‘decades before any symptoms of dementia might occur’. The newspaper said that experts have called it the first step towards a diagnostic test to see who is at risk of the disease.

It is known that people who carry one or more copies of the E4 variant of the APOE gene are at higher risk of developing Alzheimer’s. However, not all E4 carriers will develop the disease and not all people who have Alzheimer’s carry the E4 form of the gene. As such, it is still not possible to predict who will get Alzheimer’s from a young age.

Although this study itself does not aid in identifying those E4 carriers who will go on to develop Alzheimer’s, its results may pave the way for a study that could do this. Such a study would need to follow people over an entire lifetime so it will probably be some time before it is known whether brain scans in early life can help predict which E4 carriers will develop Alzheimer’s.

Where did the story come from?

Dr Nicola Filippini and colleagues from the University of Oxford, GlaxoSmithKline and other research centres in the UK and Italy carried out this research. Data acquisition was funded by GlaxoSmithKline. The study was published in the peer-reviewed medical journal, Proceedings of the National Academy of Sciences of America .

What kind of scientific study was this?

This cross-sectional study compared brain activity (measured by a functional MRI brain scan) in young people carrying a particular variant of the APOE gene with those who do not carry this variant. It is known that people who carry the E4 form of the APOE gene are at greater risk of developing Alzheimer’s disease than those who do not. Although studies have shown that carrying an E4 variant is associated with effects on the structure, metabolism and function of the brain, it is not clear at what age these differences arise.

The researchers were particularly interested in several areas in the brain that are often activated together when the brain is at rest, called the ‘default mode network’ (DMN). This network is made up of well-defined areas of the brain. These include the prefrontal, anterior and posterior cingulate, lateral parietal, and inferior/middle temporal gyri, cerebellar areas, thalamic nuclei and mesial temporal lobe (MTL) regions. In Alzheimer’s disease, nerve cells in these areas are known to degenerate. The researchers were also interested in whether there were any differences in brain activity when a person was involved in a mental task. They chose a specific memory task that involved the MTL regions and hippocampus, as these are the areas that first show damage in Alzheimer’s disease.

The researchers enrolled 18 healthy people aged 20 to 35 years old who carried one copy of the E4 form of the APOE gene. They also enrolled 18 healthy people who did not carry any copies of the E4 form of the APOE gene, and who were matched to the carriers for sex, age and years of education. Two people in each group had a family member with dementia.

The participants were placed in a functional MRI (fMRI) machine and their brain activity scanned while they were at rest. In this type of brain scanning, more active areas of the brain are identified based on their use of oxygen. The participants’ brains were also scanned while they carried out the memory task. The researchers then compared the two groups of people at rest and during the memory task.

What were the results of the study?

The researchers found that some regions of the DMN network in the brain were more active in E4 carriers than non-carriers at rest. The E4 carriers performed equally well on the memory task as the non-carriers. During the memory test, brain scans showed E4 carriers to have more activity in the hippocampus and some other areas than non-carriers. There were no regions in the E4 carriers that were less active than non-carriers at rest or during the memory task. There were no obvious differences between the groups in brain structure or in blood flow to the brain identified by the fMRI scan.

What interpretations did the researchers draw from these results?

The researchers concluded that the E4 form of the APOE gene affects brain function decades before there is evidence of degeneration in the brain.

What does the NHS Knowledge Service make of this study?

This relatively small study demonstrated that differences in   brain activity patterns can be seen in healthy young people    who carry a copy of the E4 form of the APOE gene compared to non-carriers.

It is already known that people who carry one or more copies of the E4 variant of the APOE gene are at greater risk of developing Alzheimer’s but not all carriers develop the disease. At present, the results of this study do not help us to differentiate the E4 carriers who will go on to develop Alzheimer’s from those who will not.

However, its results may pave the way for a study that could do this. Such a study would need to look at brain activity in young carriers of the E4 variant, and follow them up over time to see who developed Alzheimer’s to see if there had been any clear differences between those who developed the disease and those who did not. This research would take a long time to complete, as it would have to follow people over an entire lifetime. The balance of benefit and harm, and the ethics of identifying those who may go on to develop Alzheimer’s would need to be debated before any such screening was widely introduced, especially as there is currently no way of stopping a person from developing the disease.

Analysis by Bazian
Edited by NHS Choices