Light on dementia

Alzheimer’s disease is by far the commonest form of dementia affecting around 5 per cent of all people over the age of 75. There is still no cure but research has shown that loss of higher brain functions is associated with deposition of a protein called amyloid which, in Alzheimer’s disease folds into an aberrant shape to form insoluble fibrils.

What is less well known, however, is how the disease starts and progresses. People are usually diagnosed long after the disease takes hold when the symptoms of memory loss and disorientation become impossible to ignore. By the time a diagnosis has been made the brain has already lost many cells.  At the point of death, someone with Alzheimer’s disease has typically lost 25-30 per cent of his or her brain volume.

The latest Magnetic Resonance Imaging (MRI) scanning technology, combined with new techniques of image processing could help to change all that, however. Members of the Dementia Research Group based at London’s Institute of Neurology have developed a system called voxel-compression mapping which picks up the earliest brain changes that characterise degenerative brain disorders like Alzheimer’s. As the disease takes hold, its progression can be monitored in minute detail. This makes a welcome change from the current method of comparing and contrasting scans using nothing but the naked eye.

Dr Nick Fox, author of a paper on the subject published in a recent issue of Proceedings of the National Academy of Science, came up with the idea of registering MRI to track changes due to AD.  “It can be extremely difficult to detect changes in brain scans over time,” he explains. “Neuroradiologists do an amazing job picking up an abnormality that shouldn’t be there but the eye is not so good at quantifying change over time. Computational methods of assessing brain scans seemed the way forward.”

First, the patient’s brain is scanned using high-resolution MRI. (MRI picks up signals from different types of fluid in the body and creates a very detailed map of tissue types. Usefully, it sees through essentially “dry” bone and can peer through the skull with no problem.) The programme works by utilising all voxels in a three-dimensional or volume image.  (A voxel is basically the three-dimensional equivalent of a pixel.) A second image, taken some time later, is then compared to the first. The computer begins by matching up the image as precisely as possible. Essentially, it compares the two images voxel by voxel and jiggles them around until it gets the best possible fit.

When the best match has been made, the programme analyses the voxels, which do not fit, registering how much each has been squeezed or stretched.  These data are converted into a spectrum of colours. Areas where there is significant tissue loss are colour coded in blue. Fluid-filled cavities, which are expanding, are colour coded in red. Each voxel also has a number so it is possible to see tissue loss in a particular area no more than a thumbnail thickness.

Voxel-compression mapping has already been used to back up studies that suggest that Alzheimer’s starts in the hippocampus, the area of the brain, which controls recent memory. It has also been used to identify earliest structural brain changes in people who have a genetic predisposition to developing early-onset Alzheimer’s disease but have not yet suffered any clinical symptoms.

Dr Fox is hoping that MRI scans will one day allow him to see protein accumulation itself. “At the moment, we see the effects of that protein accumulation and cellular damage. Ultimately, we would like to see it directly, rather than the consequences.” This would mean that researchers could test drugs and see if they have an effect at a cellular level.