Finding a reliable, affordable and relatively non–invasive way to accurately diagnose Alzheimer’s disease before the clinical symptoms develop is something many researchers have been investigating over the last few years.
PET scans (Positron Emission Tomography) have looked promising because they can show beta amyloid deposition in living brains. This has led to the hope that PET scans could be used as a predictive test, to determine who is at greater risk of developing cognitive impairment.
Professor Christopher Rowe from Austin Hospital, Victoria, Australia has led the way in this. Some of his latest research was presented earlier this year from a study on 366 subjects (average age 72 years). Of the group, 195 were healthy controls, 92 had mild cognitive impairment (MCI) and 79 had Alzheimer’s disease.
The group underwent PET scanning at the start of the study and again at 20 months and 36 months. In addition they also underwent 3D MRI scanning and had a full clinical and neuropsychological assessment at each visit.
The findings revealed that those of the healthy controls who were found to have amyloid deposition in their brains at the start of the study, and those with the greatest amount of beta amyloid plaques were the most likely to develop cognitive impairment.
Of those with MCI or Alzheimer’s disease, they were shown to have smaller volume hippocampi – the specialised area of the brain associated with learning and memory, and an area known to be affected early in Alzheimer’s disease.
On the PET scans, 98% of the subjects with Alzheimer’s’ disease were found to have a high level of beta amyloid in their brains, compared to 63% of those with MCI and 34% of the healthy controls.
Two years later it was possible to see from the follow-up scans, that healthy controls with beta amyloid deposition showed greater grey matter loss in the hippocampus and greater levels of mild memory decline.
Prof Rowe has stated he believes that the presence of beta amyloid in the brain signifies that person has a greater risk to future cognitive decline. He also said that carriers of the gene apoE4, a known risk factor for Alzheimer’s disease and vascular dementia, also showed a higher risk for cognitive decline on scans.
Because brain changes such as amyloid deposition occur at least 10 years prior to the onset of clinical symptoms, it is hoped that these imaging techniques will make it possible to identify the disease early enough for more effective treatments to be started.
In addition to PET scans, now a new form of MRI has also been shown to provide an early and reliable tool for predicting who is at greatest risk of cognitive decline.
Arterial spin labelling (ASL) is the technique which is being used to examine changes in brain function. The brain uses glucose primarily as its energy source. Changes in brain blood flow and the rate of consumption of glucose by the brain can be seen as changes in brain function using this technique.
MRI on its own provides a structural assessment to look at changes in the brain. In the diagram at the top of the page, the grey images on the left are from traditional MRI scans. Adding this new technique at the same time as a regular MRI allows a rapid assessment of brain function as well. This obviously saves the time and expense of otherwise having to wait for a PET scan, which is also very expensive.
In one recent study the investigators looked to see whether ASL-MRI or PET scans would be the better technique to use as a way to look for evidence of Alzheimer’s disease. In a group of 31 subjects (18 were healthy controls and 13 had Alzheimer’s disease) no demonstrable difference was noted in using either of the two tests.
In a second study in a similar size group, computer analysis of brain pattern blood flow and glucose metabolism again showed similar findings from both techniques.
The advantage of ASL-MRI however, is that it is non invasive, has no associated radiation exposure, and could be easily incorporated into existing MRI machines which are comparatively readily available. Further studies will continue to evaluate the usefulness of this as a potential screening and follow up investigative tool. It could be that ASL-MRI will provide the advantage, but PET may still be useful as an extra diagnostic tool where there is clinical uncertainty.
1. Erik S. Musiek, Yufen Chen, Marc Korczykowski, Babak Saboury, Patricia M. Martinez, Janet S. Reddin, Abass Alavi, Daniel Y. Kimberg, David A. Wolk, Per Julin, Andrew B. Newberg, Steven E. Arnold, John A. Detre. Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer’s disease. Alzheimer's and Dementia, 2011; DOI: 10.1016/j.jalz.2011.06.003
2. Y. Chen, D. A. Wolk, J. S. Reddin, M. Korczykowski, P. M. Martinez, E. S. Musiek, A. B. Newberg, P. Julin, S. E. Arnold, J. H. Greenberg, J. A. Detre. Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease. Neurology, 2011; DOI: 10.1212/WNL.0b013e31823a0ef7
3. Christopher C. Rowe, et al. Cognition and beta-amyloid in preclinical Alzheimer's disease: Data from the AIBL study, Neuropsychologia, Volume 49, Issue 9, July 2011, Pages 2384-2390, ISSN 0028-3932, 10.1016/j.neuropsychologia.2011.04.012.
Credit for Image: Alzheimer's & Dementia: The Journal of the Alzheimer's Association