Brain Scans Show Young Adults at Future Risk of Alzheimer's have Different Brain Activity

Young adults with a genetic variant that increases their risk of developing Alzheimer's disease (AD) show changes in their brain activity decades before any symptoms might arise, according to a recent brain imaging study. The study's findings may support the hypothesis that the brain's memory function may gradually wear itself out in those who go on to develop AD.

Scientists from the University of Oxford (UK) and Imperial College London (UK) utilized functional magnetic resonance imaging (fMRI) scans on 36 healthy volunteers between the ages of 20 and 35, 18 of whom carried at least one copy of the APOE4 gene.

One-quarter of the wider population have the APOE4 genetic variant, which increases by up to four times the normal risk of developing Alzheimer's later in life, while those with two copies of the gene are at up to 10 times the normal risk. The study, published in the April 7, 2009, issue of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS), is the first to show hyperactivity in the hippocampus area of the brains of healthy young carriers of APOE4.

Rebecca Wood, chief executive of the Alzheimer's Research Trust (Cambridge, UK), said, "This significant development takes us a step closer to accurately predicting who will develop Alzheimer's before any symptoms become apparent. However, we are not yet at that stage; those with the APOE4 genetic variant--while at a statistically higher risk of developing the disease than others--will still not develop Alzheimer's in most cases. The causes of Alzheimer's are complex--both genetic and environmental--and if we can understand these better, we can enhance efforts to help people lower their risks. We can reduce our risk of developing dementia by maintaining a balanced diet, exercising regularly, and keeping our brains active, particularly through social activities. Alzheimer's and other dementias affect 700,000 people in the UK, costing our economy GBP 17 billion annually. Much more research is needed if we are to stop these figures from spiraling."

Dr. Clare Mackay, the lead author of the study from the department of psychiatry and the Center for Functional Magnetic Resonance Imaging of the Brain at the University of Oxford, said, "We have shown that brain activity is different in people with this version of the gene decades before any memory problems might develop. We've also shown that this form of fMRI, where people just lie in the scanner doing nothing, is sensitive enough to pick up these changes. These are exciting first steps towards a tantalizing prospect: a simple test that will be able to distinguish who will go on to develop Alzheimer's."

Dr. Christian Beckmann, another author of the study from the division of neurosciences and mental health at Imperial College London, added, "Our brains are always active--our minds wander even when we're not carrying out specific tasks. We were surprised to see that even when the volunteers carrying APOE4 weren't being asked to do anything, you could see the memory part of the brain working harder than it was in the other volunteers. Not all APOE4 carriers go on to develop Alzheimer's, but it would make sense if in some people, the memory part of the brain effectively becomes exhausted from overwork and this contributes to the disease. This theory is supported by studies that have found the opposite pattern in people who have developed Alzheimer's, with these people showing less activity than normal in the memory part of the brain."

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University of Oxford
Imperial College London