July 5, 2011
Increasingly, researchers are thinking of Alzheimer’s as a disease that begins years before the onset of memory loss and thinking problems become obvious. Now, they are moving closer to a blood test that can predict mental decline, and possible Alzheimer’s, at an early stage.
A simple and easy test that would diagnose Alzheimer’s disease at an early stage is important, since drugs may be most effective when given before damage to the brain becomes extensive. Early diagnosis would also allow patients and family members to plan better for the future.
A blood test would also be cheaper and easier for initial screening than more advanced tests like brain scans. If blood tests indicated a patient showed signs of being on the road to developing Alzheimer’s, more advanced studies could then be carried out to confirm the diagnosis.
In the latest findings, researchers at the University of California, San Francisco, and the San Francisco Veterans Affairs Medical Center measured levels of beta-amyloid in the blood of healthy older people who did not have Alzheimer’s disease. Beta-amyloid is a protein that is normally present in the brain, but that can be cleaved into toxic fragments.
Some of these fragments move out of the brain and into the spinal fluid or the blood. But if this process is blocked, beta-amyloid fragments accumulate in the brain, where they form clusters called plaques that damage cells in the brain’s memory centers. At the same time, beta-amyloid levels in the blood decrease. So the lower the beta-amyloid levels in the blood or spinal fluid, the higher they are in the brain, potentially giving rise to the characteristic damage of Alzheimer’s disease.
Earlier studies have suggested that low levels of beta-amyloid in the blood or spinal fluid may be linked to a higher risk of Alzheimer’s. This study, published in the Journal of the American Medical Association, was longer term than many previous studies, lasting for nine years. It also involved a large number of healthy seniors, 997 healthy men and women living in the San Francisco area whose average age was 74 at the start of the study, in 1997. All were given regular mental exams and beta-amyloid blood analyses.
The researchers found that those with the highest blood levels of beta-amyloid were least likely to have declines in their memory and thinking skills. Those with the lowest levels were at the greatest risk of cognitive problems.
Other factors, though, also played a role. Among those who had low levels of the protein, memory and thinking problems were most severe in those who had the least formal education and reading ability. The finding is consistent with the cognitive reserve theory, which holds that education and mental stimulation help develop a rich network of brain cells that is better able to ward off memory loss and other symptoms of Alzheimer’s disease.
In addition, people who had the APOE-E4 gene, which is linked to an increased risk of Alzheimer’s, seemed to be at a greater risk of a mental decline even if their blood levels of beta-amyloid were high.
The researchers call for additional studies to determine the relationship between blood beta-amyloid levels and Alzheimer’s risk. Further refinement and testing is needed before a blood test will be available in doctors’ offices.
Kristine Yaffe, MD; Andrea Weston, MPH; Neill R. Graff-Radford, MBBCh; et al: “Association of Plasma β-Amyloid Level and Cognitive Reserve With Subsequent Cognitive Decline.” Journal of the American Medical Association, Vol. 305 (No. 3), January 19, 2011, pages 304-305.