June 25, 2004 SCOTTSDALE, Ariz. – Research published in the June 8 edition of Neurology, the official journal of the American Academy of Neurology, has determined that, in those with a genetic risk for Alzheimer’s disease, an early decline in memory loss may be detected prior to the symptoms of the disease appearing later in life. This link was strongest in those testing positive for APOE e4, a known genetic marker of predisposition to Alzheimer’s, and was seen more than 10 years prior to the average age of symptomatic diagnosis of the disease, in many cases in those in their 50s.
The study was authored by Richard Caselli, M.D., chair of the Department of Neurology at Mayo Clinic in Scottsdale, along with researchers from Mayo Clinic in Jacksonville, Banner Health Systems, Arizona State University and the Barrow Neurological Institute. Research was conducted locally in Arizona using 212 cognitively typical individuals who had a parent or sibling with Alzheimer’s disease. Testing was done to determine whether they were carriers for the APOE e4 gene. Between the carriers and non-carriers, there were no significant differences on any cognitive or depression measure at the beginning of the study, but over time these measures worsened significantly more in the group of carriers. Most importantly, this decline was evidenced 10-20 years prior to the typical age that patients tend to become symptomatic, showing up at an earlier age than prior studies have shown.
“We’ve known for years that memory becomes less effective with age,” says Dr. Caselli. “Now, we’re looking at this information through the lens of genetics. This finding shows that the biologic onset of neurodegenerative disease may happen many years before the symptomatic presentation. Novel insights such as this can help to redirect research into the realm of pre-clinical prevention.”
Mayo Clinic in Scottsdale is a member institution of the National Institutes of Health (NIH)-funded Arizona Alzheimer’s Disease Center. Future research will be focused on other early indicators, such as inflammatory markers, amyloid and changes in mitochondria in addition to looking at the development of cognitive and behavioral changes at an even earlier age, perhaps in the 40s or even 30s. Imaging techniques such as PET scans may even be able to pick up subtle shifts earlier than neuro-psychological testing. The results of research such as this will be used to design primary prevention therapeutic trials aimed at those of greatest risk for developing the disease at the earliest possible time.
“Although this research has implications for those at risk for Alzheimer’s disease, it’s important to keep in mind that memory ‘incidents’ such as forgetting where you left your keys in and of themselves do not necessarily mean a person will develop Alzheimer’s,” cautions Dr. Caselli. “Neither does the genetic marker itself. However, both of them combined could indicate a predisposition. Knowing that, we can put more efforts into prevention at an even earlier age.”
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