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Mayo Clinic Study Finds Earliest Evidence of Memory Decline in Middle-Aged People at Genetic Risk for Alzheimer's Disease

SCOTTSDALE, Ariz., July 15 /PRNewswire-USNewswire/ -- Memory lapses that occur with normal aging are a source of worry for many who fear Alzheimer's disease. Now a new Mayo Clinic-led study published in the July 16 issue of the New England Journal of Medicine suggests that the carriers of a common genetic risk factor for Alzheimer's disease begin to have memory declines in their mid-50s, far earlier than previously thought.

These and other findings reported by researchers and their colleagues in the Arizona Alzheimer's Consortium support the possibility that future Alzheimer's treatments may be most effective if started in middle-aged people, years before the onset of disabling memory and thinking problems or extensive brain pathology.

The study, which followed participants for up to 14 years, used sensitive memory and thinking tests to detect, track and compare cognitive performance in 815 healthy people, 21 to 97 years of age, with two copies, one copy and no copies of the APOE e4 gene, the major genetic risk factor for developing Alzheimer's disease at older ages. Each additional copy of this gene is associated with a higher risk of Alzheimer's disease and a slightly younger age at the onset of clinically significant memory and thinking problems.

Approximately one out of four people have one copy of the APOE e4 gene, which was inherited from one parent, and about 2 percent have two copies, which were inherited from both parents.

"We found that memory declines begin to differentiate groups of people at these three levels of genetic risk starting between ages 55 and 60, years earlier than previously suspected, and well before the anticipated onset of clinically significant symptoms," said Richard J. Caselli, M.D., Chair of Mayo Clinic's Neurology Department in Arizona and lead author of the research study. "While other age-sensitive cognitive skills also change, memory, specifically, appears to decline more quickly in APOE e4 gene carriers, and it is this pattern of cognitive aging that is similar to (but much milder than) what we expect to see in patients with Alzheimer's disease. This suggests that seemingly normal age-related memory loss may actually represent very early, preclinical-stage Alzheimer's disease."

The study was performed in collaboration with researchers from several other institutions in the Arizona Alzheimer's Consortium, including ArizonaStateUniversity, Banner Alzheimer's Institute, Barrow Neurological Institute, Sun Health Research Institute, Translational Genomics Research Institute and the University of Arizona. It was supported by research grants from the National Institute on Aging and the state of Arizona.

Using brain-imaging techniques to study some of the same individuals in a previous study, the researchers reported brain changes in people at three levels of genetic risk, some of which appear decades before the onset of symptoms. They have suggested the importance of conducting prevention trials starting in late middle-age, and also suggested how brain-imaging techniques could be used to evaluate these treatments without having to study thousands of people or wait many years to see which people go on to develop symptoms.

"The current findings provide new information about the cognitive declines associated with normal aging and the extent to which they are accelerated by the major genetic risk factor for Alzheimer's disease," said Eric Reiman, M.D., Executive Director of the Banner Alzheimer's Institute, Director of the Arizona Alzheimer's Consortium, and one of the study authors.

"Perhaps more important, these findings add to the evidence that certain Alzheimer's treatments may be most effective if started not only before people develop symptoms, but even before they reach older ages."

"This study highlights the idea that Alzheimer's disease is a progressive disorder that likely begins well before clinical diagnosis," said Creighton Phelps, Ph.D., who directs the Alzheimer's Disease Research Center program for the National Institute on Aging. "Additional research is needed to identify those at high genetic risk and develop methods to delay disease progression."

Alzheimer's disease afflicts about 10 percent of people over age 65 and almost half over 85. With the skyrocketing number of people living to older ages, there is an urgent need to find demonstrably effective Alzheimer's prevention therapies. The researchers do not recommend using brain imaging or cognitive tests to predict a healthy person's risk for developing Alzheimer's later in life. But they are excited about the chance to use these techniques in cognitively normal carriers of the APOE e4 gene to evaluate promising Alzheimer's prevention therapies as quickly as possible.

To arrange an interview with Richard J. Caselli, M.D., please call (480) 301-4222 during business hours and 602-291-2505 after hours.

About Mayo Clinic

Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. As a leading academic medical center in the Southwest, Mayo Clinic focuses on providing specialty and surgical care in more than 65 disciplines at its outpatient facility in north Scottsdale and at MayoClinicHospital. The 244-licensed bed hospital is located at 56th Street and Mayo Boulevard (north of Bell Road) in northeast Phoenix, and provides inpatient care to support the medical and surgical specialties of the clinic, which is located at 134th Street and Shea Boulevard in Scottsdale. To obtain the latest news releases from Mayo Clinic, go to For information about research and education visit ( is available as a resource for your health stories.

About ArizonaStateUniversity

ArizonaStateUniversity is a creating a new model for American higher education, an unprecedented combination of academic excellence, entrepreneurial energy and broad access. This NewAmericanUniversity is a single, unified institution comprising four differentiated campuses positively impacting the economic, social, cultural and environmental health of the communities it serves. Its research is inspired by real world application, blurring the boundaries that traditionally separate academic disciplines. ASU serves more than 64,000 students in metropolitan Phoenix, Arizona, the nation's fifth largest city. ASU champions intellectual and cultural diversity, and welcomes students from all 50 states and more than 100 nations across the globe. (480) 727-9386,

About Banner Alzheimer's Institute

Banner Alzheimer's Institute (BAI) is a treatment and research facility dedicated to helping patients with memory and thinking problems. It offers clinical care for patients; provides education, referral and support services for families and caregivers; and conducts leading-edge brain-imaging, clinical trials, brain imaging and genetics studies. The Institute is devoted to finding effective Alzheimer's disease-slowing and prevention treatments in the shortest time possible. BAI is owned and operated by Phoenix-based Banner Health, a nonprofit organization. For more information visit

About Barrow Neurological Institute

Barrow Neurological Institute of St. Joseph's Hospital and MedicalCenter in Phoenix, Arizona, is internationally recognized as a leader in neurological research and patient care.

Established in 1962 under the auspices of Dr. John Green, Barrow has been brought into the twenty-first century under the guiding influence of Dr. Robert Spetzler.

Barrow treats patients with a wide range of neurological conditions, including brain and spinal tumors, cerebrovascular conditions, and neuromuscular disorders. Barrow's clinicians and researchers are devoted to providing excellent patient care and finding better ways to treat neurological disorders.

About Sun Health Research Institute

For 23 years, Sun Health Research Institute, part of nonprofit Banner Health, has been a leader nationally and internationally in the effort to find answers to disorders of aging including Alzheimer's disease, Parkinson's disease,arthritis and prostate cancer. The institute, together with its Arizona Alzheimer's Consortium partners, has been designated by the National Institutes of Health as one of just 31 Alzheimer's Disease Centers in the nation. The institute's CleoRobertsCenter for Clinical Research takes laboratory discoveries to clinical trials that foster hope for new treatments. Banner Health is Arizona's leading health care provider and second largest private employer. For more information, visit

About TGen

The Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process.

About University of Arizona

The University of Arizona is one of the nation's leading public universities, with a long history of academic excellence, research innovation and a student-centered approach. A member of the prestigious Association of American Universities, the UA is ranked 13th among public universities by the National Science Foundation with total research expenditures last year of $530 million. With more than 38,000 students across three campuses representing 50 states and 124 nations, the UA is on the forefront of discoveries -- from the depths of space to the medical and genetic mysteries of life, from emerging trends in climate change to the broad complexities of the human condition. For more information, visit

About Arizona Alzheimer's Consortium

The Arizona Alzheimer's Consortium (AAC) capitalizes on the complementary resources of its seven member institutions to promote the scientific understanding and early detection of Alzheimer's disease and find effective disease-stopping and prevention therapies. Established in 1998, the Consortium also seeks to educate Arizona's residents about Alzheimer's disease, research progress in the state and the resources needed to help patients, families, and professionals manage the disease. The AAC is comprised of both the NIA-funded Arizona Disease Core Center (ADCC) and the state-funded Arizona Alzheimer's Research Center (AARC). The AAC's member research institutions include Arizona State University, the Banner Alzheimer's Institute, the Barrow Neurological Institute, Mayo Clinic Arizona, Sun Health Research Institute, the Translational Genomics Research Institute (TGen) and the University of Arizona.

About National Institute of Aging

The NIA leads the federal government effort conducting and supporting research on the biomedical, social and behavioral issues of older people. For more information on aging-related research and the NIA, go to The NIA provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer's Disease Education and Referral (ADEAR) Center site at

SOURCE Mayo Clinic
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