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Stanford Report, October 3, 2001

Link between sleep apnea, Alzheimer's disease under study

By MIKE GOODKIND

Researchers at Stanford University Medical Center are working to make sense of a peculiar link between a common sleep disorder and Alzheimer's disease. They hope their efforts will alleviate one of the most socially and personally devastating results of Alzheimer's.

"Sleep disorders are the No. 1 reason Alzheimer's patients are institutionalized. Most people can live with a loved one who is a little forgetful, but when the loved one is up all night and agitated, most people feel it's time to take action to save the family," said Jerome Yesavage, MD, professor of psychiatry and behavioral sciences and director of the National Institute of Aging Alzheimer's Disease Center at the Veterans Affairs Palo Alto Health Care System.

A strong genetic connection between Alzheimer's and sleep apnea was reported June 13 in the Journal of the American Medical Association by Emmanuel Mignot, MD, PhD, director of the Center for Narcolepsy at Stanford's Center for Human Sleep Research, and Greer Murphy, MD, PhD, director of the Neurochemistry/Genetics Core of the Stanford Alzheimer's Disease Center. Their research showed that a particular gene linked to sleep apnea also predisposes carriers to the development of Alzheimer's and heart disease.

Yesavage said his interdisciplinary center received $3.9 million in federal funds from the National Institute of Aging for five years starting in October 2000. The center is a "more focused continuation" of his Aging Clinical Research Center, also funded by the NIA, at the VA Palo Alto facility. The grant is based at the VA Palo Alto facility.

"Alzheimer's is a tremendously complex disease with both physical and social consequences that need to be studied and remedied," said Yesavage. Despite progress in recent years, "much remains to be understood, especially in terms of preventive mechanisms, the disease's impact on caregivers -- including the varied needs of those from many ethnic and cultural backgrounds -- and ways to improve sleep and reduce behavioral complications."

Murphy, who co-authored the study on the sleep apnea gene connection and is a collaborator at both the sleep and Alzheimer's centers, said the interdisciplinary effort has been integral to progress made thus far, including the development of effective and promising medications to treat symptoms. These and other new medications may eventually be used to treat the underlying mechanisms of Alzheimer's, which results in forgetfulness and associated symptoms including erratic behavior, Murphy said.

"Because of the centers, we were able to pull together the money needed to follow a large number of patients, collect the bank of DNA samples we needed and draw from a large group of older patients -- some with Alzheimer's, some without," he said. The centers also provided the technical infrastructure required.

Murphy said the use of mice implanted with a gene associated with human Alzheimer's was particularly valuable "because we can study the life cycle of the disease in [genetically altered or transgenic] mice much more quickly and in greater laboratory depth than with people." If nothing else, he said, "the mice in 12 months develop symptoms that require 60 years to develop in humans."

Yesavage said a key aspect of the NIA center is to award pilot grants to encourage investigators at Stanford to consider new projects in Alzheimer's research, as well as to encourage seasoned Alzheimer's disease investigators to try novel approaches.

He said unique resources of the center include a newly formed Stanford Brain Bank, which will help researchers obtain, dissect and process brain material from donors in a timely fashion after death. Neuropathological work is led by Dikran Horoupian, MBBCH, professor of pathology (emeritus), and research associate Ahmad Salehi, MD, PhD.

Yesavage said the center also has a mutually beneficial relationship with Jared R. Tinklenberg, MD, professor of psychiatry, who directs a state-sponsored Alzheimer's disease center at the VA Palo Alto facility.

Other current collaborators include a neuroscience group headed by William Mobley, MD, professor and chair of neurology; Eric Shooter, PhD, professor of neurobiology; and Murphy. Dolores Gallagher-Thompson, PhD, associate professor (research) of psychiatry and behavioral sciences, will conduct studies of caregivers of Alzheimer's disease patients, while methodology and biostatistical leadership is provided by Helena Kraemer, professor of biostatistics in psychiatry.