Sleep apnea linked to cognitive impairment in older women

By Steve Tokar

Older women with sleep-disordered breathing (SDB)—the restriction or interruption of breathing during sleep—are more likely to show cognitive impairment than women without SDB, according to a study led by researchers at the San Francisco VA Medical Center and University of California, San Francisco.

The association is even stronger in women with at least one copy of the APOE e4 gene, which is considered a risk factor for Alzheimer’s disease as well as SDB.

The study is published in the January 2008 issue of the Journal of the American Geriatrics Society.

SDB includes apnea—temporary cessation of breathing—as well as hypopnea, which is “a significant reduction in breathing,” according to lead author Adam P. Spira, PhD, a geriatrics researcher at SFVAMC.

Using standard cognitive tests, the researchers measured the cognitive abilities of 448 women with a mean age of 82.8 years. The women were subjects in the Study of Osteoporotic Fractures, an ongoing multi-center study of women 65 and older funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

They then collected one night’s worth of sleep data on the women using polysomnography, “a method of measuring multiple domains of sleep-related physiologic responses,” explains Spira, who is also a geriatrics fellow at UCSF. “We looked at heart rate, respiration, brain waves, blood oxygen, snoring, and many other measures to get a true picture of breathing patterns during sleep.”

The greater the severity of apnea or hypopnea in a study subject, the greater the likelihood the subject tested as cognitively impaired.

Genetic testing was then done on blood samples from 242 of the women at two of the study centers. Within that group, the association between apnea/hypopnea severity and cognitive impairment was substantially greater among women with at least one copy of the e4 variant of the APOE gene than in women without the e4 variant. 

Spira stresses that the study does not demonstrate a cause-and-effect relationship between SDB and cognitive impairment, but simply an association. He notes that even if there is a cause-and-effect relationship, the exact mechanism by which SDB might contribute to cognitive impairment is unknown. “However, low blood oxygen that might be associated with cessations or reductions in respiration could lead to neuronal damage,” he says.

“The significance of this finding is that SDB is treatable,” says senior author Kristine Yaffe, MD, chief of geriatric psychiatry at SFVAMC and professor of psychiatry, neurology, and epidemiology at UCSF. “If we treat it effectively, we might be able to prevent cognitive impairment in some older adults. This is especially important for those with the APOE e4 gene, who may be even more vulnerable to the possible neurological effects of SDB.”

All of the women in the study lived at home, which is significant, according to Spira. “Previous studies had indicated a link between ADB and cognitive impairment, but the study subjects were either Alzheimer’s patients or living in nursing homes,” he says. “We wanted to know if this association exists in the general population of older community-dwelling adults.”

Spira cautions that the study is a “snapshot,” consisting of one cognitive test and one night’s worth of sleep pattern data. “We did not observe these women over time to see if there was a change in their cognition,” he says. “We hope to do that in future research.”

He also says the phenomenon needs to be explored in men.

Coauthors of the study are Terri Blackwell, MA, and Katie L. Stone, PhD, of the California Pacific Medical Center Research Institute, San Francisco Calif.; Susan Redline, MD, of Case Western Reserve University, Cleveland, Ohio; Jane A. Cauley, DrPH, of the University of Pittsburgh, Pittsburgh, Penn.; and Sonia Ancoli-Israel, PhD, of the University of California, San Diego and Veterans Affairs San Diego Healthcare System.

The study was supported by grants from the National Institutes of Health, some of which were administered by the Northern California Institute for Research and Education.

NCIRE—the Veterans Health Research Institute—is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.