Sleep-Disordered Breathing Linked to Cognitive Impairment

Megan Brooks

August 09, 2011

August 9, 2011 — Sleep-disordered breathing is associated with a significantly increased risk for mild cognitive impairment (MCI) and dementia in elderly women, results of a prospective study indicate.

Kristine Yaffe, MD

The relationship seems to be related primarily to measures of hypoxia rather than sleep fragmentation or sleep duration, Kristine Yaffe, MD, of University of California, San Francisco and colleagues note in the August 10 issue of the Journal of the American Medical Association.

"Our findings suggest a potential role for supplemental oxygen therapy for sleep-disordered breathing in elderly individuals," the study authors conclude. "However, its role requires critical evaluation in intervention studies."

Luigi Ferini-Strambi, MD, director of the Sleep Disorders Center at the Universita Vita-Salute San Raffaele in Milan, Italy, and coauthor of an accompanying editorial, agrees.

"This study suggests that the treatment of obstructive-sleep apnea (OSA) in elderly may be a prevention strategy for MCI and dementia," he told Medscape Medical News.

In their study, Dr. Yaffe's team points out that some evidence indicates that treating patients with Alzheimer's disease and sleep-disordered breathing with continuous positive air pressure (CPAP) may slow, or even improve, cognitive impairment.

Dr. Ferini-Strambi also believes that long-term studies evaluating the role of CPAP in the prevention of cognitive dysfunction "should be performed."

In the meantime, he said, "clinical management of MCI should consider the possible implications of OSA."

"Physicians of patients with MCI and sleep-disordered breathing for whom treatment with CPAP may be indicated should consider these results, and future guidelines to formalize the clinical management of patients with MCI should consider the implications of this study and related research," Dr. Ferini-Strambi and coauthor Nicola Canessa, PhD, from the Center for Cognitive Neuroscience, Milan, Italy, conclude in their editorial.

Prospective Data Clarify Link

Most prior studies that have linked cognitive impairment to sleep-disordered breathing have been cross-sectional in design or have relied on nonobjective measures of sleep-disordered breathing, limiting the conclusions that can be drawn, the study authors note. It remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults.

Dr. Yaffe's team set out to determine the prospective relationship between sleep-disordered breathing and MCI and dementia. Their study involved 298 women without dementia at baseline, with a mean age of 82.3 years.

Overnight in-home polysomnography, conducted between January 2002 and April 2004 as part of a substudy of the Study of Osteoporotic Fractures, provided data on hypoxia, sleep fragmentation, and sleep duration. Cognitive assessments were made approximately 5 years later via neuropsychological tests and evaluation by a panel of experts.

The study team used multivariate logistic regression to determine the independent association of sleep-disordered breathing with the risk for MCI or dementia, adjusting for age, race, body mass index, educational level, smoking status, the presence of diabetes, the presence of hypertension, medication use (antidepressants, benzodiazepines, or nonbenzodiazepine anxiolytics), and baseline cognitive scores.

Of the 298 women, 105 (35.2%) had sleep-disordered breathing — defined as an apnea-hypopnea index of 15 or more events per hour of sleep — and 193 (64.7%) did not.

During follow up, MCI developed in more women with vs without sleep-disordered breathing (44.8% [n = 47] vs 31.1% [n = 60]), yielding an adjusted odds ratio (OR) of 1.85 (95% confidence interval [CI], 1.11 - 3.08).

Hypoxia the Likely Culprit

Measures of intermittent hypoxia increased the risk for the development of MCI. An elevated oxygen desaturation index (≥ 15 events/hour) was associated with an adjusted OR of 1.71 (95% CI, 1.04 - 2.83) and spending more than 7% of sleep time in apnea or hypopnea, an adjusted OR of 2.04 (95% CI, 1.10 - 3.78).

In contrast, measures of sleep fragmentation (ie, arousal index and waking after sleep onset) or sleep duration were not associated with the risk for cognitive impairment.

This study supports prior research that "hypoxia, and not the sleep fragmentation, is the mechanism through which OSA increases risk for cognitive impairment," Dr. Ferini-Strambi commented to Medscape Medical News.

In their editorial, Drs. Ferini-Strambi and Canessa say the possible coexistence of sleep-disordered breathing should be considered in trials evaluating the effects of pharmacologic and nonpharmacologic interventions on cognitive function in patients with MCI or dementia.

Support for this study was provided by the National Institute on Aging. Dr. Yaffe is a consultant for Novartis, Inc; serves on data safety and monitoring boards for Pfizer, Medivation, and the National Institute of Mental Health; is a board member for Beeson Scientific Advisory; and has grants pending with the National Institutes of Health, the Alzheimer Association, the Department of Defense, and the American Health Assistance Foundation. A complete list of author disclosures may be found with the original article. Dr. Ferini-Strambi has disclosed being a board member of Boehringer-Ingelheim, UCB-Pharma, GlaxoSmithKline, and Sanofi-Aventis.

JAMA. 2011;306:613-619, 654-655.

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