Sleep-Disordered Breathing, Hypoxia, and Risk of Mild Cognitive Impairment and Dementia in Older Women

1. Kristine Yaffe, MD;
2. Alison M. Laffan, PhD;
3. Stephanie Litwack Harrison, MPH;
4. Susan Redline, MD, MPH;
5. Adam P. Spira, PhD;
6. Kristine E. Ensrud, MD;
7. Sonia Ancoli-Israel, PhD;
8. Katie L. Stone, PhD

[+] Author Affiliations

1. Author Affiliations: Departments of Psychiatry, Neurology, and Epidemiology, University of California, San Francisco (Dr Yaffe); San Francisco Veterans Affairs Medical Center, San Francisco, California (Dr Yaffe); San Francisco Coordinating Center, California Pacific Medical Center, San Francisco (Drs Laffan and Stone and Ms Harrison); Division of Sleep Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Dr Redline); Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Dr Spira); Departments of Medicine, Epidemiology, and Community Health, University of Minnesota, Minneapolis (Dr Ensrud); Veterans Affairs Medical Center, Minneapolis, Minnesota (Dr Ensrud); and Department of Psychiatry, University of California, San Diego (Dr Ancoli-Israel).

Abstract

Context Sleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults. Cross-sectional studies have linked sleep-disordered breathing to poor cognition; however, it remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults.

Objectives To determine the prospective relationship between sleep-disordered breathing and cognitive impairment and to investigate potential mechanisms of this association.

Design, Setting, and Participants Prospective sleep and cognition study of 298 women without dementia (mean [SD] age: 82.3 [3.2] years) who had overnight polysomnography measured between January 2002 and April 2004 in a substudy of the Study of Osteoporotic Fractures. Sleep-disordered breathing was defined as an apnea-hypopnea index of 15 or more events per hour of sleep. Multivariate logistic regression was used to determine the independent association of sleep-disordered breathing with risk of mild cognitive impairment or dementia, adjusting for age, race, body mass index, education level, smoking status, presence of diabetes, presence of hypertension, medication use (antidepressants, benzodiazepines, or nonbenzodiazepine anxiolytics), and baseline cognitive scores. Measures of hypoxia, sleep fragmentation, and sleep duration were investigated as underlying mechanisms for this relationship.

Main Outcome Measures Adjudicated cognitive status (normal, dementia, or mild cognitive impairment) based on data collected between November 2006 and September 2008.

Results Compared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% [n = 60] vs 44.8% [n = 47]; adjusted odds ratio [AOR], 1.85; 95% confidence interval [CI], 1.11-3.08). Elevated oxygen desaturation index (≥15 events/hour) and high percentage of sleep time (>7%) in apnea or hypopnea (both measures of disordered breathing) were associated with risk of developing mild cognitive impairment or dementia (AOR, 1.71 [95% CI, 1.04-2.83] and AOR, 2.04 [95% CI, 1.10-3.78], respectively). Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.

Conclusion Among older women, those with sleep-disordered breathing compared with those without sleep-disordered breathing had an increased risk of developing cognitive impairment.