Sleep apnea linked to cognitive decline

Older women with sleep-disordered breathing are more likely to develop cognitive impairment than those who do not have the condition, data indicate.

Women who experienced 15 or more apnea or hypopnea events per hour of sleep had higher rates of mild cognitive impairment and dementia after five years than those without (44.8% versus 31.1%; P=0.02), Kristine Yaffe, MD, of the University of California San Francisco, and colleagues, reported in the Journal of the American Medical Association.

The association between sleep-disordered breathing and higher rates of cognitive impairment remained (OR=2.36; 95% CI:1.34-4.13), even after adjusting for potential confounding factors including age, race, BMI, education level, smoking status, diabetes, hypertension, medication use and baseline cognitive scores.

"Given the high prevalence of both sleep-disordered breathing and cognitive impairment among older adults, the possibility of an association between the two conditions, even a modest one, has the potential for a large public health impact," the researchers wrote.

If the findings hold up in further studies, sleep apnea therapies such as continuous positive airway pressure (CPAP) may have potential to slow cognitive decline and dementia, the researchers suggested.

Although data from previous studies have linked sleep disordered breathing and cognitive impairment, it was unclear which problem preceded the other. To determine this, as well as the potential mechanisms governing the association, the researchers evaluated data from 298 older women (mean age 82 years) free from dementia, who participated in a sleep and cognition substudy of the Study of Osteoporotic Fractures.

At baseline about one-third of the patients (35.2%) had sleep-disordered breathing determined by overnight polysomnography performed in their homes. During the median 4.7-year follow-up period, 20.1% developed mild cognitive impairment and 15.8% developed dementia.

Sleep fragmentation and duration were not related to the odds of developing cognitive impairment, the researchers found. However, two measure of hypopoxia — elevated oxygen desaturation index (OR= 1.98) and a high percentage of sleep time in apnea or hyponea (OR= 2.32) — were positively associated.

“This suggests that hypoxia is a likely mechanism for this relationship, which is supported by recent animal models of chronic hypoxia that demonstrated similar impairments in cognition with possible implications for apolipoprotein E, inflammatory and regulatory pathways,” the researchers wrote.

Other mechanisms, such as hypercapnia, may also play a role, the researchers noted, as many elderly patients may experience changes in cerebral blood flow.

Study limitations include possible misclassification of sleep-disordered breathing status due to only one night of polysomnography data, a study population composed mostly of white women and potential survival bias, the researchers acknowledged. They called for more sties with “larger sample sizes, longer treatment periods, and more diverse populations.”

In an accompanying editorial, Nicola Canessa, PhD, and Luigi Ferini-Strambi, MD, of Vita-Salute San Raffaele University in Milan, suggested that large, clinical trials be conducted to explore CPAP in elderly participants with sleep-disordered breathing.

"Moreover, in trials evaluating the effects of pharmacological and nonpharmacological ... interventions on cognitive function in patients with mild cognitive impairment or dementia, the possible coexistence of sleep-disordered breathing should be considered," they wrote.

Yaffe K, et al  JAMA. 2011; 306: 613-619.

Canessa N, Ferini-Strambi L. JAMA 2011; 306: 654-655.

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