Among older women, sleep disordered breathing was associated with an increased risk of developing cognitive impairment 5-years later. In addition, even after adjusting for demographic risk factors and comorbidities, we found that 2 of 3 indices of hypoxia, but not sleep fragmentation or duration, were associated with incident MCI or dementia, suggesting that hypoxia is a likely mechanism through which sleep disordered breathing increases risk for cognitive impairment.
Prior cross-sectional studies of sleep disordered breathing and cognitive function in elderly populations have reported conflicting results; some investigations have reported associations of sleep disordered breathing with either lower cognitive test scores or dementia6-8
while others have not.26, 27
Such divergent findings could be due to the differences in measurement and definition of sleep disordered breathing or of cognitive impairment. These earlier cross-sectional studies are also limited in establishing the causal pathway of this association. Our investigation is the first, to our knowledge, to report on the longitudinal relationship between sleep disordered breathing and risk of MCI/dementia.
We explored possible mechanisms (hypoxia and sleep fragmentation or duration) through which sleep disordered breathing might increase the risk for cognitive impairment. Sleep itself plays a critical role in the consolidation of long-term memory which occurs during slow-wave sleep.28
While experimental studies have reported inconsistent effects of sleep fragmentation and hypoxia on deficits in neurocognitive performance,29-33
the literature does not extend to the long term effects of sleep on cognition.
In our study, none of the sleep fragmentation or duration measures had a significant association with cognitive impairment after accounting for potential confounders, while the hypoxia measures were consistently associated with MCI/dementia. 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.34
However, it is important to note that because cerebral blood flow may be affected in elderly patients35
, other mechanisms such as hypercapnia could also be involved.
In patients with Alzheimer disease, therapeutic trials of treatment with continuous positive airway pressure (CPAP) for sleep disordered breathing have been shown to slow or even improve cognitive impairment.36, 37
Furthermore, a recent investigation of individuals with sleep apnea indicated that treatment with continuous positive airway pressure not only improved cognitive scores, but also increased grey matter volume in the hippocampal and frontal regions.38
To fully evaluate the impact of treatment for sleep disordered breathing in elderly populations, additional trials with larger sample sizes, longer treatment periods, and more diverse populations are required. Of interest, our findings suggest a potential role for supplemental oxygen therapy for sleep disordered breathing in elderly individuals; however, its role requires critical evaluation in intervention studies. In addition, future studies should consider the association of sleep disordered breathing with impairment in specific cognitive domains as well as changes in these variables over time.
Both the oxygen desaturation index and percentage time in apnea or hypopnea were associated with incident cognitive impairment. The oxygen desaturation index is a measurement of intermittent hypoxemia while the time in apnea or hypopnea estimates the proportion of the sleep period during which the respiration consists of apneas and hypopneas. Unlike the apnea-hypopnea index, which is simply a count of apneas plus hypopneas per hour of sleep (can be elevated when breathing disturbances occur frequently but are of brief duration), the percentage of time in apnea or hypopnea reflects both the frequency and duration of breathing disturbances and thus may better reflect sleep-related gas exchange abnormalities than the apnea-hypopnea index.
Percentage of time in oxyhemoglobin desaturation, as measured by sleep time with oxygen saturation of less than 90% in our study, is another measure of sleep-related hypoxemia and was not significantly associated with mild cognitive impairment or dementia; however, it may not reflect the effects of intermittent hypoxemia as well as the other 2 indices of hypoxemia. Studies suggest intermittent hypoxia, rather than continuous hypoxia, is associated with greater risk of oxidative stress and adverse outcomes.39, 40
Although our prospective design with objective measures of sleep disordered breathing and rigorous methods to diagnose cognitive impairment supports the hypothesis that sleep disordered breathing precedes dementia, there are several limitations that warrant consideration. While measurement of polysomnography data in a sleep laboratory over multiple nights is the criterion standard, several studies indicate that polysomnography measures in the home vs in the lab taken during 1 night vs multiple nights are reliable, although misclassification bias is possible.41-43
In this study, polysomnography data was collected in the home for only 1 night so variability in sleep disturbance measures over time may not have been captured. Because the Study of Osteoporotic Fractures cohort is composed of mostly white women, these findings may not be generalizable to men or more ethnically diverse populations. Finally, because women with more severe sleep disordered breathing or cognitive impairment were less likely to survive to the eighth and ninth decades of life, there may be a survival bias in our results, but this would most likely result in an underestimate of the association.
We found that among women with a mean age of 82 years, sleep disordered breathing was associated with an increased risk of cognitive impairment. Our results indicate that this relationship seems to be related primarily to measures of hypoxia. Given the high prevalence of both sleep disordered breathing and cognitive impairment among older adults, the possibility of an association between the 2 conditions, even a modest one, has the potential for a large public health impact. Furthermore, the finding that hypoxia and not sleep fragmentation or duration seems to be associated with risk of MCI/dementia provides clues to the mechanisms through which sleep disordered breathing might promote cognitive impairment. The increased risk for cognitive impairment associated with sleep disordered breathing opens a new avenue for additional research on the risk for development of MCI/dementia and exploration of preventive strategies that target sleep quality including sleep disordered breathing.