By Barbara A. Phillips, MD, MSPH
Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington
Dr. Phillips reports no financial relationships relevant to this field of study.
: Older people with sleep apnea had onset of cognitive decline at an earlier age than those without sleep apnea, and there was a tendency for those who used continuous positive airway pressure to have delayed onset of decline compared with those who did not.
: Osorio RS, et al. Sleep-disordered breathing advances cognitive decline in the elderly. Neurology 2015;84:1964-1971.
This report is the result of a secondary analysis of longitudinal Alzheimer’s Disease Neuroimaging Initiative (ADNI), a study designed to test whether serial MRI, PET, other biomarkers, and clinical and neuropsychological assessment can measure the progression of mild cognitive impairment and early Alzheimer’s disease. For purposes of this report, the authors queried the ADNI database for patients with self-reported sleep apnea and/or treatment with continuous positive airway pressure (CPAP) and information on age at onset of mild cognitive impairment or early Alzheimer’s disease. Data were analyzed with three different criteria for exclusion: first, by only excluding participants with missing data; second, by excluding participants with ambiguous classification of dementia onset or sleep apnea diagnosis; and third, by including only participants with incident mild cognitive impairment or Alzheimer’s disease with mild cognitive impairment as documented by clinical assessment during the follow-up period.
For the first and most inclusive analysis, 63 participants were normal and diagnosed with mild cognitive impairment at follow-up (2-3 years later), 441 participants were normal and did not develop mild cognitive impairment, 40 participants had mild cognitive impairment and were diagnosed as normal at follow-up, 217 participants had mild cognitive impairment with a reported age at onset, and 6 participants had Alzheimer’s dementia with a reported age at onset. Patients with sleep apnea were significantly younger at mild cognitive impairment onset than those without for all three analyses. In the most stringent analysis, the age difference for onset of mild cognitive impairment was 77 vs 90 years, (P < 0.01). There was not much difference in these findings when controlling for APOε4, sex, education, depression, cardiovascular disease, hypertension, diabetes, age at baseline visit, and body mass index.
As an exploratory analysis, these authors also compared the small number of participants with sleep apnea on CPAP with those with untreated sleep apnea. In the more inclusive analyses, patients with obstructive sleep apnea (OSA) who were not treated with CPAP had a significantly younger age at mild cognitive impairment onset than those who used CPAP, but this difference was not statistically significant in the most stringent analysis, perhaps because of the small sample size (10 on CPAP and 18 with OSA not treated). In this study, there was no association with Alzheimer’s dementia and age of cognitive impairment onset, regardless of sleep apnea diagnosis or treatment.
COMMENTARY
Before we rush out and start everybody on CPAP to prevent dementia, let’s take a look at some of the problems with this study. First, since we can’t randomize people to dementia or not, this report doesn’t prove causality. (The title is a bit over-reaching. It might more accurately say, “Sleep-disordered breathing is associated with earlier cognitive decline in the elderly.” And, although it’s unlikely, another possible interpretation of these findings is that cognitive decline causes sleep apnea.) Second, both dementia onset and sleep apnea diagnosis were based on self-report, except in the most stringent analyses, and even then, sleep apnea diagnosis was self-reported. Similarly, CPAP use/adherence was also self-reported. Thus, the reported findings could be due to any number of alternative possible explanations, including that people who get a diagnosis of OSA (and who use CPAP) may take better care of themselves in general (e.g., exercise more, smoke less) than those who don’t seek medical care.
But the findings are thought-provoking and potentially important, and they build on previous work. Several prior studies have shown an association between sleepiness and cognitive decline/dementia,2-5 and one report has linked objectively diagnosed sleep apnea with a higher risk of developing cognitive impairment among community-living women with sleep apnea.6 Further, the authors’ own work has demonstrated an association between sleep apnea and cerebrospinal fluid Alzheimer’s disease biomarker changes.7
What is most exciting about this paper is that it is the first study to give a signal that CPAP treatment for OSA may be associated with later onset of cognitive decline. Although the current study did not find a relationship between sleep apnea, CPAP treatment, and Alzheimer’s disease specifically, previous work has shown that patients with Alzheimer’s disease dementia have significantly slower cognitive decline over a 3-year follow-up period when treated for sleep apnea.8
What does this mean for our older patients who are considering evaluation or treatment for sleep apnea? At this stage of the game, it would be inappropriate to state definitively that CPAP treatment will delay the onset of cognitive decline or dementia. However, there is growing evidence that sleepiness (from any cause) and sleep apnea are associated with earlier onset of cognitive decline, and a suggestion that CPAP treatment may delay this occurrence. And that’s good news.
REFERENCES
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Alzheimer’s Disease Neuroimaging Intiative. Available at: http://adni.loni.usc.edu/. Accessed June 12, 2015.
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Jaussent I, et al. Excessive sleepiness is predictive of cognitive decline in the elderly. Sleep 2012;35:1201-1207.
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Foley D, et al. Daytime sleepiness is associated with 3-year incident dementia and cognitive decline in older Japanese-American men. J Am Geriatr Soc 2001;49:1628-1632.
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Elwood PC, et al. Sleep disturbance and daytime sleepiness predict vascular dementia. J Epidemiol Community Health 2011;65:820-824.
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Keage HA, et al. What sleep characteristics predict cognitive decline in the elderly? Sleep Med 2012;13:886-892.
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Yaffe K, et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA 2011;306:613-619.
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Osorio RS, et al. The interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer’s disease in cognitively normal elderly individuals. Neurobiol Aging 2013;35:1318-1324.
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Troussiere AC, et al. Treatment of sleep apnea syndrome decreases cognitive decline in patients with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2014;85:1405–1408.
