Sleep-Disordered Breathing May Speed Cognitive Decline

Pauline Anderson

April 15, 2015

Sleep-disordered breathing (SDB) accelerates cognitive decline — in some cases by almost 10 years — and treating this condition may delay this decline, a new study suggests.

Researchers found that older patients who snored or had episodes of complete airway obstruction during sleep had an earlier age of cognitive decline than patients without these conditions but that progression of cognitive impairment was delayed in those using continuous positive airway pressure (CPAP) to treat the sleep problem.

There's evidence that SDB is "very prevalent" in the elderly, could be a risk factor for Alzheimer's disease (AD), but is underdiagnosed in this population, said lead author Ricardo Osorio, MD, research assistant professor of psychiatry, NYU Center for Brain Health, New York. "There's a lack of awareness about it both in the medical community and among patients."

If patients have cognitive or sleep complaints, "sleep disordered breathing is definitely something that doctors should try to rule out or at least see if it's present," said Dr Osorio told Medscape Medical News.

The study was published online April 15 in Neurology.

More Stringent Criteria

Community-dwelling elderly participants in the longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) were included in the study. The primary goal of ADNI is to test whether serial MRI, positron emission tomography, other biomarkers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early AD dementia.

Researchers performed analyses on three subsets of participants, each progressively more stringent in terms of inclusion criteria. The first subset, for example, included patients (or their informants) who reported age at onset of their memory decline, while the third subset included only those with clinically documented age at onset of MCI or AD dementia.

Including the more stringent criteria category addressed the issue of recall bias because that approach entailed a "more objective measurement of decline," commented Dr Osorio.

The study showed that patients with SDB in all three study subsets had a significantly younger age at MCI onset than those without SDB. For the first subset, the ages were 72.63 vs 83.67 years; for the second subset, they were 72.15 vs 83.45 years; and for the third subset, they were 77.40 vs 89.89 years (all P < .01).

The significance of between-group differences did not change after controlling for APOE ε4 genetic status, sex, education, body mass index, depression, cardiovascular disease, hypertension, diabetes, and age at baseline.

As for AD dementia, only patients with SDB in the most stringent group had a significantly younger age at onset. In this third subset, the age at AD dementia onset was 83.46 years in patients with SDB compared with 88.13 years in those without SDB (P < .05). After adjustment for confounders, the effect in this group became a trend.

Although in the other two subsets the difference was not significant, there was a trend toward younger ages of decline in those with SDB.

Lack of significance could have occurred because recall bias is a confounder or because it's difficult to determine whether sleep disturbances cause dementia or dementia causes sleep disturbances," said Dr Osorio. "It's hard to see a causal link between sleep and dementia because AD in itself impacts sleep."

How might SDB lead to an earlier onset of cognitive decline? According to Dr Osorio, episodes of intermittent hypoxia during sleep could be a risk factor. Hypoxia may interfere with sleep architecture and the cycling between REM (rapid eye movement) and non-REM sleep stages, he said.

Patients with SDB who were not treated with CPAP had a younger age at MCI onset than patients with SDB receiving CPAP. In the first subgroup, the ages at onset were 72.63 vs 82.10 years; and in the second group, the ages were 72.11 vs 82.10 years (both P < .01).

Although in the third subset the difference wasn't significant, there was a trend toward younger age of decline in treated vs untreated SDB. The lack of significance could be due to small sample size, said Dr Osorio.

The study did not show any significant effect of CPAP on the age at onset of AD in any of the subsets. Dr Osorio pointed out that there were only 35 patients with AD using CPAP in the most inclusive subset. Another issue was compliance, about which researchers in this study had no information.

"At least 50% of people who are prescribed CPAP don't use it or use it less than 4 hours per night," said Dr Osorio. "We also didn't have information on whether they were using it properly or not."

However, he added, some studies have found an effect of CPAP on delaying dementia. "There is some evidence in the literature that CPAP might benefit this group, but we were unable to show that effect."

The small number of patients who were using other treatments for SDB — eg, dental appliances or surgery — were excluded from the analysis.

Dr Osorio and his research colleagues will carry out a separate non-ADNI study that uses spinal fluid biomarkers to look at the effect of CPAP on initially cognitively normal patients with SDB aged 60 to 85 years.

SDB affects 52.6% of elderly men and 26.3% of elderly women.

Further Investigation of CPAP

Invited to comment, sleep expert Judy Willis, MD, a neurologist in Santa Barbara, California, and member of the American Academy of Neurology (AAN), said the new study adds "significant support" to the "less specific suggestions" of a link between SDB and earlier age of cognitive decline that were found in previous research.

Dr Willis noted that using three study subsets defined by progressively stringent criteria strengthens the study conclusions "and continues to raise the bar for connecting outcome with the variable studied, especially separate analyses for each subset of age of onset of MCI or AD dementia."

The study also "uniquely considered" CPAP in delaying cognitive decline, said Dr Willis. "Although there is not yet full correlation, this study supports the value of further investigation regarding CPAP as a potential intervention for delaying age at MCI decline onset in appropriate patients."

That CPAP might delay cognitive decline will strengthen her argument for recommending this intervention to patients with SDB, said Dr Willis.

"Such treatment is an important consideration for all patients with sleep-disordered breathing who fall into the guidelines for treatment with CPAP, but this study increases both my ability to promote patients to follow this treatment suggestion and adds to the importance of insurers to support the medical value of this intervention."

The study was supported by the Alzheimer's Disease Neuroimaging Initiative; the National Institute of Health's National Heart, Lung, and Blood Institute; the Foundation for Research in Sleep Disorders; and James B. Kuhn. Dr Osorio has disclosed no relevant financial relationships.

Neurology. Published online April 15, 2015. Abstract

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