Obstructive sleep apnea linked to worsening cognition in older adults
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Key takeaways:
- Sleep apnea was linked to worsening cognition over 5 years.
- Adults aged older than 75 years, men and carriers of apolipoprotein E4 showed steeper cognitive decline associated with sleep apnea.
Older adults that suffer with hypoxemia while sleeping showed decreased measures of cognition over a 5-year period, according to study results published in European Respiratory Journal.
“At the moment, sleep apnea is not officially recognized as a risk factor for cognitive decline/dementia,” Nicola Andrea Marchi, MD, PhD student at Lemanic Neuroscience Doctoral School, told Healio. “The results of our study suggest that sleep apnea — in particular, nocturnal hypoxemia associated with sleep apnea — is an independent predictor of steeper cognitive decline among older adults, thus suggesting that sleep apnea is a modifiable (because it is treatable) risk factor for cognitive decline/dementia. This study contributes to increasing awareness of the consequences of sleep apnea on brain health among clinicians and researchers working in the field of sleep medicine, pulmonology and neurology.”
Using data from a prospective cohort study, Marchi and colleagues analyzed 358 older adults (mean age, 71 years; 42.5% men) without dementia aged 65 years old or older from Switzerland to find out if obstructive sleep apnea (OSA) is linked to cognitive decline over 5 years.
To observe the relationship between these two factors, researchers assessed several polysomnographic OSA parameters of breathing/hypoxemia and sleep fragmentation in relation to changes in cognition. Several tests measured different aspects of cognition, such as the Mini-Mental State Examination for global cognitive function, the Stroop test Victoria version for processing speed and executive function, verbal fluency tasks for executive control and verbal ability, the Free and Cued Selective Reminding Test for episodic verbal memory, the 40-DO naming test for language and a constructional praxis task for visuospatial function.
Two cognitive assessments, one at baseline and one after 5 years, were performed.
Further, researchers evaluated the associations across three models, with each model including more adjustments for potential confounding variables. For example, the first model adjusted for age, sex, high school education and apolipoprotein E4 (ApoE4), and all these factors were adjusted for in the second model along with BMI, diabetes, hypertension, smoking, alcohol consumption and psychotropic drugs. Lastly, the third model adjusted for all the above variables plus depression, Epworth Sleepiness Scale score, continuous positive airway pressure (CPAP) and COPD.
Main findings
Of the total cohort, 270 older adults had an average peripheral oxygen saturation of more than 92.5% during sleep, whereas 88 individuals had an average of less than or equal to 92.5%, signaling poor oxygenation.
Over the mean follow-up period of 5.2 years, researchers observed “steeper declines” in cognition in those with poorer mean peripheral oxygen saturation levels while sleeping compared with those with oxygen saturation above 92.5%. After adjusting for all possible confounding variables, these adults showed cognitive decline in the Mini-Mental State Examination with an annual change of –0.12 (P = .004), Stroop test condition one with an annual change of 0.53 (P = .002) and the Free and Cued Selective Reminding Test delayed free recall task with an annual change of –0.05 for 1% decrease (P = .008).
A drop in cognition assessed in the Stroop test condition one task was further linked to an extended duration of sleep with mean peripheral oxygen saturation less than 90% (annual change, 0.47; P = .006), according to researchers.
Greater odds for a significant cognitive decline (defined by a decline > 1 standard deviation compared with the mean cognitive change) with lower mean peripheral oxygen saturation levels were found in two cognition assessments. Over the follow-up period and following adjustment for all variables, researchers observed that adults with poor oxygen saturation levels had two or more fewer points on the Mini-Mental State Examination (OR = 3.27; P = .001) and needed greater than or equal to 7.3 seconds more to finish the Stroop test condition one task (OR = 4.64; P = .007).
Researchers also found a significant relationship between lower mean oxygen saturation as a continuous variable and poorer scores in the delayed free recall task after adjusting for model one variables (OR for 1% decrease = 1.21; P = .007); this relationship was not significant in models two or three.
“Results in the entire sample were reasonably expected in terms of the sleep apnea variables associated with the cognitive decline (ie, the variables of nocturnal hypoxemia, but not variables of sleep fragmentation) and the pattern of cognitive decline, which was characterized by a decline in global cognition, processing speed and executive function, suggests a dysfunction of the frontal lobe,” Marchi told Healio.
Moderation analysis
When evaluating subgroups of the study population, researchers found that adults aged older than 75 years showed greater decreases in processing speed with more severe sleep apnea (apnea-hypoxemia index of 15 events/hour).
Further, a higher severity of sleep apnea was linked to less phonemic fluency in men (unstandardized B-coefficient [B] = –0.7; P = .003) and less global cognitive function in those who carried ApoE4 (B = –0.21; P = .007). These demographics were also observed when evaluating the relationship between oxygen desaturation index 15 events/hour and declines in phonemic fluency (men, B = –0.71; P = .002) or global cognitive function (ApoE4 carriers, B = –0.21; P = .009).
“A greater decline in the older participants and men was a bit unexpected,” Marchi told Healio. “On the other hand, a greater cognitive decline in ApoE4 carriers was expected because the ApoE4 allele is known to increase the risk of dementia.”
Further studies are needed to determine what patient demographics and sleep apnea measures can predict a reduction in cognition, Marchi said.
“Sleep apnea is a very common condition and probably not all patients with sleep apnea have the same risk of cognitive decline,” he told Healio. “It is more likely that there is a subgroup of patients with a higher risk of sleep apnea-related cognitive decline. Future studies need to further investigate the patient's characteristics (age, sex, genetic background, comorbidities, etc) and the specific markers of sleep apnea that are the most relevant to predict cognitive decline.”
“Given that sleep apnea is a treatable condition, it may represent a modifiable risk factor for dementia,” Marchi added. “The primary treatment for sleep apnea is CPAP. Now, the largest randomized controlled trials that have investigated the effect of CPAP on cognitive functioning have yielded null results or have shown a limited beneficial effect of CPAP. These inconclusive results may be because these studies did not target the subgroup of sleep apnea patients with the higher risk of cognitive decline. Therefore, after understanding the specific patient and sleep apnea characteristics that increase the risk of cognitive decline/dementia, future randomized controlled trials could test the effect of CPAP on cognitive decline among this specific subgroup of patients.”
For more information:
Nicola Andrea Marchi, MD, can be reached at nicola.marchi@unil.ch.