Sleep Consolidation and Sleep Apnea, Not Sleep Stage Percentages, Associated With Cognition

Matthew Pase, PhD

A recently published longitudinal study using participants from the Sleep and Dementia Consortium showed that better sleep consolidation and the absence of obstructive sleep apnea (OSA) were associated with better global cognition. No associations were found between sleep stage percentages and cognition.

Published in JAMA Network Open, the trial featured 5946 adults (median age, 56-89 years) across 5 population-based cohorts in the US who were assessed on measures of sleep architecture and OSA derived from in-home polysomnography (PSG). These included the Atherosclerosis Risk in Communities Study (ARIC), Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), Osteoporotic Fractures in Men Study (MrOS), and the Study of Osteoporotic Fractures (SOF), all of which had consistent overnight, home-based type 2 PSG and neuropsychological assessments.

Led by Matthew Pase, PHD, associate professor of psychology, Monash University, the percentage of patients with at least mild OSA, indicated by scores of at least 5 on Apnea Hypopnea Index (AHI), ranged from 45.2% in the FHS to 63.9% in MrOS. The study was largely comprised of White individuals (91.7%), followed by Black (3.9%), and other race or ethnicity (4.3%).

In the study, sleep metrics were harmonized centrally and then distributed to participating cohorts for cohort-specific analysis using linear regression while study-level estimates were pooled in random effects meta-analyses. Several covariates were used in the study, including age, age-squared, sex, education, time between PSG and neuropsychological assessment, body mass index, antidepressant use, and sedative use. Investigators also explored effect modification by sex, apolipoprotein ε4 allele status, and excessive daytime sleepiness for the primary outcome of global cognition.

Across the several observed cohorts, results showed that higher sleep maintenance efficacy (pooled ß per 1% increase, 0.08; 95% CI, 0.03-0.14; P <.01) and lower wake after sleep onset (pooled ß per 1-min increase, ­–0.07; 95% CI, –0.13 to –0.01; P = .02) were independently associated with superior global cognition. Stage 1, 2, 3, and REM sleep were defined as the duration of each sleep stage expressed as a percentage of total sleep time. These sleep stage percentages did not factor into global cognition.

Findings also demonstrated that those with mild to severe OSA (AHI ≥5) had worse global cognitive function vs those with AHI scores of less than 5 (pooled ß, –0.06; 95% CI, –0.11 to –0.01; P = .01). Similar findings were observed for those with at least moderate OSA (AHI ≥15) vs AHI scores of less than 5 (pooled ß, –0.06; 95% CI, –0.11 to –0.01; P = .02). Notably, sleep time with oxygen saturation less than 90% was not associated with global cognitive function.

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"This study’s finding of an association between mild OSA and poorer cognition in persons who did not present to a sleep clinic is an important observation,” Pase et al wrote. "Persons with OSA diagnosed based on incidental findings compared with patients referred clinically for PSG may differ across several characteristics, including comorbidities, overall dementia risk factor burden, and the severity of sleep disturbances. Although there are direct (eg, intermittent hypoxia leading to ischemic brain injury or sleep fragmentation) and indirect (eg, systemic inflammation or cardiovascular instability) mechanisms that may link OSA with poorer cognition, no conclusions regarding causation can be made from this observational study."

According to pooled estimates, those with shorter total sleep time, considered less than 6 hours a night, had poorer attention and processing speed (pooled ß, 0.07; 95% CI, 0.02-0.11). In an exploration of interaction associations, investigators documented that the association between REM sleep percentage and global cognition differed by sex in the CHS cohort, with a positive association observed in females (ß per 1% increase, 0.02; 95% CI, –1.25 to 1.48; P = .01) and no association observed in men (ß per 1% increase, –0.01; 95% CI, –1.66 to 1.54; P = .25; P for interaction =.01).

Additional data from the FHS indicated that associations between moderate to severe OSA (AHI ≥15 vs <5) and global cognition differed by excessive daytime sleepiness. OSA was associated with poorer global cognition in patients with (ß, –0.54; 95% CI, –0.96 to –0.11; P = .01) but not those without (ß = 0.16; 95% CI, –0.05 to 0.37; P =.14) excessive daytime sleepiness (P for interaction = .006).

The investigators concluded, "There was little evidence to suggest that sex, APOE ε4, or excessive daytime sleepiness interacted with associations. With respect to individual cognitive domains, only short sleep duration was associated with poorer attention and processing speed. Future Sleep and Dementia Consortium analyses will build upon these findings to further investigate whether and how poor sleep may be associated with cognitive impairment and dementia."

REFERENCES
1. Pase MP, Harrison S, Misialek JR, et al. Sleep architecture, obstructive sleep apnea, and cognitive function in adults. JAMA Netw Open. 2023;6(7):e2325152. doi:10.1001/jamanetworkopen.2023.25152.