Associations of baseline obstructive sleep apnea and sleep macroarchitecture with cognitive function after 8 years in middle-aged and older men from a community-based cohort study.

Previous prospective studies examining associations of obstructive sleep apnea and sleep macroarchitecture with future cognitive function recruited older participants, many demonstrating baseline cognitive impairment. This study examined obstructive sleep apnea and sleep macroarchitecture predictors of visual attention, processing speed, and executive function after 8 years among younger community-dwelling men. Florey Adelaide Male Ageing Study participants (n = 477) underwent home-based polysomnography, with 157 completing Trail-Making Tests A and B and the Mini-Mental State Examination. Associations of obstructive sleep apnea (apnea-hypopnea index, oxygen desaturation index, and hypoxic burden index) and sleep macroarchitecture (sleep stage percentages and total sleep time) parameters with future cognitive function were examined using regression models adjusted for baseline demographic, biomedical, and behavioural factors, and cognitive task performance. The mean (standard deviation) age of the men at baseline was 58.9 (8.9) years, with severe obstructive sleep apnea (apnea-hypopnea index ≥30 events/h) in 9.6%. The median (interquartile range) follow-up was 8.3 (7.9-8.6) years. A minority of men (14.6%) were cognitively impaired at baseline (Mini-Mental State Examination score <28/30). A higher percentage of light sleep was associated with better Trail-Making Test A performance (B = -0.04, 95% confidence interval [CI] -0.06, -0.01; p = 0.003), whereas higher mean oxygen saturation was associated with worse performance (B = 0.11, 95% CI 0.02, 0.19; p = 0.012). While obstructive sleep apnea and sleep macroarchitecture might predict cognitive decline, future studies should consider arousal events and non-routine hypoxaemia measures, which may show associations with cognitive decline.

Sleep macroarchitecture but not obstructive sleep apnea is independently associated with cognitive function in only older men of a population-based cohort.

Evidence linking obstructive sleep apnea with cognitive dysfunction predominantly comes from clinical or select community samples. We investigated the independent cross-sectional association of obstructive sleep apnea and sleep macroarchitecture parameters with cognitive function in unselected community-dwelling middle-aged and older men. Four hundred and seventy-seven Florey Adelaide Male Ageing Study participants underwent successful home-based polysomnography. They also completed cognitive testing, including the inspection time task, Fuld object memory evaluation, trail-making test A and B, and mini-mental state examination. Multivariable regression models examined independent cross-sectional associations of obstructive sleep apnea and sleep macroarchitecture parameters with cognitive function. In univariable analyses, a higher apnea-hypopnea index and percentage of total sleep time with oxygen saturation <90% were associated with worse trail-making test A performance (both p < .05). A higher apnea-hypopnea index was also associated with worse trail-making test B performance and slower inspection time (both p < .05). In adjusted analyses, obstructive sleep apnea and sleep macroarchitecture parameters were not associated with cognitive function (all p > .05). In age-stratified analysis in men ≥65 years, greater stage 1 sleep was independently associated with worse trail-making test A performance, whereas greater stage 3 sleep was independently associated with better trail-making test A performance (both p < .05). Our findings suggest that obstructive sleep apnea is not independently associated with cognitive function. In older, but not younger, men, light sleep was associated with worse attention, whereas deep sleep was associated with better attention. Longitudinal population-based cohort studies are needed to determine if obstructive sleep apnea and disrupted sleep macroarchitecture independently predict prospective cognitive dysfunction and decline.

The association between sleep spindles and cognitive function in middle-aged and older men from a community-based cohort study.

OBJECTIVES: Previous studies examining associations between sleep spindles and cognitive function attempted to account for obstructive sleep apnea without consideration for potential moderating effects. To elucidate associations between sleep spindles, cognitive function, and obstructive sleep apnea, this study of community-dwelling men examined cross-sectional associations between sleep spindle metrics and daytime cognitive function outcomes following adjustment for obstructive sleep apnea and potential obstructive sleep apnea moderating effects. METHODS: Florey Adelaide Male Ageing Study participants (n = 477, 41-87 years) reporting no previous obstructive sleep apnea diagnosis underwent home-based polysomnography (2010-2011). Cognitive testing (2007-2010) included the inspection time task (processing speed), trail-making tests A (TMT-A) (visual attention) and B (trail-making test-B) (executive function), and Fuld object memory evaluation (episodic memory). Frontal spindle metrics (F4-M1) included occurrence (count), average frequency (Hz), amplitude (µV), and overall (11-16 Hz), slow (11-13 Hz), and fast (13-16 Hz) spindle density (number/minute during N2 and N3 sleep). RESULTS: In fully adjusted linear regression models, lower N2 sleep spindle occurrence was associated with longer inspection times (milliseconds) (B = -0.43, 95% confidence interval [-0.74, -0.12], p = .006), whereas higher N3 sleep fast spindle density was associated with worse TMT-B performance (seconds) (B = 18.4, 95% confidence interval [1.62, 35.2], p = .032). Effect moderator analysis revealed that in men with severe obstructive sleep apnea (apnea-hypopnea index ≥30/hour), slower N2 sleep spindle frequency was associated with worse TMT-A performance (χ2 = 12.5, p = .006). CONCLUSIONS: Specific sleep spindle metrics were associated with cognitive function, and obstructive sleep apnea severity moderated these associations. These observations support the utility of sleep spindles as useful cognitive function markers in obstructive sleep apnea, which warrants further longitudinal investigation.

Associations of Baseline Sleep Microarchitecture with Cognitive Function After 8 Years in Middle-Aged and Older Men from a Community-Based Cohort Study.

Purpose: Prospective studies examining associations between baseline sleep microarchitecture and future cognitive function recruited from small samples with predominantly short follow-up. This study examined sleep microarchitecture predictors of cognitive function (visual attention, processing speed, and executive function) after 8 years in community-dwelling men. Patients and Methods: Florey Adelaide Male Ageing Study participants (n=477) underwent home-based polysomnography (2010-2011), with 157 completing baseline (2007-2010) and follow-up (2018-2019) cognitive assessments (trail-making tests A [TMT-A] and B [TMT-B] and the standardized mini-mental state examination [SMMSE]). Whole-night F4-M1 sleep EEG recordings were processed following artifact exclusion, and quantitative EEG characteristics were obtained using validated algorithms. Associations between baseline sleep microarchitecture and future cognitive function (visual attention, processing speed, and executive function) were examined using linear regression models adjusted for baseline obstructive sleep apnoea, other risk factors, and cognition. Results: The final sample included men aged (mean [SD]) 58.9 (8.9) years at baseline, overweight (BMI 28.5 [4.2] kg/m2), and well educated (75.2% ≥Bachelor, Certificate, or Trade), with majorly normal baseline cognition. Median (IQR) follow-up was 8.3 (7.9, 8.6) years. In adjusted analyses, NREM and REM sleep EEG spectral power was not associated with TMT-A, TMT-B, or SMMSE performance (all p>0.05). A significant association of higher N3 sleep fast spindle density with worse TMT-B performance (B=1.06, 95% CI [0.13, 2.00], p=0.026) did not persist following adjustment for baseline TMT-B performance. Conclusion: In this sample of community-dwelling men, sleep microarchitecture was not independently associated with visual attention, processing speed, or executive function after 8 years.

The association between sleep microarchitecture and cognitive function in middle-aged and older men: a community-based cohort study.

STUDY OBJECTIVES: Sleep microarchitecture parameters determined by quantitative power spectral analysis of electroencephalograms have been proposed as potential brain-specific markers of cognitive dysfunction. However, data from community samples remain limited. This study examined cross-sectional associations between sleep microarchitecture and cognitive dysfunction in community-dwelling men. METHODS: Florey Adelaide Male Ageing Study participants (n = 477) underwent home-based polysomnography (2010-2011). All-night electroencephalogram recordings were processed using quantitative power spectral analysis following artifact exclusion. Cognitive testing (2007-2010) included the inspection time task, Trail-Making Tests A and B, and Fuld object memory evaluation. Complete case cognition, polysomnography, and covariate data were available in 366 men. Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders determined cross-sectional associations between sleep microarchitecture and cognitive dysfunction overall and by age-stratified subgroups. RESULTS: In the overall sample, worse Trail-Making Test A performance was associated with higher rapid eye movement (REM) theta and alpha and non-REM theta but lower delta power (all P < .05). In men ≥ 65 years, worse Trail-Making Test A performance was associated with lower non-REM delta but higher non-REM and REM theta and alpha power (all P < .05). Furthermore, in men ≥ 65 years, worse Trail-Making Test B performance was associated with lower REM delta but higher theta and alpha power (all P < .05). CONCLUSIONS: Sleep microarchitecture parameters may represent important brain-specific markers of cognitive dysfunction, particularly in older community-dwelling men. Therefore, this study extends the emerging community-based cohort literature on a potentially important link between sleep microarchitecture and cognitive dysfunction. The utility of sleep microarchitecture for predicting prospective cognitive dysfunction and decline warrants further investigation. CITATION: Parker JL, Appleton SL, Melaku YA, et al. The association between sleep microarchitecture and cognitive function in middle-aged and older men: a community-based cohort study. J Clin Sleep Med. 2022;18(6):1593-1608.

The association between obstructive sleep apnea and sleep spindles in middle-aged and older men: a community-based cohort study.

STUDY OBJECTIVES: Sleep spindles show morphological changes in obstructive sleep apnea (OSA). However, previous small studies have limited generalizability, leaving associations between OSA severity measures and spindle metrics uncertain. This study examined cross-sectional associations between OSA severity measures and spindle metrics among a large population-based sample of men. METHODS: Community-dwelling men with no previous OSA diagnosis underwent home-based polysomnography. All-night EEG (F4-M1) recordings were processed for artifacts and spindle events identified using previously validated algorithms. Spindle metrics of interest included frequency (Hz), amplitude (µV2), overall density (11-16 Hz), slow density (11-13 Hz), and fast density (13-16 Hz) (number/minute). Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders were used to examine cross-sectional associations between OSA severity measures and spindle metrics. RESULTS: In adjusted analyses, higher apnea-hypopnea index (AHI/h, as a continuous variable) and percentage total sleep time with oxygen saturation <90% (TST90) were associated with decreased slow spindle density (AHI, B = -0.003, p = 0.032; TST90, B = -0.004, p = 0.047) but increased frequency (AHI, B = 0.002, p = 0.009; TST90, B = 0.002, p = 0.043). Higher TST90 was also associated with greater spindle amplitude (N2 sleep, B = 0.04, p = 0.011; N3 sleep, B = 0.11, p < 0.001). Furthermore, higher arousal index was associated with greater spindle amplitude during N2 sleep (B = 0.31, p < 0.001) but decreased overall density (B = -1.27, p = 0.030) and fast density (B = -4.36, p = 0.028) during N3 sleep. CONCLUSIONS: Among this large population-based sample of men, OSA severity measures were independently associated with spindle abnormalities. Further population studies are needed to determine associations between spindle metrics and functional outcomes.