TABLE 4.

The effects of sleep apnea on aging markers and age-related diseases.

Author, year (ref.)	Condition	Age in years	Study design	Total quality score#	Type of sleep apnea	Sleep apnea criteria	Aging markers	Results	Conclusion
Addison-Brown et al., 2014	SA	47–93	Case-control		OSA	High risk of OSA based on the Berlin Sleep Questionnaire.	Cognitive function	Those at high risk for OSA had significantly lower cognitive scores. However, some of the associations were age-dependent. Differences in cognition between those at high and low OSA risk were most pronounced during middle age, with attenuated effects after age 70 years.	Authors able to confirm OSA’s effect on cognition, depressive symptoms and HRQoL. They also found differential effects based on age, with more detrimental correlates of OSA in younger versus older adults, particularly in terms of mood and HRQoL.
				8			Depression	Those at high risk for OSA had significantly higher depressive symptoms.
							HRQoL	Those at high risk for OSA had significantly lower HRQoL. However, some of the associations were age-dependent. Differences in quality of life between those at high and low OSA risk were most pronounced during middle age, with attenuated effects after age 70 years.
Ayalon et al., 2010	SA	25–59	Case-control	6	OSA	AHI >10.	Cognitive performance and brain activation	Middle-aged patients with OSA showed reduced performance for immediate word recall and slower reaction time during sustained attention. For both tasks, decreased activation was detected for middle-aged sleep apnea relative to the other groups in task-related brain regions.	The presence of both sleep apnea and increasing age overwhelmed the brain’s capacity to respond to cognitive challenges with compensatory recruitment and to maintain performance.
Duffy et al., 2016	SA, and at risk for dementia	Mean, 65	Cross-sectional	7	OSA	SA was determined based on O2-desaturation and AHI, rapid eye movement sleep, and non-rapid eye movement sleep.	GSH and creatine	Increased levels of GSH/Cr were associated with lower oxygen desaturation and more severe apnea-hypopnea index scores during rapid eye movement sleep. In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition and set shifting).	Markers of nocturnal hypoxemia and sleep disordered breathing (SDB) are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia.
Edwards et al., 2014	SA	20-40 (young) and >60 (old)	Case-control	7	OSA	OSA patients with AHI > 10 events/h and were treated with CPAP for more than 5 h per night for at least 2 months prior to enrollment.	Pharyngeal anatomy/collapsibility	In comparison with younger patients with OSA, older patients had a more collapsible airway.	The data suggest that airway anatomy/collapsibility plays a relatively greater pathogenic role in older adults, whereas a sensitive ventilator control system is a more prominent trait in younger adults with OSA.
							Loop gain (LG)	In comparison with younger patients with OSA, older patients had a lower LG
							UAG	It was similar between groups.
							RAT	It was similar between groups.
Khan et al., 2011	SA	>65	Cohort	9	OSA	OSA was diagnosed when AHI was >5 events/h.	Hct and Hgb	Hct changed significantly post OSA treatment. The change in Hgb after OSA treatment was not significant. However, the change in Hgb was large enough to reach WHO standards for AoA. Hct changed significantly among both men and women.	There was no AOA before OSA treatment. But there was AOA 1 year after OSA treatment. Authors believe OSA inflammatory processes interact with OSA hypoxia-induced erythropoiesis.
Kritikou et al., 2014	SA	Mean 42–66	Case-control		OSA	AHI > 10 events/h of sleep for females and >15 events/h for males.	Sleepiness	Apnoeic males were significantly sleepier than controls. CPAP improved subjective sleepiness.	OSA is associated with sleepiness, inflammation and insulin resistance, even in non-obese males, and this association is stronger in males than in females. Short-term CPAP does not improve the inflammatory/metabolic aberrations in OSA.
				8			IL-6	Apnoeic males had significantly higher IL-6 than controls. Apnoeic females had IL-6 similar to controls. CPAP did not change IL-6
							TNFR-1	No significant difference was observed in TNFR-1 values. CPAP did not change TNFR-1
							Leptin and adiponectin	Apnoeic males had significantly higher leptin than controls. Apnoeic females had leptin and adiponectin similar to controls. CPAP did not change leptin and adiponectin
							hsCRP	Apnoeic males and females had significantly higher hsCRP. CPAP did not change hsCRP.
							Fasting glucose and insulin levels	Apnoeic males had significantly higher insulin resistance than controls. Apnoeic females had insulin resistance similar to controls. CPAP did not change insulin resistance.
Sajkov et al., 1998	SA and tetraplegia	18–60	Case-control	7	OSA	AHI > 15 per hour of sleep.	Neuropsychological function (e.g., memory, perception, attention, and concentration)	The neuropsychological functions most affected by nocturnal desaturation were verbal attention and concentration, immediate and short-term memory, cognitive flexibility, internal scanning and working memory.	SA impairs daytime cognitive function in tetraplegia patients, particularly attention, concentration, memory and learning skills. Cognitive disturbances resulting from SA might adversely affect rehabilitation in patients with tetraplegia.
Vgontzas et al., 2019	SA	20–80	Cohort	9	OSA	Mild OSA = AHI 5–14.9 events/h, and moderate OSA = AHI 15–29.9 events/h. All cases were without hypertension at the baseline.	Incident hypertension	Mild-to-moderate OSA was significantly associated with increased risk of incident hypertension. Importantly, this association was modified by age; while strong in young and middle-aged adults, the association was lost in adults older than 60 years. Furthermore, the association of mild-to-moderate OSA with components of metabolic syndrome was strongest in young and middle-aged adults.	Mild-to-moderate OSA, even when asymptomatic, is associated with increased risk of incident hypertension, but the strength of association significantly decreases with age.
Weihs et al., 2021	SA	Mean 52.5	Cross-sectional	7	OSA	Mild to severe OSA (AHI and ODI ≥ 5) and severe OSA (AHI and ODI ≥ 15).	A score quantifying age-related brain patterns in 169 brain regions	AHI and ODI were both positively associated with brain age. The effects remained stable in the presence of various confounders such as diabetes and were partially mediated by the white blood cell count, indicating a subclinical inflammation process.	The study reveals an association between OSA and brain age, indicating subtle but widespread age-related changes in regional brain structures.
Yim-Yeh et al., 2010	SA	18–70	Cross-sectional	6	OSA	AHI>10/h.	Vascular function, and arterial stiffness	FMD was impaired in patients with OSA. OSA did not significantly influence vascular function in the skin microcirculation. The augmentation index, a measure of arterial stiffness, was similar between the OSA and control groups, OSA independently predicted the augmentation index in men only.	In obesity, both OSA and aging impair endothelial function and increase arterial stiffness.

^#Total quality score out of 9 for cohort/case-control and out of 7 for cross-sectional; SA, sleep apnea; OSA, obstructive sleep apnea; HRQoL, health-related quality of life; AHI, apnea–hypopnea index; fMRI, functional magnetic resonance imaging; CPAP, continuous positive airway pressure; ESS, Epworth Sleepiness Scale; MSLT, multiple sleep latency test; PVT, the psychomotor vigilance test; IL-6, interleukin-6; TNFR-1, tumor necrosis factor receptor-1; hsCRP, high-sensitivity C-reactive protein; ODI, oxygen desaturation index; FMD, flow-mediated dilation; 1H-MRS, proton magnetic resonance spectroscopy; GSH, glutathione; UAG, upper airway muscle responsiveness/gain; RAT, respiratory arousal threshold.