Aging is associated with increased propensity for central apnea during NREM sleep

Abstract

The reason for increased sleep-disordered breathing with predominance of central apneas in the elderly is unknown. We hypothesized that the propensity to central apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO₂) reserve in older compared with young adults during non-rapid eye movement sleep. Ten elderly and 15 young healthy adults underwent multiple brief trials of nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The CO₂ reserve was defined as the difference in end-tidal CO₂ ([Formula: see text]) between eupnea and the apneic threshold, where the apneic threshold was [Formula: see text] that demarcated the central apnea closest to the eupneic [Formula: see text]. For each MV trial, the hypocapnic ventilatory response (controller gain) was measured as the change in minute ventilation (V̇e) during the MV trial for a corresponding change in [Formula: see text]. The eupneic [Formula: see text] was significantly lower in elderly vs. young adults. Compared with young adults, the elderly had a significantly reduced CO₂ reserve (-2.6 ± 0.4 vs. -4.1 ± 0.4 mmHg, P = 0.01) and a higher controller gain (2.3 ± 0.2 vs. 1.4 ± 0.2 l·min^-1·mmHg^-1, P = 0.007), indicating increased chemoresponsiveness in the elderly. Thus elderly adults are more prone to hypocapnic central apneas owing to increased hypocapnic chemoresponsiveness during NREM sleep. NEW & NOTEWORTHY The study describes an original finding where healthy older adults compared with healthy young adults demonstrated increased breathing instability during non-rapid eye movement sleep, as suggested by a smaller carbon dioxide reserve and a higher controller gain. The findings may explain the increased propensity for central apneas in elderly adults during sleep and potentially guide the development of pathophysiology-defined personalized therapies for sleep apnea in the elderly.

Keywords: CO2 reserve; aging; apneic threshold; chemoresponsiveness; controller gain; elderly; hypocapnic ventilatory response; plant gain.

Fig. 1.

Grouped data comparing the eupneic end-tidal CO₂ (A) and eupneic V̇e (B) in the 2 age groups: young and elderly. The bars represent averaged data for each age group (black bar = young, n = 15; gray bar = elderly age, n = 10). The eupneic $\mathrm{P}\mathrm{E}{\mathrm{T}}_{\mathrm{C}{\mathrm{O}}_{\mathrm{2}}}$ was significantly lower (*P = 0.006), whereas V̇e was significantly higher in the elderly vs. young age groups (#P = 0.01).

Fig. 2.

Grouped data comparing the CO₂ reserve (A) and apneic threshold (B). The bars represent averaged data for each age group (black bar = young, n = 15; gray bar = elderly age, n = 10). The CO₂ reserve was reduced in elderly vs. young adults, denoting an increased propensity to central apneas (*P = 0.01). The apneic threshold was significantly reduced in the elderly (§P = 0.049) (see text for explanation).

Fig. 3.

Grouped data comparing the controller gain (A) and plant gain (B) in the two age groups: young and elderly age. The bars represent averaged data for each age group (black bar = young; gray bar = elderly age, respectively). The controller gain was significantly higher in the elderly compared with young (*P = 0.007), whereas, the plant gain was not significantly different between the age groups.