Total sleep deprivation increases brain age prediction reversibly in multi-site samples of young healthy adults.

Sleep loss pervasively affects the human brain at multiple levels. Age-related changes in several sleep characteristics indicate that reduced sleep quality is a frequent characteristic of aging. Conversely, sleep disruption may accelerate the aging process, yet it is not known what will happen to the age status of the brain if we can manipulate the sleep conditions. To tackle this question, we employed an approach of brain age to investigate whether sleep loss would cause age-related changes in the brain. We included MRI data of 134 healthy volunteers (mean chronological age of 25.3, between the age of 19 and 39, 42 females/92 males) from five datasets with different sleep conditions. Across three datasets with the condition of total sleep deprivation (> 24 hours of prolonged wakefulness), we consistently observed that total sleep deprivation increased brain age by 1-2 years regarding the group mean difference with the baseline. Interestingly, after one night of recovery sleep, brain age was not different from baseline. We also demonstrated the associations between the change in brain age after total sleep deprivation and the sleep variables measured during the recovery night. By contrast, brain age was not significantly changed by either acute (3 hours' time-in-bed for 1 night) or chronic partial sleep restriction (5 hours' time-in-bed for 5 continuous nights). Taken together, the convergent findings indicate that acute total sleep loss changes brain morphology in an aging-like direction in young participants and that these changes are reversible by recovery sleep. SIGNIFICANCE STATEMENT: Sleep is fundamental for humans to maintain normal physical and psychological functions. Experimental sleep deprivation is a variable-controlling approach to engaging the brain among different sleep conditions for investigating the brain's responses to sleep loss. Here, we quantified the brain's response to sleep deprivation by using the change of brain age predictable with brain morphological features. In three independent datasets, we consistently found increased brain age after total sleep deprivation, which was associated with the change in sleep variables. Moreover, no significant change in brain age was found after partial sleep deprivation in another two datasets. Our study provided new evidence to explain the brain-wide effect of sleep loss in an aging-like direction.