Understanding the role of sleep disturbance on cognitive decline in aging persons with schizophrenia: A critical review

Cognitive impairment is a core feature of schizophrenia that worsens with aging and interferes with quality, functioning and independence in everyday life. Recent work identifies sleep as an actionable target to alleviate cognitive deficits. Cardinal non-rapid eye movement (NREM) sleep oscillations such as sleep spindles and slow oscillations are critical for cognition. People living with schizophrenia (PLWS) and their first-degree relatives have a specific reduction in sleep spindles and an abnormality in their temporal coordination with slow oscillations that predicts impaired memory consolidation. Spindles are propagated via thalamocortical feedback loops, and this circuitry shows abnormal hyperconnectivity in schizophrenia as revealed by structural and functional MRI studies. Although this line of research identifies a well-defined NREM circuitry that is abnormal in schizophrenia and is associated with cognitive deficits, it is not known how this circuitry changes with aging in PLWS. One understudied risk factor for cognitive deficits among older PLWS is untreated obstructive sleep apnea (OSA), a sleep disorder where airway collapse results in intermittent hypoxia and, when untreated, can contribute to cognitive decline. While the risk and severity of OSA increases with age, older PLWS are particularly vulnerable to OSA-related cognitive deficits because OSA is often underdiagnosed and undertreated, and OSA adds further damage to the circuitry that generates NREM sleep oscillations. We highlight the critical need to study NREM sleep in older PWLS and propose that identifying and treating OSA in older PLWS will provide an avenue to potentially mitigate and prevent cognitive decline.