A recent study involving 60 adults with mild-to-moderate Alzheimer’s disease has shown that higher levels of orexin, a neurotransmitter associated with wakefulness, are linked to worse cognitive outcomes and behavioral symptoms. The research, conducted by an international team led by Concordia University, also found that stronger sleep spindles and slow brain oscillations during non-rapid eye movement (NREM) sleep may help mitigate some of the negative effects of high orexin levels.
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The observational study, which lasted up to three years, monitored participants' brain activity through overnight polysomnography in Lleida, Spain, collecting cerebrospinal fluid samples to measure orexin-A and various biomarkers associated with neurodegeneration and inflammation. It revealed that while overall sleep duration and efficiency were not significantly related to orexin levels, specific patterns of brain activity during NREM sleep played a critical role in cognitive outcomes.
Participants performed cognitive tests repeatedly over the study period, which included assessments of global cognition, verbal learning, visual memory, and neuropsychiatric symptoms. Notably, higher cerebrospinal fluid orexin levels, averaging 757.3 picograms per milliliter, were found to correlate with worse performance on established cognitive scales.
The study highlighted that sleep spindles and slow oscillations, both crucial for memory and cognitive functioning, could offer protective benefits against the cognitive declines associated with heightened orexin. The findings showed that greater spindle density and longer slow oscillations were generally associated with lower orexin levels, thus suggesting a potential buffering effect where improved sleep wave patterns could lessen the cognitive impact of elevated orexin.
While the study indicates a connection between orexin and cognitive decline, authors cautioned against drawing causal conclusions due to the observational nature of the research and the absence of a cognitively healthy control group. Additionally, many participants experienced moderate-to-severe obstructive sleep apnea, yet adjusting for this did not significantly alter the main relationships observed.
The research team encourages further studies with larger participant groups and repeated sleep assessments to clarify whether NREM sleep metrics can help identify individuals who might benefit from treatments focused on sleep. The potential implications of orexin-blocking medications, currently explored for insomnia, could extend to future Alzheimer's treatment pathways.