Cerebrospinal Fluid Orexin Levels and Nocturnal Sleep Disruption in Alzheimer's Disease Patients Showing Neuropsychiatric Symptoms

Background: Alzheimer's disease (AD) is the most common form of dementia. It is characterized by a progressive deterioration of cognition, frequently associated with neuropsychiatric symptoms (NPS). Among NPS, sleep disturbances often affect AD patients. Orexinergic system dysregulation has been associated with sleep impairment in AD patients. Objective: The present study investigated CSF orexin levels in AD patients and their relationship with both NPS, measured by the neuropsychiatric inventory (NPI), and sleep, measured via polysomnography. Methods: This is a secondary analysis of a previous study investigating CSF biomarkers, sleep impairment and cognitive decline in AD patients. AD patients completing the NPI were included in this analysis and distributed in two groups based on the presence (NPI score ≥4, AD/NPS+) or absence (NPI score <4, AD/NPS-) of NPS. Results: Twenty-Two AD patients constituted the AD/NPS+ group and 20 patients constituted the AD/NPS-group. We observed higher CSF orexin levels in AD/NPS+ than AD/NPS-patients. Moreover, AD/NPS+ showed a more fragmented and the reduction of REM sleep compared to AD/NPS-patients. Notably, higher NPI scores correlated with a more altered sleep structure, higher CSF orexin levels and lower MMSE scores. Conclusion: This study documented that AD patients showing NPS present a more fragmented sleep coupled with higher CSF orexin levels compared to AD patients not affected by NPS. This finding showing the increased orexinergic tone in AD patients affected by NPS suggests the possible influence of the orexinergic system dysregulation not only on sleep impairment but also on neurobehavioral disturbances.