Overnight Dynamics of Ventricular Cerebrospinal Fluid Amyloid‐Beta, Lactate and Hypocretin in Patients With Hydrocephalus: A Pilot Study

🎖️ Top 10% JournalJan 29, 2026Journal of sleep research

Nighttime Changes in Brain Fluid Levels of Amyloid-Beta, Lactate, and Wakefulness Hormone in Hydrocephalus Patients

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Abstract

Hourly ventricular cerebrospinal fluid sampling is feasible in adults with hydrocephalus.

Sleep was significantly disrupted, with obstructive sleep apnea frequently observed among participants.
Amyloid-β42 levels increased in the evening, plateaued during peak non-rapid eye movement sleep, and rose sharply after 8 AM.
Hypocretin and lactate concentrations were positively correlated and occurred prior to increases in amyloid-β42.
Melatonin peaked around 6 AM and was associated with non-rapid eye movement sleep.
Intracranial pressure followed a distinct circadian rhythm, peaking during non-rapid eye movement sleep, while hypocretin and amyloid-β42 showed only modest rhythmicity.
Preliminary evidence suggests that wakefulness-related processes may primarily influence overnight amyloid-β42 variation.

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This pilot observational study evaluated whether frequent overnight sampling of ventricular cerebrospinal fluid could clarify how sleep, hypocretin and lactate relate to amyloid-β42 dynamics in adults with hydrocephalus. Seven participants underwent hourly ventricular cerebrospinal fluid sampling from early evening to late morning during inpatient monitoring, combined with full polysomnography. Concentrations of amyloid-β42, hypocretin, lactate, melatonin and electrolytes were measured and normalised to each individual's mean. Relationships with sleep stage and circadian patterns were examined using correlation analysis and cosinor modelling. Sleep was markedly disrupted, with obstructive sleep apnea common and analysable sleep data available for six participants. Non-rapid eye movement sleep peaked at approximately 4 AM Amyloid-β42 rose in the evening, plateaued during peak non-rapid eye movement sleep and increased sharply after 8 AM Hypocretin and lactate were positively correlated and each preceded and correlated with amyloid-β42 surges. Melatonin peaked near 6 AM and was associated with non-rapid eye movement sleep. Intracranial pressure displayed a strong circadian rhythm, peaking during non-rapid eye movement sleep, whereas hypocretin and amyloid-β42 exhibited only modest rhythmicity. These findings demonstrate that overnight ventricular cerebrospinal fluid sampling is feasible in adults with hydrocephalus. Preliminary evidence suggests that processes linked to wakefulness, rather than sleep or intrinsic circadian timing, may be the primary drivers of overnight amyloid-β42 variation. Hypocretin pathways may represent potential therapeutic targets in Alzheimer's disease, but conclusions are limited by abnormal sleep architecture and underlying neurological disease. Validation in larger and more representative populations is warranted.

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