Impact of Continuous Positive Airway Pressure Therapy on Bilateral Local Hippocampal Gray Matter Volume in Elderly Patients With Obstructive Sleep Apnea - Study BBBSAS

Condition(s) studied

Investigational drug(s) / intervention(s)

Continuous Positive Airway Pressure (CPAP) therapy: Standard-of-care nocturnal CPAP ventilation, initiated per usual clinical practice in patients diagnosed with severe OSA and continued for approximately 6 months. Treatment tolerance, efficacy, and average adherence (target ≥5 hours/night) are checked at a clinical visit after 4 months of treatment.

Multimodal brain MRI with Gadolinium injection: One-hour, 6-sequence brain MRI protocol (3D T1 MP2RAGE, T2 relaxometry, 60-direction diffusion tensor imaging, T2\* susceptibility-weighted imaging, dynamic contrast-enhanced perfusion imaging, and post-Gadolinium 3D T1 MPRAGE), used to quantify blood-brain barrier permeability (permeability-surface area product) and local gray/white matter volume by voxel-based morphometry and automated hippocampal segmentation. Gadobutrol (Gadovist®) 0.1 mmol/kg is injected intravenously during the 5th sequence via a venous catheter placed before the first sequence. Performed once in control subjects and twice in patients (before and after approximately 6 months of CPAP).

Study summary

This study evaluates whether treating severe obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) for approximately 6 months modifies local hippocampal and frontal cortex gray matter volume and blood-brain barrier (BBB) permeability in elderly men. Twenty-five men aged 70 years or older with newly diagnosed, previously untreated severe OSA (apnea-hypopnea index \[AHI\] \> 30) are compared with 25 age- and body-mass-index-matched control men without OSA (AHI \< 10, oxygen desaturation index \< 10).

All participants undergo a comprehensive neurocognitive assessment, instrumented gait and balance analysis, blood and urine sampling for systemic inflammatory and aquaporin markers, and a multimodal brain MRI with intravenous Gadolinium injection to quantify BBB permeability and gray/white matter volume. Patients repeat the MRI, cognitive testing, and gait/balance assessment after approximately 6 months of CPAP therapy, once adequate treatment adherence (≥5 hours/night).

The main hypothesis is that severe untreated OSA is associated with focal BBB permeability abnormalities in the hippocampus and frontal cortex, and that effective CPAP treatment partially reverses these anatomical and functional changes, together with improvements in executive/memory performance, gait, balance, and systemic inflammation. Results are expected to clarify the neurocognitive impact of OSA in the elderly, help target patients who most need treatment, and identify complementary pharmacological targets.

Eligibility

Primary outcome measure(s)

• Blood-brain barrier (BBB) permeability abnormality in the hippocampus and frontal cortex — months 6
  Assessed using a multimodal MRI protocol (3D T1 MP2RAGE, T2 relaxometry, diffusion tensor imaging, T2\* susceptibility-weighted imaging, dynamic contrast-enhanced perfusion imaging providing the permeability-surface area product \[PS\], and post-Gadolinium 3D T1 MPRAGE), analyzed by voxel-based morphometry and automated hippocampal segmentation.

Trial sites (1)

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