Decreased Gray-White Matter Contrast of [11C]-PiB Uptake in Cognitively Unimpaired Subjects with Severe Obstructive Sleep Apnea

Background Very recently, cognitively normal, middle-aged adults with severe obstructive sleep apnea (OSA) were shown to have regional cortical amyloid-beta deposits. In the normal brain, amyloid tracer (e.g., [C-11]-PiB) uptake is observed in white matter (WM) but not in cortical gray matter (GM), resulting in clear GM-WM contrast. There are no reports on possible changes in this contrast in severe OSA. Objectives Evaluate changes in the global [C-11]-PiB GM-WM contrast and study if factors reflecting clinical and imaging characteristics are associated with them. Design and Setting Cross-sectional imaging study. Participants 19 cognitively intact middle-aged (mean 44 years) patients with severe OSA (Apnea-Hypopnea Index >30/h), carefully selected to exclude any other possible factors that could alter brain health. Measurements Detailed neuroimaging (amyloid PET, MRI). Signs of possible alterations in amyloid tracer GM-WM contrast and kinetics were studied with static and dynamic [C-11]-PiB PET and WM structures with detailed 3.0T MRI. Results Static [C-11]-PiB PET uptake showed significantly decreased GM-WM contrast in 5 out of 19 patients. This was already clearly seen in visual evaluation and also detected quantitatively using retention indexes. Dynamic imaging revealed decreased contrast due to alterations in trace accumulation in the late phase of [C-11]-PiB kinetics. Decreased GM-WM contrast in the late phase was global in nature. MRI revealed no corresponding alterations in WM structures. Importantly, decreased GM-WM contrast was associated with smoking (p = 0.007) and higher Apnea-Hypopnea Index (p = 0.001). Conclusions Severe OSA was associated with decreased GM-WM contrast in amyloid tracer uptake, with significant correlation with clinical parameters of smoking and AHI. The results support and further extend the current understanding of the deleterious effect of severe OSA on proper amyloid clearance, possibly reflecting dysfunction of the brain glymphatic system.

Automated summary

Cognitively normal middle-aged adults with severe obstructive sleep apnea (OSA) were found to have decreased gray matter-white matter contrast in cortical amyloid-beta deposits. This decrease was associated with smoking and higher Apnea-Hypopnea Index, highlighting the detrimental effect of OSA on amyloid clearance and suggesting dysfunction of the brain glymphatic system.