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Sleep-disordered breathing (SDB) was tied to medial temporal lobe volumes in amyloid-positive older adults who were cognitively unimpaired, data from the randomized trial showed.

Among cognitively intact adults with amyloid plaques, higher sleep apnea severity was associated with gray matter atrophy in regions affected early by Alzheimer's disease pathology, reported Géraldine Rauchs, PhD, of Normandie University in France, and co-authors.

Sleep apnea severity -- based on the apnea-hypopnea index (AHI) -- was related to lower medial temporal lobe subregion volumes in amyloid-positive individuals, but not in those who were amyloid-negative, the researchers wrote in . Specifically, AHI and amyloid status significantly interacted on volumes of the:

• Entorhinal cortex (P<0.001)
• Whole hippocampus (P<0.001)
• Subiculum (P=0.002)
• Cornu ammonis 1 (P=0.002)
• Dentate gyrus (P=0.003)

Similarly, greater oxygen desaturation index was associated with entorhinal cortex and hippocampus volumes in amyloid-positive patients only.

"Alzheimer's disease is known to affect the entorhinal cortex before cornu ammonis 1 and subiculum subfields, due to the spreading of tau pathology in early stages of the disease," the group wrote. "Interestingly, medial temporal lobe subregions are also known to be sensitive to hypoxia, a major consequence of SDB. Animal studies indicate that cornu ammonis 1 may be the most vulnerable region to hypoxia within the medial temporal lobe, while other subfields like cornu ammonis 3 are spared."

"Our results suggest that some people may be more vulnerable to the adverse effects of sleep apnea," Rauchs said in a press release.

"People who are in the very early stages of the Alzheimer's continuum showed a specific vulnerability to sleep apneas," she added. "Further studies should look at whether treating sleep-disordered breathing could potentially improve cognition and prevent or delay neurodegeneration."

These findings may provide insights into the effects of SDB on the brains of healthy individuals.

"The fact that no association between SDB and medial temporal lobe integrity was found in amyloid-negative participants contrasts with some previous reports showing SDB-related hippocampal changes in younger populations who are unlikely to exhibit significant Alzheimer's disease pathology (i.e., young middle-aged individuals and children with obstructive sleep apnea)," the researchers wrote.

"We can speculate that SDB may exacerbate Alzheimer's disease pathology in all participants, but amyloid-negative individuals may not suffer from SDB since [there was not] enough time to exhibit neurodegeneration yet, or may be more resilient to the adverse effects of SDB than amyloid-positive individuals," they added.

"Importantly, in our cohort, only a small proportion of participants with moderate-to-severe SDB exhibited symptoms of excessive daytime sleepiness (11 out of 91 participants)," Rauchs and co-authors pointed out. "In addition, they were overall highly educated, had no cognitive deficits and may therefore present with a high cognitive reserve. However, amyloid-negative participants may still be at risk of neurodegeneration over the long-term."

No significant associations emerged between SDB parameters at baseline and memory scores the end of the study. Across the whole study cohort, lower baseline volume measurements for the whole hippocampus (P=0.005) and CA1 (P=0.003) were associated with worse episodic memory performance at follow-up.

Further adjustments for patient sex indicated that higher AHI scores were associated with the loss of gray matter in the hippocampus, entorhinal cortex, parahippocampal cortex, cornu ammonis 1, and dentate gyrus only among women.

For this study, Rauchs and colleagues used data from the Age-Well trial of the Medit-Ageing European project from 2016 to 2020.

A total of 122 participants were included in the study. Of these, 63.1% were women, average age was 69.4 years, and 21.3% were amyloid-positive. Amyloid-positive patients tended to be significantly older and more likely to be APOE4 carriers than their amyloid-negative counterparts.

Sleep was assessed with home-based polysomnography. Participants had cognitive tests, MRI, and PET at baseline. Cognition was assessed again at a mean of 20.66 months later.

"Further studies should evaluate the impact of tau pathology, and assess the potentially beneficial effects of SDB treatment," the researchers concluded.

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