Literature Review

Sleep-disordered breathing linked with Alzheimer’s disease biomarkers in cognitively normal older adults


 

FROM JAMA NEUROLOGY

Among community-dwelling adults aged 65 years and older with sleep-disordered breathing, Alzheimer’s-associated brain changes may occur in the absence of cognitive impairment, investigators have found.

Among 127 adults enrolled in a randomized clinical trial of interventions to promote mental well-being in older adults, those with sleep-disordered breathing had significantly greater amyloid burden and gray-matter volume, as well as increased perfusion and metabolism in parietal-occipital regions, reported Claire André, PhD, from the French Institute of Health and Medical Research (INSERM) unit in Caen, and colleagues.

“Our findings highlight the need to treat sleep disorders in the older population, even in the absence of cognitive or behavioral manifestations,” they wrote in a study published in JAMA Neurology.

Previous studies of the possible association between sleep-disordered breathing and dementia risk have shown conflicting or inconsistent results, the authors noted.

“These discrepancies may be explained by the characteristics of patients with sleep-disordered breathing (e.g., recruited from sleep clinics versus from the community, differences in age and disease duration), the scoring criteria of respiratory events, sample sizes, or the lack of controls for possibly biasing covariates,” they wrote.

To see whether they could clear up the confusion, the investigators conducted a retrospective analysis of 127 patients who were enrolled in the Age-Well randomized, controlled trial of the Medit-Ageing European project. The participants were community-dwelling adults (mean age, 69.1 years; 63% women), who were enrolled in the trial and underwent evaluation from 2016 to 2018 at the Cyceron Cancer Center in Caen.

The participants, all of whom were cognitively unimpaired at baseline, underwent neuropsychological assessment, polysomnography, MRI, plus florbetapir- and fluorodeoxyglucose-labeled PET.

The investigators defined sleep-disordered breathing as 15 apnea-hypopnea index events per hour or higher, and compared results between those with sleep-disordered breathing and those without for each imaging modality.

Participants with sleep-disordered breathing has significantly greater amyloid burden (P = .04), gray-matter volume (P = .04), perfusion (P = .04), and metabolism (P = .001), primarily overlapping the posterior cingulate cortex and precuneus, areas known to be significantly involved in Alzheimer’s disease.

When the investigators looked for behavioral and cognitive correlates of sleep-disordered breathing severity with associated brain changes, however, they found no associations with either cognitive performance, self-reported cognitive or sleep difficulties, or symptoms of daytime sleepiness.

“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalizes with greater gray-matter volume, perfusion, and metabolism in older participants with sleep-disordered breathing who are cognitively unimpaired. We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms,” they wrote.

The Age-Well randomized clinical trial is part of the Medit-Ageing project and is funded through the European Union’s Horizon 2020 Research and Innovation Program, INSERM, and Fondation d’ Entreprise MMA des Entrepreneurs du Futur. Dr. André reported no conflicts of interest to disclose.

SOURCE: André C et al. JAMA Neurol. 2020 Mar 23. doi: 10.1001/jamaneurol.2020.0311.

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