Sleep apnea is associated with entorhinal cortex and hippocampal subfield atrophy in asymptomatic amyloid‐positive older adults

Abstract

AbstractBackgroundSleep‐disordered breathing (SDB) has been associated to greater amyloid deposition and dementia risk. However, the pattern of SDB‐associated structural brain changes is unclear, especially within the medial temporal lobe (MTL). We investigated the associations between SDB severity and the volume of MTL subregions, and hypothesized that SDB would be associated with atrophy in regions early affected by Alzheimer’s disease (AD) pathology and/or sensitive to hypoxia (i.e., the perirhinal and entorhinal cortices, and CA1 hippocampal subfield), particularly in amyloid‐positive participants.MethodWe included 120 cognitively unimpaired older participants from the Age‐Well randomized controlled trial (mean age=69 ± 3,8 years; 25 Aβ+ and 95 Aβ‐ participants). They underwent a structural MRI, including a high‐resolution T2‐weighted sequence of the MTL (0.4x0.4x2.5mm3), a Florbetapir‐PET scan to measure amyloid deposition, as well as a polysomnography. The ASHS (Automatic Segmentation of Hippocampal Subfields) software was used to segment the entorhinal, perirhinal, and parahippocampal cortices, as well as hippocampal subfields (i.e., the subiculum, CA1, CA2‐3, the dentate gyrus, their sum representing total hippocampal volume) on high‐resolution MRI sequences. Bilateral volumes normalized to the total intracranial volume were used in statistical analyses. We performed linear regressions with the volume of each MTL subregion as dependent variables, the apnea‐hypopnea index (AHI, reflecting SDB severity) and amyloid status as independent variables, and age, sex, education and the ApoE4 status as covariates.ResultWe found significant interactions between the AHI and amyloid status on the volumes of the entorhinal cortex (p<0.001), whole hippocampus (p<0.001), subiculum (p<0.001), CA1 (p=0.003) and dentate gyrus (p=0.007), such that the AHI significantly predicted the volume of these MTL subregions only in amyloid‐positive participants (Figure 1).ConclusionUntreated SDB has been previously associated with increased amyloid deposition, even in the absence of cognitive or sleep symptoms. Our data complement these findings by showing that once amyloid deposition reaches positivity, greater SDB severity is related to neurodegeneration in several MTL subregions, including the entorhinal cortex and hippocampus. Thus, the presence of SDB in cognitively unimpaired older adults who are engaged in the Alzheimer’s continuum may increase the risk of developing memory impairment over time.