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Sleep-disordered breathing in cognitively unimpaired amyloid-positive individuals may exacerbate neurodegeneration in medial temporal lobe subregions

Although sleep-disordered breathing (SDB) has been associated with amyloid deposition and an increase in the risk of dementia, the mechanism behind this occurrence has remained unclear.

Study: Association of Sleep-Disordered Breathing and Medial Temporal Lobe Atrophy in Cognitively Unimpaired Amyloid-Positive Older Adults. Image Credit: Pixel-Shot/

A new Neurology study investigated the link between SDB severity and the volume of medial temporal lobe (MTL) substructures. In addition, it also evaluated the association between SDB and MTL subregions volumes with episodic memory performance.


Sleep-disordered breathing (SDB) has been associated with recurrent upper airway collapse during sleep, commonly prevalent in older adults. In most cases, SDB is underdiagnosed. SDB-induced sleep fragmentation and hypoxia increase the risk of cognitive dementia and cognitive decline. Several studies have also indicated that SDB triggers neurodegeneration.

In older adults with SDB, a higher deposition of amyloid was found, particularly in posterior cortical regions. Over a period of time, SDB may exacerbate amyloid pathology and interact with Alzheimer's Disease (AD) pathology to hasten cognitive decline.

Cognitively healthy older adults with SDB exhibit significantly more amyloid deposition and gray matter (GM) volume. In addition, these groups of individuals exhibit increased metabolism in the precuneus and posterior cingulate cortex. In contrast to previous research, no GM loss was observed in the MTL, which typically influences episodic memory.

MTL is composed of multiple subregions, including the hippocampus that can be divided into Cornu Ammonis (CA1 to 3), subiculum (SUB) and dentate gyrus (DG), and the entorhinal, perirhinal, and parahippocampal cortices. MTL subregions are differentially affected by AD pathology in predementia stages. Based on animal studies, some MTL structures, such as the hippocampus and CA1, are vulnerable to hypoxia. To date, the association between SDB and MTL volume integrity in older populations is not well understood.

Even though SDB alone may not be adequate to cause significant atrophy in amyloid-negative individuals, SDB-related neurodegeneration may be evident only when amyloid deposition becomes significant. It is imperative to understand in which conditions SDB influences MTL atrophy, as it could be a modifiable risk factor for cognitive decline.

About the study

The current study hypothesized that SDB was linked with GM atrophy in regions that are early affected by Alzheimer's disease pathology, particularly in amyloid-positive participants. All participants recruited in this study were enrolled in the Age-Well randomized controlled trial (RCT) of the Medit-Ageing European project, sponsored by the French National Institute of Health and Medical Research (INSERM).

Cognitively unimpaired older adults whose age were over 65, without any history of chronic diseases, major neurological and psychiatric disorders, or were not under any medication that could interfere with cognition, were recruited in this study. At baseline, participants were subjected to various examinations, such as neuropsychological assessment, polysomnography recording, structural magnetic resonance imaging (MRI), Apolipoprotein E e4 (ApoE4) genotyping and18F-Florbetapir positron emission tomography (PET) scan. All these tests were performed within approximately 32.24 days.

Participants were randomly assigned to three groups after baseline, namely, meditation-based intervention, foreign language training, and passive control arm. After eighteen months of interventions, participants underwent all assessments that were conducted at baseline.

Study findings

A total of 122 participants were selected for this study, of which 63.12% were women. The mean age of the participants was 69 years. Around 21% of the cohort were amyloid-positive, relatively older, and more susceptible to being ApoE4 carriers. However, these candidates did not exhibit altered memory performance, education level, MTL subregion volumes, or sleep data.

This study reveals that SDB severity can be determined through a higher apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). In addition, these parameters were linked with decreased GM volume in the entorhinal cortex and hippocampus in amyloid-positive individuals. Hippocampal subfields involved with these associations included CA1 and subiculum. A reduced CA1 and hippocampal volumes at baseline indicated poorer episodic memory performance at follow-up.

Based on the findings of complementary analyses, the links between SDB and GM atrophy were mostly bilateral and were restricted to temporal cortical areas. Women were also found to be more susceptible to the adverse effects of sleep apnea on the MTL. This study demonstrated that MTL subregions (e.g., entorhinal cortex-ERC and hippocampus) are particularly vulnerable to SDB. This finding can be linked to the observation that in the early phase of AD, ERC is affected, even before CA1 and subiculum subfields.

A recent human post-mortem study revealed that a higher SDB severity was associated with cortical thinning in the dentate gyrus, CA1, and ERC10. Some individuals were found to be at a higher risk of adverse effects of sleep apnea. Participants who were amyloid-positive were particularly vulnerable to SDB. There was no association between SDB and MTL integrity found in amyloid-negative participants.


The current study speculated that SDB may exacerbate Alzheimer's disease pathology in all participants. However, there is a decreased risk of SDB in amyloid-negative individuals. Compared to amyloid-positive individuals, amyloid-negative participants were more resilient to the adverse effects of SDB.

Taken together, SDB in cognitively unimpaired amyloid-positive individuals may enhance neurodegeneration in MTL subregions, which could lead to memory decline. More research is required to assess the benefits of SDB treatment.

Journal reference:
  • André, C. et al. (2023) "Association of Sleep-Disordered Breathing and Medial Temporal Lobe Atrophy in Cognitively Unimpaired Amyloid-Positive Older Adults", Neurology, pp. 10.1212/WNL.0000000000207421. doi: 10.1212/wnl.0000000000207421.

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Alzheimer's Disease, Apolipoprotein, Breathing, Chronic, Cortex, Dementia, Education, Genotyping, Hippocampus, Hypoxia, Imaging, Language, Magnetic Resonance Imaging, Medical Research, Meditation, Metabolism, Neurodegeneration, Neurology, Oxygen, Pathology, Positron Emission Tomography, Research, Sleep, Sleep Apnea, Tomography

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Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

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