Sleep-Disordered Breathing Associated with Alzheimer Disease in Asymptomatic Elderly

by | Apr 20, 2020 | 2020, Alzheimer's Disease, Brain Health, Respiratory Health, Sleep

Written by Joyce Smith, BS. Study found that cognitively unimpaired older adults with sleep-disordered breathing (SDB) had SDB-associated brain changes, including greater amyloid deposition and neuronal activity in brain regions associated with Alzheimer disease.

sleepSDB, a respiratory disorder affecting 30 -80% of cognitively unimpaired adults 1, is characterized by recurrent upper airway collapse during sleep and associated with intermittent hypoxia and fragmented sleep 2. Clinically diagnosed Alzheimer’s patients are even more susceptible to SDB, and when left untreated, SDB has been associated with cognitive decline and shown to convert to Alzheimer clinical syndrome at a younger age 3. Studies attempting to clarify the brain changes associated with SDB have documented inconsistent results 4,5.

André and colleagues conducted a cross-sectional study 6 using data acquired between 2016 and 2018 on 157 patients from the Age-Well randomized clinical trial of the Medit-Ageing European project at Cyceron Center in Caen, France. Their objective was to determine which brain changes are associated with the presence of SDB in a cohort of 127 untreated cognitively unimpaired patients (mean age, 69.1 years; 60 % women) who had few self-reported sleep difficulties. Participants were diagnosed with SDB based on an apnea-hypopnea index cutoff of 15 events per hour.

Researchers used multimodaling neuroimaging to detect early structural, functional and molecular changes within the brain that suggested a potential link to SDB and to identify which aspects of SDB (sleep fragmentation, hypoxia severity, or frequency of respiratory events) might be associated with observable brain changes such as changes in amyloid deposition, gray matter volume, perfusion, and glucose metabolism.  Lastly, they sought to explore potential associations between SDB severity and cognitive performance, self-reported cognitive and sleep difficulties and symptoms of sleepiness.

The team found that participants with SDB demonstrated greater amyloid deposition (P=0.04), greater GM volume, greater metabolism, and greater perfusion within the parieto-occipital regions of the brain, including the precuneus and posterior cingulate cortex. They also found that the increased amyloid deposits were strongly associated with the severity of hypoxia (the amount of oxygen reaching tissues). Neither the severity of SDB nor the SDB-associated brain changes were associated with cognitive performance, self-reported cognitive and sleep difficulties, and symptoms of excessive daytime sleepiness.

Researchers suggest that these SDB-associated changes, which included the deposition of amyloid in brain regions typically involved in Alzheimer’s disease (namely the posterior cingulate cortex and the precuneus), may explain why SDB is associated with an increased risk of developing Alzheimer clinical syndrome at a younger age.

Study limitations include its cross-sectional design, which did not allow for the evaluation of a causal relationship between brain changes and SDB. Longitudinal studies are recommended to explore whether early SDB-associated brain changes will progress to neurodegeneration and cognitive deficits.

Source: André, Claire, Stéphane Rehel, Elizabeth Kuhn, Brigitte Landeau, Inès Moulinet, Edelweiss Touron, Valentin Ourry et al. “Association of Sleep-Disordered Breathing With Alzheimer Disease Biomarkers in Community-Dwelling Older Adults: A Secondary Analysis of a Randomized Clinical Trial.” JAMA neurology (2020).

© 2020 American Medical Association. All rights reserved.

Posted April 20, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Senaratna CV, Perret JL, Lodge CJ, et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev. 2017;34:70-81.
  2. Malhotra A, White DP. Obstructive sleep apnoea. The lancet. 2002;360(9328):237-245.
  3. Leng Y, McEvoy CT, Allen IE, Yaffe K. Association of Sleep-Disordered Breathing With Cognitive Function and Risk of Cognitive Impairment: A Systematic Review and Meta-analysis. JAMA Neurol. 2017;74(10):1237-1245.
  4. Osorio RS, Ayappa I, Mantua J, et al. Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer’s disease in cognitively normal elderly individuals. Neurobiol Aging. 2014;35(6):1318-1324.
  5. Sharma RA, Varga AW, Bubu OM, et al. Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study. Am J Respir Crit Care Med. 2018;197(7):933-943.
  6. André C, Rehel S, Kuhn E, et al. Association of Sleep-Disordered Breathing With Alzheimer Disease Biomarkers in Community-Dwelling Older Adults: A Secondary Analysis of a Randomized Clinical Trial. JAMA Neurol. 2020.