Is Obstructive Sleep Apnea Severity Associated with Amyloid Beta Plaque in Brain Hippocampus?

by | Jan 12, 2021 | 2020, Alzheimer's Disease, Brain Health, Sleep

Written by Joyce Smith, BS. Study finds that amyloid beta (Aß) plaques in the hippocampus and brainstem of people with obstructive sleep apnea (OSA) does not correlate with OSA severity.

man sleepingOSA affects up to 30% of adults 1,2 and often leads to decreased attention, memory, and executive function 3. Yet, while continuous positive airway pressure (CPAP) may decrease symptoms in patients with milder OSA, there is concern that severe OSA may lead to permanent brain injury 4,5. People with OSA have 1.70 times (women) and 1.44 times (men) increased risk of developing dementia in the next 5 years 6,7. Alzheimer’s disease (AD) is the most common form of dementia, affecting up to 70% of all people with dementia, with age the biggest risk factor for developing the disease. OSA and AD can both lead to progressive deterioration of memory and executive dysfunction due to hippocampal brain atrophy 8,9 but while AD is characterized by an accumulation in the brain of Aß plaques and neurofibrillary tangles (NFTs), the presence of Aß plaques and NFTs in the brains of those with OSA has not yet been investigated.

In the current study 10, researchers examined autopsied brain tissue from Icelanders who were clinically diagnosed with OSA to determine whether OSA severity is associated with increasing deposits of Aß and neurofibrillary tangles (NFTs) in the brain. Autopsied tissue samples were obtained from the hippocampi of 34 subjects (18 females, 16 males, average age 67); 22 subjects provided both hippocampal and brainstem autopsy samples and a subset of 24 provided autopsy samples from only the brain stem.

In Alzheimer’s disease (AD), plaques and tangles first appear in a nearby cortical area and then move into the hippocampus, before spreading to the rest of the cortex 11. While the research team found both plaques and tangles in the brains of people with sleep apnea, the plaques showed a stronger association with severe sleep apnea. Those with mild sleep apnea had plaques and tangles only in the cortical area near the hippocampus where they originate in AD; yet, none had symptoms of cognitive impairment or undiagnosed dementia that were strong enough for an official AD diagnosis in spite of the presence of a high amount of plaques and tangles that could be qualified as AD.

All patients had OSA and 18 (52.9%) regularly used CPAP treatment prior to death. In the hippocampus biopsies, a significant positive correlation was seen between age and oxygen desaturation index (ODI) (P=0.014). CPAP users did not significantly differ from non-CPAP users by age, time from diagnosis to death, or ODI; however, CPAP users had a significantly higher mean BMI (P=0.002) and an insignificantly higher ODI (P=0.057). Of the 24 brain stem tissue samples, only 5 contained Aß plaques, prompting researchers to discontinue further investigation of brain stem pathology.

OSA severity was associated with greater Aβ but not with NFT in the hippocampus. However, in hippocampal tissue, age significantly predicted NFT (P =.002) while ODI significantly predicted Aβ after controlling for age, sex, BMI, and CPAP (P =.029). In analyses of patients who had samples from both the hippocampus and the brainstem, no significant relationship was found between the pathology in either brain region for tau (P =.065) or Aβ (P =.550).

The small Icelandic population in this study limits generalizability as well as statistical power. CPAP users had higher BMIs than non-CPAP users which may have confounded the relationship between CPAP use and the amount of NFTs and Aβ plaques. The use of a control group would have been beneficial. Larger clinical studies are warranted.

Source: Owen, Jessica E., Bryndis Benediktsdottir, Elizabeth Cook, Isleifur Olafsson, Thorarinn Gislason, and Stephen R. Robinson. “Alzheimer’s disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea.” Sleep (2020).

© Sleep Research Society 2020.

Posted January 12, 2021.

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. Gislason T, Sunnergren O. Obstructive sleep apnoea in adults. Respiratory Epidemiology (ERS Monograph). Sheffield, European Respiratory Society2014:88-105.
  2. 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.
  3. Buchanan PR, Grunstein RR. Positive-pressure treatment of obstructive sleep apnea syndrome. Handbook of Clinical Neurology. Vol 98: Elsevier; 2011:421-439.
  4. Torelli F, Moscufo N, Garreffa G, et al. Cognitive profile and brain morphological changes in obstructive sleep apnea. Neuroimage. 2011;54(2):787-793.
  5. Canessa N, Castronovo V, Cappa SF, et al. Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. Am J Respir Crit Care Med. 2011;183(10):1419-1426.
  6. Chang WP, Liu ME, Chang WC, et al. Sleep apnea and the risk of dementia: a population-based 5-year follow-up study in Taiwan. PLoS One. 2013;8(10):e78655.
  7. Ding X, Kryscio RJ, Turner J, et al. Self-Reported Sleep Apnea and Dementia Risk: Findings from the Prevention of Alzheimer’s Disease with Vitamin E and Selenium Trial. J Am Geriatr Soc. 2016;64(12):2472-2478.
  8. Rombouts SA, Barkhof F, Witter MP, Scheltens P. Unbiased whole-brain analysis of gray matter loss in Alzheimer’s disease. Neurosci Lett. 2000;285(3):231-233.
  9. Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2012;8(1):1-13.
  10. Owen JE, Benediktsdottir B, Cook E, Olafsson I, Gislason T, Robinson SR. Alzheimer’s disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea. Sleep. 2020.
  11. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta neuropathologica. 1991;82(4):239-259.