Severe Obstructive Sleep Apnea and Increased Cortical Amyloid-β Deposition

J Alzheimers Dis. 2021;79(1):153-161. doi: 10.3233/JAD-200736.

Abstract

Background: The suggested association between severe obstructive sleep apnea (OSA) and risk of Alzheimer's disease (AD) needs further study. Only few recent reports exist on associations between brain amyloid-β (Aβ) burden and severe OSA in middle-aged patients.

Objective: Examine the possible presence of cortical Aβ accumulation in middle-aged patients with severe OSA.

Methods: We performed detailed multimodal neuroimaging in 19 cognitive intact patients (mean 44.2 years) with severe OSA (Apnea-Hypopnea Index >30 h-1). Known etiological factors for possible Aβ accumulation were used as exclusion criteria. Aβ uptake was studied with [11C]-PiB-PET, glucose metabolism with [18F]-FDG-PET, and structural imaging with 3.0T MRI.

Results: When analyzed individually, in [11C]-PiB-PET a substantial number (∼32%) of the patients exhibited statistically significant evidence of increased cortical Aβ uptake based on elevated regional Z-score values, mostly seen bilaterally in the precuneus and posterior cingulum regions. Cortical glucose hypometabolism in [18F]-FDG-PET was seen in two patients. MRI did not show structural changes suggestive of AD-related pathology.

Conclusion: Increased [11C]-PiB uptake was seen in middle-aged cognitively intact patients with severe OSA. These findings are similar to those described in cognitive unimpaired older OSA patients. The changes in cortical Aβ uptake suggest that severe OSA itself may predispose to alterations related to AD already in middle-age. Aβ clearance may be compromised without simultaneous evidence of metabolic or structural alterations. The results emphasize the importance of early diagnostics and proper treatment of severe OSA in cognitively intact middle-aged subjects, possibly diminishing the individual risk for later cognitive dysfunction.

Keywords: Alzheimer’s disease; PET; amyloid; sleep apnea.

MeSH terms

  • Adult
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / metabolism
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Radiopharmaceuticals
  • Severity of Illness Index
  • Sleep Apnea, Obstructive / diagnostic imaging*
  • Sleep Apnea, Obstructive / epidemiology
  • Sleep Apnea, Obstructive / metabolism
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Radiopharmaceuticals
  • Thiazoles
  • Fluorodeoxyglucose F18