Obstructive Sleep Apnea is Associated With Early but Possibly Modifiable Alzheimer's Disease Biomarkers Changes

Sleep. 2017 May 1;40(5). doi: 10.1093/sleep/zsx011.


Study objectives: Obstructive sleep apnea (OSA) is a common sleep disorder. The, literature lacks studies examining sleep, cognition, and Alzheimer's Disease (AD) cerebrospinal fluid (CSF) biomarkers in OSA patients. Therefore, we first studied cognitive performances, polysomnographic sleep, and CSF β-amyloid42, tau proteins, and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea-Hypopnea Index [AHI] ≥15/hr), controls (showing an AHI < 15/hr), and patients with OSA treated by continuous positive airway pressure (CPAP).

Methods: We compared results among 25 OSA, 10 OSA-CPAP, and 15 controls who underwent a protocol counting neuropsychological testing in the morning, 48-hr polysomnography followed by CSF analysis.

Results: OSA patients showed lower CSF Aβ42 concentrations, higher CSF lactate levels, and higher t-tau/Aβ42 ratio compared to controls and OSA-CPAP patients. OSA patients also showed reduced sleep quality and continuity and lower performances at memory, intelligence, and executive tests than controls and OSA-CPAP patients. We found significant relationships among higher CSF tau proteins levels, sleep impairment, and increased CSF lactate levels in the OSA group. Moreover, lower CSF Aβ42 levels correlate with memory impairment and nocturnal oxygen saturation parameters in OSA patients.

Conclusions: We hypothesize that OSA reducing sleep quality and producing intermittent hypoxia lowers CSF Aβ42 levels, increases CSF lactate levels, and alters cognitive performances in SCI patients, thus inducing early AD clinical and neuropathological biomarkers changes. Notably, controls as well as OSA-CPAP SCI patients did not show clinical and biochemical AD markers. Therefore, OSA may induce early but possibly CPAP-modifiable AD biomarkers changes.

Keywords: continuous positive airway pressure; lactate; obstructive sleep apnea; subjective cognitive decline.; β-amyloid.

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / complications*
  • Alzheimer Disease / prevention & control
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid*
  • Cognition
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / prevention & control
  • Cognitive Dysfunction / therapy
  • Continuous Positive Airway Pressure*
  • Early Diagnosis
  • Early Medical Intervention*
  • Female
  • Humans
  • Intelligence
  • Lactic Acid / cerebrospinal fluid
  • Male
  • Memory
  • Memory Disorders / cerebrospinal fluid
  • Memory Disorders / complications
  • Memory Disorders / prevention & control
  • Memory Disorders / therapy
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • Polysomnography
  • Sleep
  • Sleep Apnea, Obstructive / cerebrospinal fluid
  • Sleep Apnea, Obstructive / complications*
  • Sleep Apnea, Obstructive / physiopathology
  • Sleep Apnea, Obstructive / therapy*
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Lactic Acid