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Area of Science:

  • Neuroscience
  • Sleep Medicine
  • Biomarkers of Alzheimer's Disease

Background:

  • Alzheimer's disease (AD) is associated with sleep disturbances and altered slow wave activity (SWA).
  • These sleep changes may be linked to amyloid (A) β and tau pathology, potentially via glymphatic system (GS) dysfunction.
  • Evaluating SWA and GS integrity across the AD continuum is crucial for understanding disease progression.

Purpose of the Study:

  • To investigate alterations in SWA and GS function across different stages of the Alzheimer's disease continuum.
  • To examine the relationship between SWA, GS integrity, and amyloid pathology in cognitively unimpaired (CU) individuals and early AD (eAD) patients.

Main Methods:

  • Video-polysomnography (PSG) was used to measure sleep parameters, including SWA, in 116 participants (30 CU A-, 45 CU A+, 41 eAD).
  • Amyloid status was determined using CSF Aβ42/40 ratio or Aβ PET imaging.
  • Diffusion tensor image analysis along the perivascular space (DTI-ALPS) was employed to assess GS function in CU participants.

Main Results:

  • Early AD patients exhibited poorer sleep efficiency and longer wake after sleep onset and REM latency compared to controls.
  • Both amyloid-positive (A+) cognitively unimpaired individuals and eAD patients showed reduced slow oscillation (SO), delta, and SWA power compared to amyloid-negative (A-) individuals.
  • In cognitively unimpaired individuals, DTI-ALPS was positively associated with delta and SWA power, suggesting a link between GS function and sleep activity.

Conclusions:

  • Alzheimer's disease progression is characterized by significant alterations in SWA.
  • Impaired glymphatic system function may contribute to SWA changes and promote amyloid-beta accumulation in AD.
  • These findings highlight the interplay between sleep, glymphatic function, and AD pathology.