Impaired Glymphatic Flow on Diffusion Tensor MRI as a Marker of Neurodegeneration in Alzheimer's Disease: Correlation with Gray Matter Volume Loss and Cognitive Decline Independent of Cerebral Amyloid Deposition

J Alzheimers Dis. 2024;99(1):279-290. doi: 10.3233/JAD-231131.

Abstract

Background: Impaired glymphatic flow on the Alzheimer's disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS).

Objective: We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum.

Methods: 80 participants (mean age, 76.9±8.5 years; 57 women) with AD (n = 65) and cognitively normal (CN) (n = 15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed.

Results: The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395-1.556) than in the CN (1.784;1.615-1.952; p = 0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, p < 0.05). There was a positive correlation between the ALPS-index and MMSE score (partial r = 0.435; p < 0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, p > 0.05).

Conclusions: Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline.

Keywords: Alzheimer’s disease; amyloid PET; diffusion tensor; glymphatic function; volumetry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / pathology
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / metabolism
  • Cognitive Dysfunction* / pathology
  • Diffusion Tensor Imaging*
  • Female
  • Glymphatic System* / diagnostic imaging
  • Glymphatic System* / metabolism
  • Glymphatic System* / pathology
  • Gray Matter* / diagnostic imaging
  • Gray Matter* / metabolism
  • Gray Matter* / pathology
  • Humans
  • Male
  • Positron-Emission Tomography*