Gray matter reserve determines glymphatic system function in young-onset Alzheimer's disease: Evidenced by DTI-ALPS and compared with age-matched controls

Hsin I. Chang, Chi Wei Huang, Shih Wei Hsu, Shu Hua Huang, Kun Ju Lin, Tsung Ying Ho, Mi Chia Ma, Wen Chiu Hsiao, Chiung Chih Chang

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: The diffusion tensor imaging analysis along the perivascular space (ALPS)-index can be used to model the glymphatic system in vivo. Aim: This study explores putative mechanisms between prediction of ALPS-index and cognitive outcomes in young-onset Alzheimer's disease (YOAD) and age-matched controls (CTLs) and analyzes whether the link was mediated by the integrity of ALPS-index-anchored cerebral gray matter (GM). Methods: We enrolled 130 patients with YOAD and 137 CTLs. All participants underwent three-dimensional T1-weighted MRI, diffusion tensor imaging and cognitive tests. We constructed GM regions correlated with the ALPS-index in the YOAD and CTL groups. For the GM regions significantly correlated with the ALPS-index and cognitive measures, we extracted a 4-mm radius sphere. In the YOAD and CTL groups, we used mediator analysis to explore the ALPS-index as predictor, GM partitions as mediators, and significant cognitive test scores as outcomes. Results: Patient group had significantly lower ALPS-index. The ALPS-index was associated with GM volume in the cerebellar gray, dorsolateral prefrontal, thalamus, superior frontal, amygdala and hippocampus, and these coherent regions coincided with those showing GM atrophy in the YOAD group. Mediation analysis of the YOAD group suggested that the relationships between the ALPS-index and cognitive performance were fully mediated by the integrity of ALPS-index coherent GM areas. Discussion: Reserved GM mediates the link between the glymphatic system and cognition. Our findings suggest that GM integrity rather than the glymphatic system could serve as a direct cognitive test scores predictor in patients with YOAD.

Original languageEnglish
Pages (from-to)401-409
Number of pages9
JournalPsychiatry and Clinical Neurosciences
Volume77
Issue number7
DOIs
Publication statusPublished - 2023 Jul

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

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