White matter hyperintensities in cholinergic pathways may predict poorer responsiveness to acetylcholinesterase inhibitor treatment for Alzheimer's disease

PLoS One. 2023 Mar 31;18(3):e0283790. doi: 10.1371/journal.pone.0283790. eCollection 2023.

Abstract

Background: Acetylcholinesterase inhibitor (AChEI) drug regimens are the mainstay treatment options for patients with Alzheimer's disease (AD). Herein, We examined the association between clinical response to AChEI and white matter hyperintensities on magnetic resonance imaging (MRI) scan at baseline.

Methods: Between 2020 and 2021, we recruited 101 individuals with a clinical diagnosis of probable AD. Each participant underwent complete neuropsychological testing and 3T (Telsa) brain magnetic resonance imaging. Responsiveness to AChEI, as assessed after 12 months, was designated as less than two points of regression in Mini-Mental State Examination scores (MMSE) and stable clinical dementia rating scale. We also evaluated MRI images by examining scores on the Cholinergic Pathways Hyperintensities Scale (CHIPS), Fazekas scale, and medial temporal atrophy (MTA) scale.

Results: In our cohort, 52 patients (51.4%) were classified as responders. We observed significantly higher CHIPS scores in the nonresponder group (21.1 ± 12.9 vs. 14.9 ± 9.2, P = 0.007). Age at baseline, education level, sex, Clinical Dementia Rating sum of boxes scores, and three neuroimaging parameters were tested in regression models. Only CHIPS scores predicted clinical response to AChEI treatment.

Conclusion: WMHs in the cholinergic pathways, not diffuse white matter lesions or hippocampal atrophy, correlated with poorer responsiveness to AChEI treatment. Therefore, further investigation into the role of the cholinergic pathway in AD is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / drug therapy
  • Atrophy / pathology
  • Cholinergic Agents
  • Cholinesterase Inhibitors / therapeutic use
  • Humans
  • Magnetic Resonance Imaging / methods
  • Neuropsychological Tests
  • White Matter* / diagnostic imaging
  • White Matter* / pathology

Substances

  • Cholinesterase Inhibitors
  • Acetylcholinesterase
  • Cholinergic Agents

Grants and funding

The funding of this project was awarded to Yi-Chien Liu and came from Ministry of Science and Technology of Taiwan (MOST 108-2314-B-567-003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.