Cited by 41Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAdvanced Neuroimaging Techniques and Applications

Free water derived by multi‐shell diffusion MRI reflects tau/neuroinflammatory pathology in Alzheimer's disease

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Nakaya, Moto, Sato, Noriko, Matsuda, Hiroshi, Maikusa, Norihide, Shigemoto, Yoko, Sone, Daichi, Yamao, Tensho, Ogawa, Masayo +9 more·2022·Alzheimer's & Dementia: Translational Research & Clinical Interventions

Abstract

Introduction: Free‐water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET). Methods: Seventy‐one participants underwent multi‐shell diffusion MRI, 18 F‐THK5351 PET, 11 C‐Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) ( n = 40) and AD‐spectrum group (AD‐S) ( n = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores. Results: In AD‐S group, there was a significant positive correlation between FW and 18 F‐THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between 18 F‐THK5351 and cognitive function in the same regions. Discussion: FW imaging could be a biomarker for tau in AD alongside clinical correlations.

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  • White-matter free water has shown associations with cognitive performance and subsequent decline, particularly in limbic tracts.

    “White-matter free water has shown associations with cognitive performance and subsequent decline, particularly in limbic tracts (Nakaya et al., 2022; Peter et al., 2025).”

    From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Nakaya et al., 2022

    The Discussion (page not provided) reports an association between free water and cognitive performance, including a prior finding based on whole-brain white-matter regions. Nakaya et al.’s own cognitive correlations concern cortical regions, particularly the temporal lobe; the cited passages do not establish subsequent cognitive decline or an association particularly in limbic white-matter tracts. (LLM, conf=0.86)

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Research works printed but not linked: 2

  1. [25]Hoy AR, Koay CG, Kecskemeti SR, et al. Optimization of a free water elimination two‐compartmental model for diffusion tensor imaging. NeuroImage 2014; 103: 323‐ 333. 25271843 PMC4312191
  2. [59]Hoy AR, Ly M, Carlsson CM, et al. Microstructural white matter alterations in preclinical Alzheimer's disease detected using free water elimination diffusion tensor imaging. PLoS One. 2017; 12(3): e0173982. 28291839 PMC5349685

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Authors
Nakaya, M., Sato, N., Matsuda, H., Maikusa, N., Shigemoto, Y., Sone, D., Yamao, T., Ogawa, M., Kimura, Y., Chiba, E., Ohnishi, M., Kato, K., Okita, K., Tsukamoto, T., Yokoi, Y., Sakata, M., & Abe, O.
Affiliations
  • National Center of Neurology and Psychiatry (JP)
  • Jikei University School of Medicine (JP)
  • Fukushima Medical University (JP)
  • The University of Tokyo (JP)
Corresponding author
Sato, Noriko
Venue
Alzheimer's & Dementia: Translational Research & Clinical Interventions
Publisher
Wiley
Published
2022-01
Volume
8
Issue
1
Pages
e12356-e12356
ISSN
2352-8737 (ISSN-L)
OpenAlex
W4307581412
Cited by
41
References
58
Citations by year
2026: 8 · 2025: 18 · 2024: 10 · 2023: 4 · 2022: 1
FWCI
5.38
Type
journal article
Language
en
Open access
Locations
  • Alzheimer s & Dementia Translational Research & Clinical Interventions (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Japan Society for the Promotion of Science (20K08068)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Keywords
free-water imaging, Alzheimer's disease, tau pathology, neuroinflammation, amyloid PET, 18F-THK5351, Pittsburgh compound B, multi-shell diffusion MRI, cognitive function, temporal lobe, cingulate gyrus, biomarkers

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