4.5 Article

Associations of increased interstitial fluid with vascular and neurodegenerative abnormalities in a memory clinic sample

Journal

NEUROBIOLOGY OF AGING
Volume 106, Issue -, Pages 257-267

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2021.06.017

Keywords

Alzheimer's disease; Interstitial fluid; Intravoxel incoherent motion; Spectral analysis; Glymphatic system

Funding

  1. Alzheimer Nederland [WE.03-2018-13, WE.03-2012-40, WE.03-2018-02, WE.09-2019-02]
  2. NIH-NIA [R01AG06255]
  3. Siemens Healthcare
  4. Bayer Healthcare
  5. Stichting 2bike4alzheimer

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In memory clinic patients, a large interstitial fluid volume is associated with both neurodegenerative abnormalities and vascular pathology, potentially playing a role in impaired glymphatic functioning.
The vascular and neurodegenerative processes related to clinical dementia cause cell loss which induces, amongst others, an increase in interstitial fluid (ISF). We assessed microvascular, parenchymal integrity, and a proxy of ISF volume alterations with intravoxel incoherent motion imaging in 21 healthy controls and 53 memory clinic patients - mainly affected by neurodegeneration (mild cognitive impairment, Alzheimer's disease dementia), vascular pathology (vascular cognitive impairment), and presumed to be without significant pathology (subjective cognitive decline). The microstructural components were quantified with spectral analysis using a non-negative least squares method. Linear regression was employed to investigate associations of these components with hippocampal and white matter hyperintensity (WMH) volumes. In the normal appearing white matter, a large f(int )(a proxy of ISF volume) was associated with a large WMH volume and low hippocampal volume. Likewise, a large f(int) value was associated with a lower hippocampal volume in the hippocampi. Large ISF volume (f(int)) was shown to be a prominent factor associated with both WMHs and neurodegenerative abnormalities in memory clinic patients and is argued to play a potential role in impaired glymphatic functioning. (C) 2021 The Author(s). Published by Elsevier Inc.

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