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

Abstract

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.

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