Water exchange across blood‐brain barrier is associated with CSF amyloid‐42 level in healthy older adults
Year: 2020
Type: article
Study design: Observational Study
Abstract: Background The purpose of this study was to identify the association between a neuroimaging measure of brain water permeability and Alzheimer’s biomarkers in healthy older adults. Method Thirty‐nine older adults (20 female, age=72.7±5.3 yrs) without neurological disease underwent MRI on a Siemens 3T Prisma Fit system (Erlangen, Germany) using a 64‐channel head coil. The MR pulse sequence was a diffusion prepared 3D GRASE pCASL that has been detailed previously. The CSF samples were collected by lumbar draw within 6 months of MRI scan and quantification of CSF levels of A42, tau, and p‐tau was performed. Standard neuropsychological (NP) testing was performed on 37 of the participants to evaluate the cognitive performance. CBF/ATT/kw maps were normalized into the MNI space, and regional analysis was performed on the whole brain and in the frontal/temporal/parietal lobe, and subcortical regions including hippocampus, parahippocampal gyrus, anterior/posterior cingulate cortex (ACC/PCC), precuneus, caudate and putamen. Separate linear regression analyses were run with regional kw, CBF or ATT values as the independent variable and either CSF values or NP scores as the dependent variable and age and gender as covariates. Result Significant associations were found between A42 and kw in the whole brain (beta=0.43, t=3.2, p=0.012) and frontal lobe (beta=0.43, 2.7=, p=0.013), after controlling for age and sex. The associations between kw and A42 were also significant in the precuneus (beta=0.46, t=3.1, p= 0.004), parietal (beta=0.56, t=3.9, p < 0.001) and temporal lobe (beta=0.42, t=2.6, p = 0.015. No significant association was found between kw and CSF tau or p‐tau levels. A significant positive correlation was found between digit symbol substitution test (DSST) and kw in frontal lobe (beta=0.38, t=2.3, p=0.028). Conclusion The significant associations between kw and CSF A42 level and digit symbol in healthy older adult brains suggests kw may serve as an early imaging marker of AD.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.036794
Authors: Brian T Gold, Xingfeng Shao, Danny JJ Wang
Institutions: University of Kentucky, University of Southern California
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3111256036