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Van Waalwijk van Doorn et al_WMH_JAD_accepted manuscript - White matter hyperintensities ....pdf (1.03 MB)

White matter hyperintensities are no major confounder for alzheimer's disease cerebrospinal fluid biomarkers

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posted on 2023-06-09, 22:27 authored by Linda J C van Waalwijk van Doorn, Mohsen Ghafoorian, Esther M C van Leijsen, Jurgen A H R Claassen, Andrea Arighi, Marco Bozzali, Jorge Cannas, Enrica Cavedo, Paolo Eusebi, Lucia Farotti, Chiara Fenoglio, Juan Fortea, Giovanni B Frisoni, Daniela Galimberti, Viviana Greco, others
Background: The cerebrospinal fluid (CSF) biomarkers amyloid-ß 1–42 (Aß 42), total and phosphorylated tau (t-tau, p-tau) are increasingly used to assist in the clinical diagnosis of Alzheimer’s disease (AD). However, CSF biomarker levels can be affected by confounding factors. Objective: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. Methods: We included CSF biomarker and magnetic resonance imaging (MRI) data of 172 subjects (52 controls, 72 mild cognitive impairment (MCI), and 48 AD patients) from 9 European Memory Clinics. A computer aided detection system for standardized automated segmentation of WMHs was used on MRI scans to determine WMH volumes. Association of WMH volume with AD CSF biomarkers was determined using linear regression analysis. Results: A small, negative association of CSF Aß 42, but not p-tau and t-tau, levels with WMH volume was observed in the AD (r 2?=?0.084, p?=?0.046), but not the MCI and control groups, which was slightly increased when including the distance of WMHs to the ventricles in the analysis (r 2?=?0.105, p?=?0.025). Three global patterns of WMH distribution, either with 1) a low, 2) a peak close to the ventricles, or 3) a high, broadly-distributed WMH volume could be observed in brains of subjects in each diagnostic group. Conclusion: Despite an association of WMH volume with CSF Aß 42 levels in AD patients, the occurrence of WMHs is not accompanied by excess release of cellular proteins in the CSF, suggesting that WMHs are no major confounder for AD CSF biomarker assessment.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Journal of Alzheimer's Disease

ISSN

1387-2877

Publisher

IOS Press

Page range

1-13

Event location

Netherlands

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2020-12-15

First Open Access (FOA) Date

2020-12-15

First Compliant Deposit (FCD) Date

2020-12-15

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