White Matter Hyperintensity Load is Associated with Premature Brain Aging

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2022 Dec 1

PMID 36455869

Authors

Natalie Busby

Sarah Newman-Norlund

Sara Sayers

Roger Newman-Norlund

Sarah Wilson

Samaneh Nemati

Chris Rorden

Janina Wilmskoetter

Nicholas Riccardi

Rebecca Roth

Julius Fridriksson

Leonardo Bonilha

Affiliations

Soon will be listed here.

Abstract

Background: Brain age is an MRI-derived estimate of brain tissue loss that has a similar pattern to aging-related atrophy. White matter hyperintensities (WMHs) are neuroimaging markers of small vessel disease and may represent subtle signs of brain compromise. We tested the hypothesis that WMHs are independently associated with premature brain age in an original aging cohort.

Methods: Brain age was calculated using machine-learning on whole-brain tissue estimates from T1-weighted images using the BrainAgeR analysis pipeline in 166 healthy adult participants. WMHs were manually delineated on FLAIR images. WMH load was defined as the cumulative volume of WMHs. A positive difference between estimated brain age and chronological age (BrainGAP) was used as a measure of premature brain aging. Then, partial Pearson correlations between BrainGAP and volume of WMHs were calculated (accounting for chronological age).

Results: Brain and chronological age were strongly correlated ((163)=0.932, <0.001). There was significant negative correlation between BrainGAP scores and chronological age ((163)=-0.244, <0.001) indicating that younger participants had higher BrainGAP (premature brain aging). Chronological age also showed a positive correlation with WMH load ((163)=0.506, <0.001) indicating older participants had increased WMH load. Controlling for chronological age, there was a statistically significant relationship between premature brain aging and WMHs load ((163)=0.216, =0.003). Each additional year in brain age beyond chronological age corresponded to an additional 1.1mm in WMH load.

Conclusions: WMHs are an independent factor associated with premature brain aging. This finding underscores the impact of white matter disease on global brain integrity and progressive age-like brain atrophy.

Citing Articles

Markers of Biological Brain Aging Mediate Effects of Vascular Risk Factors on Cognitive and Motor Functions: A Multivariate Imaging Analysis of 40,579 Individuals.

Petersen M, Link M, Mayer C, Nagele F, Schell M, Fiehler J medRxiv. 2024; .

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Longitudinal Progression of White Matter Hyperintensity Severity in Chronic Stroke Aphasia.

Busby N, Newman-Norlund R, Wilmskoetter J, Johnson L, Rorden C, Gibson M Arch Rehabil Res Clin Transl. 2024; 5(4):100302.

PMID: 38163020 PMC: 10757197. DOI: 10.1016/j.arrct.2023.100302.

Dynamic network properties of the superior temporal gyrus mediate the impact of brain age gap on chronic aphasia severity.

Wilmskoetter J, Busby N, He X, Caciagli L, Roth R, Kristinsson S Commun Biol. 2023; 6(1):727.

PMID: 37452209 PMC: 10349039. DOI: 10.1038/s42003-023-05119-z.

Neuroimaging and machine learning for brain age estimation.

Kocar T, Denkinger M, Kassubek J Aging (Albany NY). 2023; 15(8):2822-2823.

PMID: 37116194 PMC: 10188341. DOI: 10.18632/aging.204694.

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