The Brain Chart of Aging: Machine-learning analytics reveals links between brain aging, white matter disease, amyloid burden, and cognition in the iSTAGING consortium of 10,216 harmonized MR scans

Published in Alzheimer's and Dementia, 2021

Mohamad Habes, Raymond Pomponio, Haochang Shou, Jimit Doshi, Elizabeth Mamourian, Guray Erus, Ilya Nasrallah, Lenore Launer, Tanweer Rashid, Murat Bilgel, Yong Fan, Jon Toledo, Kristine Yaffe, Aristeidis Sotiras, Dhivya Srinivasan, Mark Espeland, Colin Masters, Paul Maruff, Jurgen Fripp, Henry Völzk, Sterling Johnson, John Morris, Marilyn Albert, Michael Miller, R Bryan, Hans Grabe, Susan Resnick, David Wolk, Christos Davatzikos, "The Brain Chart of Aging: Machine-learning analytics reveals links between brain aging, white matter disease, amyloid burden, and cognition in the iSTAGING consortium of 10,216 harmonized MR scans." Alzheimer’s & and Dementia, 2021.


Abstract

Introduction: Relationships between brain atrophy patterns of typical aging and Alzheimer’s disease (AD), white matter disease, cognition, and AD neuropathology were investigated via machine learning in a large harmonized magnetic resonance imaging database (11 studies; 10,216 subjects).

Methods: Three brain signatures were calculated: Brain-age, AD-like neurodegeneration, and white matter hyperintensities (WMHs). Brain Charts measured and displayed the relationships of these signatures to cognition and molecular biomarkers of AD.

Results: WMHs were associated with advanced brain aging, AD-like atrophy, poorer cognition, and AD neuropathology in mild cognitive impairment (MCI)/AD and cognitively normal (CN) subjects. High WMH volume was associated with brain aging and cognitive decline occurring in an ≈10-year period in CN subjects. WMHs were associated with doubling the likelihood of amyloid beta (Aβ) positivity after age 65. Brain aging, AD-like atrophy, and WMHs were better predictors of cognition than chronological age in MCI/AD.

Discussion: A Brain Chart quantifying brain-aging trajectories was established, enabling the systematic evaluation of individuals’ brain-aging patterns relative to this large consortium.

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