- Habes, Mohamad;
- Pomponio, Raymond;
- Shou, Haochang;
- Doshi, Jimit;
- Mamourian, Elizabeth;
- Erus, Guray;
- Nasrallah, Ilya;
- Launer, Lenore J;
- Rashid, Tanweer;
- Bilgel, Murat;
- Fan, Yong;
- Toledo, Jon B;
- Yaffe, Kristine;
- Sotiras, Aristeidis;
- Srinivasan, Dhivya;
- Espeland, Mark;
- Masters, Colin;
- Maruff, Paul;
- Fripp, Jurgen;
- Völzk, Henry;
- Johnson, Sterling C;
- Morris, John C;
- Albert, Marilyn S;
- Miller, Michael I;
- Bryan, R Nick;
- Grabe, Hans J;
- Resnick, Susan M;
- Wolk, David A;
- Davatzikos, Christos;
- for the iSTAGING consortium, the Preclinical AD consortium
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.