Machine learning reveals distinct neuroanatomical signatures of cardiovascular and metabolic diseases in cognitively unimpaired individuals
Abstract
Abstract Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45–85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect sizes, ii) captured subtle patterns at sub-clinical CVM stages, iii) were most sensitive in mid-life (45–64 years), iv) were associated with brain beta-amyloid status, and v) showed stronger associations with cognitive performance than diagnostic CVM status. Integrating personalized measurements of CVM-specific brain signatures into phenotypic frameworks could guide early risk detection and stratification in clinical studies.
Article Details
Authors (29)
Sindhuja Tirumalai Govindarajan
Elizabeth Mamourian
Guray Erus
Ahmed Abdulkadir
Randa Melhem
Jimit Doshi
Raymond Pomponio
Duygu Tosun
Murat Bilgel
Yang An
Aristeidis Sotiras
Daniel S. Marcus
Pamela LaMontagne
Tammie L. S. Benzinger
Mark A. Espeland
Colin L. Masters
Paul Maruff
Lenore J. Launer
Jurgen Fripp
Sterling C. Johnson
John C. Morris
Marilyn S. Albert
R. Nick Bryan
Susan M. Resnick
Mohamad Habes
Haochang Shou
David A. Wolk
Ilya M. Nasrallah
Christos Davatzikos