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Biological brain age prediction using machine learning on structural neuroimaging data: multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex

Cumplido-Mayoral I, García-Prat M, Operto G, Falcon C, Shekari M, Cacciaglia R, Milà-Alomà M, Lorenzini L, Ingala S, Meije Wink A, Mutsaerts HJMM, Minguillón C, Fauria K, Molinuevo JL, Haller S, Chetelat G, Waldman A, Schwarz AJ, Barkhof F, Suridjan I, Kollmorgen G, Bayfield A, Zetterberg H, Blennow K, Suárez-Calvet M, Vilaplana V, Gispert López JD

Resum

Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD and OASIS. Brain-age delta was associated with abnormal amyloid-b, more advanced stages (AT) of AD pathology and APOE-e4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury.

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Cumplido-Mayoral I, García-Prat M, Operto G, Falcon C, Shekari M, Cacciaglia R, Milà-Alomà M, Lorenzini L, Ingala S, Meije Wink A, Mutsaerts HJMM, Minguillón C, Fauria K, Molinuevo JL, Haller S, Chetelat G, Waldman A, Schwarz AJ, Barkhof F, Suridjan I, Kollmorgen G, Bayfield A, Zetterberg H, Blennow K, Suárez-Calvet M, Vilaplana V, Gispert López JD. Biological brain age prediction using machine learning on structural neuroimaging data: multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex. Elife. 2023 Apr 17;12:e81067. doi: 10.7554/eLife.81067. Epub ahead of print. PMID: 37067031.