17 Apr 23. Featured Paper

Link to paper in eLife

Authors

Cumplido-Mayoral I, García-Prat M, Operto G, Falcon C, Shekari M, Cacciaglia R, Milà-Alomà M, Lorenzini L, Ingala S, Wink AM, 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 JD, ALFA study, EPAD study, ADNI study, OASIS study

Abstract

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-β, more advanced stages (AT) of AD pathology and APOE-ε4 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.

Keywords

• Alzheimer’s disease (AD)
• Brain age
• Neurodegeneration
• Mild cognitive impairment (MCI)
• Amyloid-β
• APOE-ε4