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Brain clocks capture diversity and disparity in aging and dementia.

Sebastian MoguilnerSandra BaezHernan HernandezJoaquín MigeotAgustina LegazRaul Gonzalez-GomezFrancesca R FarinaPavel Prado-GutierrezJhosmary CuadrosEnzo TagliazucchiFlorencia AltschulerMarcelo Adrián MaitoMaría E GodoyJosephine CruzatPedro A Valdes-SosaFrancisco LoperaJohn Fredy Ochoa-GómezAlfredis Gonzalez HernandezJasmin Bonilla-SantosRodrigo A Gonzalez-MontealegreRenato AnghinahLuís E d'Almeida ManfrinatiSol FittipaldiVicente MedelDaniela OlivaresGörsev G YenerJavier EscuderoClaudio BabiloniRobert WhelanBahar GüntekinHarun YırıkoğullarıHernando Santamaria-GarciaAlberto Fernández LucasDavid HuepeGaetano Di CaterinaMarcio Soto-AñariAgustina BirbaAgustin Sainz-BallesterosCarlos Coronel-OliverosAmanuel YigezuEduar HerreraDaniel AbasoloKerry KilbornNicolás RubidoRuaridh A ClarkRubén HerzogDeniz YerlikayaKun HuMario A ParraPablo ReyesAdolfo M GarcíaDiana L MatallanaJosé Alberto Avila-FunesAndrea SlachevskyMaría I BehrensNilton CustodioJuan F CardonaPablo BarttfeldIgnacio L BruscoMartín A BrunoAna L Sosa OrtizStefanie D Pina-EscuderoLeonel Tadao TakadaElisa ResendeKatherine L PossinMaira Okada de OliveiraAlejandro Lopez-ValdesBrain LawlorIan H RobertsonKenneth S KosikClaudia Duran-AniotzVictor ValcourJennifer S YokoyamaBruce L MillerAgustin M Ibanez
Published in: Research square (2024)
Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R 2 =0.37, F 2 =0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging.
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