Brain Age Gap as a Predictive Biomarker: Linking Aging, Lifestyle, and Neuropsychiatric Health DOI
Zhengxing Huang, Ruixia Zhang,

Yi Fan

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Background The brain age gap (BAG), a neuroimaging-derived biomarker of accelerated aging, faces translational challenges due to model inaccuracies and unclear disease-mechanism linkages. We systematically evaluated BAG's clinical relevance across neuropsychiatric disorders, cognitive trajectories, mortality, lifestyle interventions. Methods Using multi-cohort data (UK Biobank [n = 38,967], Alzheimer’s Disease Neuroimaging Initiative [ADNI; n 1,402], Parkinson’s Progression Markers [PPMI; 1,182]), we developed 3D Vision Transformer (3D-ViT) for whole-brain estimation. Survival analyses, restricted cubic splines, stratified regressions assessed BAG’s associations with cognition, 16 mortality. Lifestyle modulation effects were quantified through longitudinal BAG progression. Results demonstrated robust predictive accuracy, achieving mean absolute error (MAE) 2.68 years in the UK cohort 2.99–3.20 external validation cohorts (ADNI/PPMI). Per 1-year increment was linearly associated elevated risks Alzheimer's disease (HR 1.165, 95% CI 1.086–1.249; +16.5% risk/year), mild impairment 1.040, 1.030–1.050; +4.0%), all-cause mortality 1.12, 1.09–1.15; +12%; all p < 0.001). Individuals highest quartile (Q4) faced substantially amplified risks: 2.8-fold 2.801), 6.4-fold multiple sclerosis 6.417), 1.5-fold major depressive disorder 1.466). Notably, prodromal Parkinson's exhibited paradoxical rejuvenation (mean Δ=−1.441 years, 0.001), contrasting nonsignificant incident cases 1.830, 0.154). Cognitive decline followed nonlinear critical thresholds domain-specific emerging at Q4 (BAG > 2.48 years). interventions synergistically attenuated progression advanced neurodegeneration (Q3–Q4; 0.05), particularly smoking cessation, moderated alcohol consumption, physical activity. Interpretation: robustly predicts multimorbidity, Its stage-dependent modifiability underscore utility risk stratification personalized prevention strategies.

Language: Английский

Brain Age Gap as a Predictive Biomarker: Linking Aging, Lifestyle, and Neuropsychiatric Health DOI
Zhengxing Huang, Ruixia Zhang,

Yi Fan

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Background The brain age gap (BAG), a neuroimaging-derived biomarker of accelerated aging, faces translational challenges due to model inaccuracies and unclear disease-mechanism linkages. We systematically evaluated BAG's clinical relevance across neuropsychiatric disorders, cognitive trajectories, mortality, lifestyle interventions. Methods Using multi-cohort data (UK Biobank [n = 38,967], Alzheimer’s Disease Neuroimaging Initiative [ADNI; n 1,402], Parkinson’s Progression Markers [PPMI; 1,182]), we developed 3D Vision Transformer (3D-ViT) for whole-brain estimation. Survival analyses, restricted cubic splines, stratified regressions assessed BAG’s associations with cognition, 16 mortality. Lifestyle modulation effects were quantified through longitudinal BAG progression. Results demonstrated robust predictive accuracy, achieving mean absolute error (MAE) 2.68 years in the UK cohort 2.99–3.20 external validation cohorts (ADNI/PPMI). Per 1-year increment was linearly associated elevated risks Alzheimer's disease (HR 1.165, 95% CI 1.086–1.249; +16.5% risk/year), mild impairment 1.040, 1.030–1.050; +4.0%), all-cause mortality 1.12, 1.09–1.15; +12%; all p < 0.001). Individuals highest quartile (Q4) faced substantially amplified risks: 2.8-fold 2.801), 6.4-fold multiple sclerosis 6.417), 1.5-fold major depressive disorder 1.466). Notably, prodromal Parkinson's exhibited paradoxical rejuvenation (mean Δ=−1.441 years, 0.001), contrasting nonsignificant incident cases 1.830, 0.154). Cognitive decline followed nonlinear critical thresholds domain-specific emerging at Q4 (BAG > 2.48 years). interventions synergistically attenuated progression advanced neurodegeneration (Q3–Q4; 0.05), particularly smoking cessation, moderated alcohol consumption, physical activity. Interpretation: robustly predicts multimorbidity, Its stage-dependent modifiability underscore utility risk stratification personalized prevention strategies.

Language: Английский

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