Relationships between blood pressure indicators and fluid biomarkers of brain aging in functionally intact older adults

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Background : Dementia risk is significantly shaped by cardiovascular health, with elevated blood pressure emerging as a key factor for adverse brain aging. Blood biomarkers such pTau181, Aβ42/40, NfL, and GFAP have improved our understanding of dementia pathophysiology, however, few studies explored how specific metrics relate to biomarker levels, which could inform personalized prevention strategies these move into clinic. We examined different associated molecular markers astrocytic activation (GFAP), neuronal axon breakdown (NfL), Alzheimer's disease pathobiology (pTau181, Aβ42/40) in plasma. Methods 109 functionally intact (Clinical Rating Scale=0) older adults completed draws plasma assayed GFAP, pTau181 (Quanterix Simoa) in-lab quantification. included diastolic pressure, systolic pulse (systolic minus diastolic). Separate regression models evaluated function each metric, adjusting age biological sex. Interaction tested whether relationships between differed sex, age, or APOE -ε4 status. Results With the exception higher related levels all GFAP). Additionally, while did not meaningfully associate any biomarker. revealed stronger relationship concentrations females compared males, well association lower Aβ42/40 carriers non-carriers. Conclusions Our findings suggest that lesser extent are increased neurodegenerative (axonal health) biology among typically aging adults. These associations underscore importance management, particularly reducing risk. Cardiovascular health may be incorporated further personalize management strategies.

Язык: Английский

Brain Age Gap as a Predictive Biomarker: Linking Aging, Lifestyle, and Neuropsychiatric Health

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

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.

Язык: Английский

Relationships between blood pressure indicators and fluid biomarkers of brain aging in functionally intact older adults

Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 21, 2025

Abstract Background Dementia risk is significantly shaped by cardiovascular health, with elevated blood pressure emerging as a key factor for adverse brain aging. Blood biomarkers such pTau181, Aβ42/40, NfL, and GFAP have improved our understanding of dementia pathophysiology, however, few studies explored how specific metrics relate to biomarker levels, which could inform personalized prevention strategies these move into clinic. We examined different associated molecular markers astrocytic activation (GFAP), neuronal axon breakdown (NfL), Alzheimer’s disease pathobiology (pTau181, Aβ42/40) in plasma. Methods 109 functionally intact (Clinical Rating Scale = 0) older adults completed draws plasma assayed GFAP, pTau181 (Quanterix Simoa) in-lab quantification. included diastolic pressure, systolic pulse (systolic minus diastolic). Separate regression models evaluated function each metric, adjusting age biological sex. Interaction tested whether relationships between differed sex, age, or APOE -ε4 status. Results With the exception higher related levels all GFAP). Additionally, while did not meaningfully associate any biomarker. revealed stronger relationship concentrations females compared males, well association lower Aβ42/40 carriers non-carriers. Conclusions Our findings suggest that lesser extent are increased neurodegenerative (axonal health) biology among typically aging adults. These associations underscore importance management, particularly reducing risk. Cardiovascular health may be incorporated further personalize management strategies.

Язык: Английский