$\textbf{Objective:}$ Brain-predicted age difference (BrainAGE) is a neuroimaging biomarker reflecting brain health. However, training robust BrainAGE models requires large datasets, often restricted by privacy concerns. This study evaluates the performance of federated learning (FL) for BrainAGE estimation in ischemic stroke patients treated with mechanical thrombectomy, and investigates its association with clinical phenotypes and functional outcomes. $\textbf{Methods:}$ We used FLAIR brain images from 1674 stroke patients across 16 hospital centers. We implemented standard machine learning and deep learning models for BrainAGE estimates under three data management strategies: centralized learning (pooled data), FL (local training at each site), and single-site learning. We reported prediction errors and examined associations between BrainAGE and vascular risk factors (e.g., diabetes mellitus, hypertension, smoking), as well as functional outcomes at three months post-stroke. Logistic regression evaluated BrainAGE's predictive value for these outcomes, adjusting for age, sex, vascular risk factors, stroke severity, time between MRI and arterial puncture, prior intravenous thrombolysis, and recanalisation outcome. $\textbf{Results:}$ While centralized learning yielded the most accurate predictions, FL consistently outperformed single-site models. BrainAGE was significantly higher in patients with diabetes mellitus across all models. Comparisons between patients with good and poor functional outcomes, and multivariate predictions of these outcomes showed the significance of the association between BrainAGE and post-stroke recovery. $\textbf{Conclusion:}$ FL enables accurate age predictions without data centralization. The strong association between BrainAGE, vascular risk factors, and post-stroke recovery highlights its potential for prognostic modeling in stroke care.

Motivation: Brain aging varies significantly between sexes, yet genetic contributions to these differences remain under - explored. Goal: Identify sex - specific genetic variants linked to accelerated brain aging using structural MRI data. Approach: This study proposes implementing Brain Age Gap Estimates (BrainAGE) with sex - stratified GW AS to uncover genetic associations in T1 - weighted MRI data from the UK Biobank, complemented by Post - GW AS analyses to explore biological pathways and gene expression. Results: Sex - stratified analyses revealed neurotransmitter and mitochondrial response to cellular stress genes linked to brain aging in females and immune - related genes in males. Shared genes suggest common neurostructural roles, advancing understanding of sex - specific genetic determinants in brain aging. Impact: This study highlights the importance of sex - stratified analysis in understanding the genetic associations with brain aging. Findings pave the way for future work on personalized treatments and preventative measures for neurodegeneration based on individual genetic profiles and sex - specific risks.

The increasing global aging population necessitates improved methods to assess brain aging and its related neurodegenerative changes. Brain Age Gap Estimation (BrainAGE) offers a neuroimaging biomarker for understanding these changes by predicting brain age from MRI scans. Current approaches primarily use T1-weighted magnetic resonance imaging (T1w MRI) data, capturing only structural brain information. To address this limitation, AI-generated Cerebral Blood Volume (AICBV) data, synthesized from non-contrast MRI scans, offers functional insights by revealing subtle blood-tissue contrasts otherwise undetectable in standard imaging. We integrated AICBV with T1w MRI to predict brain age, combining both structural and functional metrics. We developed a deep learning model using a VGG-based architecture for both modalities and combined their predictions using linear regression. Our model achieved a mean absolute error (MAE) of 3.95 years and an $R^2$ of 0.943 on the test set ($n = 288$), outperforming existing models trained on similar data. We have further created gradient-based class activation maps (Grad-CAM) to visualize the regions of the brain that most influenced the model's predictions, providing interpretable insights into the structural and functional contributors to brain aging.