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The intricate dynamics of brain aging, especially the neurodegenerative mechanisms driving accelerated (ABA) and resilient brain aging (RBA), are pivotal in neuroscience. Understanding the temporal dynamics of these phenotypes is crucial for identifying vulnerabilities to cognitive decline and neurodegenerative diseases. Currently, there is a lack of comprehensive understanding of the temporal dynamics and neuroimaging biomarkers linked to ABA and RBA. This study addressed this gap by utilizing a large-scale UK Biobank (UKB) cohort, with the aim to elucidate brain aging heterogeneity and establish the foundation for targeted interventions. Employing Lasso regression on multimodal neuroimaging data, structural MRI (sMRI), diffusion MRI (dMRI), and resting-state functional MRI (rsfMRI), we predicted the brain age and classified individuals into ABA and RBA cohorts. Our findings identified 1949 subjects (6.2%) as representative of the ABA subpopulation and 3203 subjects (10.1%) as representative of the RBA subpopulation. Additionally, the Discriminative Event-Based Model (DEBM) was applied to estimate the sequence of biomarker changes across aging trajectories. Our analysis unveiled distinct central ordering patterns between the ABA and RBA cohorts, with profound implications for understanding cognitive decline and vulnerability to neurodegenerative disorders. Specifically, the ABA cohort exhibited early degeneration in four functional networks and two cognitive domains, with cortical thinning initially observed in the right hemisphere, followed by the temporal lobe. In contrast, the RBA cohort demonstrated initial degeneration in the three functional networks, with cortical thinning predominantly in the left hemisphere and white matter microstructural degeneration occurring at more advanced stages. The detailed aging progression timeline constructed through our DEBM analysis positioned subjects according to their estimated stage of aging, offering a nuanced view of the aging brain's alterations. This study holds promise for the development of targeted interventions aimed at mitigating age-related cognitive decline. [ABSTRACT FROM AUTHOR]

Accelerated brain aging (ABA) intricately links with age-associated neurodegenerative and neuropsychiatric diseases, emphasizing the critical need for a nuanced exploration of heterogeneous ABA patterns. This investigation leveraged data from the UK Biobank (UKB) for a comprehensive analysis, utilizing structural magnetic resonance imaging (sMRI), diffusion magnetic resonance imaging (dMRI), and resting-state functional magnetic resonance imaging (rsfMRI) from 31,621 participants. Pre-processing employed tools from the FMRIB Software Library (FSL, version 5.0.10), FreeSurfer, DTIFIT, and MELODIC, seamlessly integrated into the UKB imaging processing pipeline. The Lasso algorithm was employed for brain-age prediction, utilizing derived phenotypes obtained from brain imaging data. Subpopulations of accelerated brain aging (ABA) and resilient brain aging (RBA) were delineated based on the error between actual age and predicted brain age. The ABA subgroup comprised 1949 subjects (experimental group), while the RBA subgroup comprised 3203 subjects (control group). Semi-supervised heterogeneity through discriminant analysis (HYDRA) refined and characterized the ABA subgroups based on distinctive neuroimaging features. HYDRA systematically stratified ABA subjects into three subtypes: SubGroup 2 exhibited extensive gray-matter atrophy, distinctive white-matter patterns, and unique connectivity features, displaying lower cognitive performance; SubGroup 3 demonstrated minimal atrophy, superior cognitive performance, and higher physical activity; and SubGroup 1 occupied an intermediate position. This investigation underscores pronounced structural and functional heterogeneity in ABA, revealing three subtypes and paving the way for personalized neuroprotective treatments for age-related neurological, neuropsychiatric, and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In the realm of cognitive science, the phenomenon of "successful cognitive aging" stands as a hallmark of individuals who exhibit cognitive abilities surpassing those of their age-matched counterparts. However, it is paramount to underscore a significant gap in the current research, which is marked by a paucity of comprehensive inquiries that deploy substantial sample sizes to methodically investigate the cerebral biomarkers and contributory elements underpinning this cognitive success. It is within this context that our present study emerges, harnessing data derived from the UK Biobank. In this study, a highly selective cohort of 1060 individuals aged 65 and above was meticulously curated from a larger pool of 17,072 subjects. The selection process was guided by their striking cognitive resilience, ascertained via rigorous evaluation encompassing both generic and specific cognitive assessments, compared to their peers within the same age stratum. Notably, the cognitive abilities of the chosen participants closely aligned with the cognitive acumen commonly observed in middle-aged individuals. Our study leveraged a comprehensive array of neuroimaging-derived metrics, obtained from three Tesla MRI scans (T1-weighted images, dMRI, and resting-state fMRI). The metrics included image-derived phenotypes (IDPs) that addressed grey matter morphology, the strength of brain network connectivity, and the microstructural attributes of white matter. Statistical analyses were performed employing ANOVA, Mann–Whitney U tests, and chi-square tests to evaluate the distinctive aspects of IDPs pertinent to the domain of successful cognitive aging. Furthermore, these analyses aimed to elucidate lifestyle practices that potentially underpin the maintenance of cognitive acumen throughout the aging process. Our findings unveiled a robust and compelling association between heightened cognitive aptitude and the integrity of white matter structures within the brain. Furthermore, individuals who exhibited successful cognitive aging demonstrated markedly enhanced activity in the cerebral regions responsible for auditory perception, voluntary motor control, memory retention, and emotional regulation. These advantageous cognitive attributes were mirrored in the health-related lifestyle choices of the surveyed cohort, characterized by elevated educational attainment, a lower incidence of smoking, and a penchant for moderate alcohol consumption. Moreover, they displayed superior grip strength and enhanced walking speeds. Collectively, these findings furnish valuable insights into the multifaceted determinants of successful cognitive aging, encompassing both neurobiological constituents and lifestyle practices. Such comprehensive comprehension significantly contributes to the broader discourse on aging, thereby establishing a solid foundation for the formulation of targeted interventions aimed at fostering cognitive well-being among aging populations. [ABSTRACT FROM AUTHOR]

Machine learning (ML) has transformed neuroimaging research by enabling accurate predictions and feature extraction from large datasets. In this study, we investigate the application of six ML algorithms (Lasso, relevance vector regression, support vector regression, extreme gradient boosting, category boost, and multilayer perceptron) to predict brain age for middle-aged and older adults, which is a crucial area of research in neuroimaging. Despite the plethora of proposed ML models, there is no clear consensus on how to achieve better performance in brain age prediction for this population. Our study stands out by evaluating the impact of both ML algorithms and image modalities on brain age prediction performance using a large cohort of cognitively normal adults aged 44.6 to 82.3 years old (N = 27,842) with six image modalities. We found that the predictive performance of brain age is more reliant on the image modalities used than the ML algorithms employed. Specifically, our study highlights the superior performance of T1-weighted MRI and diffusion-weighted imaging and demonstrates that multi-modality-based brain age prediction significantly enhances performance compared to unimodality. Moreover, we identified Lasso as the most accurate ML algorithm for predicting brain age, achieving the lowest mean absolute error in both single-modality and multi-modality predictions. Additionally, Lasso also ranked highest in a comprehensive evaluation of the relationship between BrainAGE and the five frequently mentioned BrainAGE-related factors. Notably, our study also shows that ensemble learning outperforms Lasso when computational efficiency is not a concern. Overall, our study provides valuable insights into the development of accurate and reliable brain age prediction models for middle-aged and older adults, with significant implications for clinical practice and neuroimaging research. Our findings highlight the importance of image modality selection and emphasize Lasso as a promising ML algorithm for brain age prediction. [ABSTRACT FROM AUTHOR]

The cognitive reserve (CR) hypothesis is reinforced by negative moderating effects, suggesting that those with higher CR are less reliant on brain structure for cognitive function. Previous research on CR's moderating effects yielded inconsistent results, motivating our 3 studies using UK Biobank data. Study I examined five CR proxies' moderating effects on global, lobar, and regional brain-cognition models; study II extended study I by using a larger sample size; and study III investigated age-related moderating effects on the hippocampal regions. In study I, most moderating effects were negative and none survived the multiple comparison correction, but study II identified 13 global-level models with significant negative moderating effects that survived correction. Study III showed age influenced CR proxies' moderating effects in hippocampal regions. Our findings suggest that the effects of CR proxies on brain integrity and cognition varied depending on the proxy used, brain integrity indicators, cognitive domain, and age group. This study offers significant insights regarding the importance of CR for brain integrity and cognitive outcomes. [ABSTRACT FROM AUTHOR]