The effect of head motion on brain age prediction using deep convolutional neural networks.

Deep learning can be used effectively to predict participants' age from brain magnetic resonance imaging (MRI) data, and a growing body of evidence suggests that the difference between predicted and chronological age-referred to as brain-predicted age difference (brain-PAD)-is related to various neurological and neuropsychiatric disease states. A crucial aspect of the applicability of brain-PAD as a biomarker of individual brain health is whether and how brain-predicted age is affected by MR image artifacts commonly encountered in clinical settings. To investigate this issue, we trained and validated two different 3D convolutional neural network architectures (CNNs) from scratch and tested the models on a separate dataset consisting of motion-free and motion-corrupted T1-weighted MRI scans from the same participants, the quality of which were rated by neuroradiologists from a clinical diagnostic point of view. Our results revealed a systematic increase in brain-PAD with worsening image quality for both models. This effect was also observed for images that were deemed usable from a clinical perspective, with brains appearing older in medium than in good quality images. These findings were also supported by significant associations found between the brain-PAD and standard image quality metrics indicating larger brain-PAD for lower-quality images. Our results demonstrate a spurious effect of advanced brain aging as a result of head motion and underline the importance of controlling for image quality when using brain-predicted age based on structural neuroimaging data as a proxy measure for brain health.

Predicting mild cognitive impairments from cognitively normal brains using a novel brain age estimation model based on structural magnetic resonance imaging.

Brain age prediction is a practical method used to quantify brain aging and detect neurodegenerative diseases such as Alzheimer's disease (AD). However, very few studies have considered brain age prediction as a biomarker for the conversion of cognitively normal (CN) to mild cognitive impairment (MCI). In this study, we developed a novel brain age prediction model using brain volume and cortical thickness features. We calculated an acceleration of brain age (ABA) derived from the suggested model to estimate different diagnostic groups (CN, MCI, and AD) and to classify CN to MCI and MCI to AD conversion groups. We observed a strong association between ABA and the 3 diagnostic groups. Additionally, the classification models for CN to MCI conversion and MCI to AD conversion exhibited acceptable and robust performances, with area under the curve values of 0.66 and 0.76, respectively. We believe that our proposed model provides a reliable estimate of brain age for elderly individuals and can identify those at risk of progressing from CN to MCI. This model has great potential to reveal a diagnosis associated with a change in cognitive decline.

Brain age predicted using graph convolutional neural network explains neurodevelopmental trajectory in preterm neonates.

OBJECTIVES: Dramatic brain morphological changes occur throughout the third trimester of gestation. In this study, we investigated whether the predicted brain age (PBA) derived from graph convolutional network (GCN) that accounts for cortical morphometrics in third trimester is associated with postnatal abnormalities and neurodevelopmental outcome. METHODS: In total, 577 T1 MRI scans of preterm neonates from two different datasets were analyzed; the NEOCIVET pipeline generated cortical surfaces and morphological features, which were then fed to the GCN to predict brain age. The brain age index (BAI; PBA minus chronological age) was used to determine the relationships among preterm birth (i.e., birthweight and birth age), perinatal brain injuries, postnatal events/clinical conditions, BAI at postnatal scan, and neurodevelopmental scores at 30 months. RESULTS: Brain morphology and GCN-based age prediction of preterm neonates without brain lesions (mean absolute error [MAE]: 0.96 weeks) outperformed conventional machine learning methods using no topological information. Structural equation models (SEM) showed that BAI mediated the influence of preterm birth and postnatal clinical factors, but not perinatal brain injuries, on neurodevelopmental outcome at 30 months of age. CONCLUSIONS: Brain morphology may be clinically meaningful in measuring brain age, as it relates to postnatal factors, and predicting neurodevelopmental outcome. CLINICAL RELEVANCE STATEMENT: Understanding the neurodevelopmental trajectory of preterm neonates through the prediction of brain age using a graph convolutional neural network may allow for earlier detection of potential developmental abnormalities and improved interventions, consequently enhancing the prognosis and quality of life in this vulnerable population. KEY POINTS: •Brain age in preterm neonates predicted using a graph convolutional network with brain morphological changes mediates the pre-scan risk factors and post-scan neurodevelopmental outcomes. •Predicted brain age oriented from conventional deep learning approaches, which indicates the neurodevelopmental status in neonates, shows a lack of sensitivity to perinatal risk factors and predicting neurodevelopmental outcomes. •The new brain age index based on brain morphology and graph convolutional network enhances the accuracy and clinical interpretation of predicted brain age for neonates.

Multidimensional brain-age prediction reveals altered brain developmental trajectory in psychiatric disorders.

Brain-age prediction has emerged as a novel approach for studying brain development. However, brain regions change in different ways and at different rates. Unitary brain-age indices represent developmental status averaged across the whole brain and therefore do not capture the divergent developmental trajectories of various brain structures. This staggered developmental unfolding, determined by genetics and postnatal experience, is implicated in the progression of psychiatric and neurological disorders. We propose a multidimensional brain-age index (MBAI) that provides regional age predictions. Using a database of 556 individuals, we identified clusters of imaging features with distinct developmental trajectories and built machine learning models to obtain brain-age predictions from each of the clusters. Our results show that the MBAI provides a flexible analysis of region-specific brain-age changes that are invisible to unidimensional brain-age. Importantly, brain-ages computed from region-specific feature clusters contain complementary information and demonstrate differential ability to distinguish disorder groups (e.g., depression and oppositional defiant disorder) from healthy controls. In summary, we show that MBAI is sensitive to alterations in brain structures and captures distinct regional change patterns that may serve as biomarkers that contribute to our understanding of healthy and pathological brain development and the characterization and diagnosis of psychiatric disorders.

Comparison of Machine Learning Models for Brain Age Prediction Using Six Imaging Modalities on Middle-Aged and Older Adults.

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.

Mind the gap: Performance metric evaluation in brain-age prediction.

Estimating age based on neuroimaging-derived data has become a popular approach to developing markers for brain integrity and health. While a variety of machine-learning algorithms can provide accurate predictions of age based on brain characteristics, there is significant variation in model accuracy reported across studies. We predicted age in two population-based datasets, and assessed the effects of age range, sample size and age-bias correction on the model performance metrics Pearson's correlation coefficient (r), the coefficient of determination (R2 ), Root Mean Squared Error (RMSE) and Mean Absolute Error (MAE). The results showed that these metrics vary considerably depending on cohort age range; r and R2 values are lower when measured in samples with a narrower age range. RMSE and MAE are also lower in samples with a narrower age range due to smaller errors/brain age delta values when predictions are closer to the mean age of the group. Across subsets with different age ranges, performance metrics improve with increasing sample size. Performance metrics further vary depending on prediction variance as well as mean age difference between training and test sets, and age-bias corrected metrics indicate high accuracy-also for models showing poor initial performance. In conclusion, performance metrics used for evaluating age prediction models depend on cohort and study-specific data characteristics, and cannot be directly compared across different studies. Since age-bias corrected metrics generally indicate high accuracy, even for poorly performing models, inspection of uncorrected model results provides important information about underlying model attributes such as prediction variance.

Brain Age Prediction: A Comparison between Machine Learning Models Using Brain Morphometric Data.

Brain structural morphology varies over the aging trajectory, and the prediction of a person's age using brain morphological features can help the detection of an abnormal aging process. Neuroimaging-based brain age is widely used to quantify an individual's brain health as deviation from a normative brain aging trajectory. Machine learning approaches are expanding the potential for accurate brain age prediction but are challenging due to the great variety of machine learning algorithms. Here, we aimed to compare the performance of the machine learning models used to estimate brain age using brain morphological measures derived from structural magnetic resonance imaging scans. We evaluated 27 machine learning models, applied to three independent datasets from the Human Connectome Project (HCP, n = 1113, age range 22-37), the Cambridge Centre for Ageing and Neuroscience (Cam-CAN, n = 601, age range 18-88), and the Information eXtraction from Images (IXI, n = 567, age range 19-86). Performance was assessed within each sample using cross-validation and an unseen test set. The models achieved mean absolute errors of 2.75-3.12, 7.08-10.50, and 8.04-9.86 years, as well as Pearson's correlation coefficients of 0.11-0.42, 0.64-0.85, and 0.63-0.79 between predicted brain age and chronological age for the HCP, Cam-CAN, and IXI samples, respectively. We found a substantial difference in performance between models trained on the same data type, indicating that the choice of model yields considerable variation in brain-predicted age. Furthermore, in three datasets, regularized linear regression algorithms achieved similar performance to nonlinear and ensemble algorithms. Our results suggest that regularized linear algorithms are as effective as nonlinear and ensemble algorithms for brain age prediction, while significantly reducing computational costs. Our findings can serve as a starting point and quantitative reference for future efforts at improving brain age prediction using machine learning models applied to brain morphometric data.

Predicting brain age during typical and atypical development based on structural and functional neuroimaging.

Exploring typical and atypical brain developmental trajectories is very important for understanding the normal pace of brain development and the mechanisms by which mental disorders deviate from normal development. A precise and sex-specific brain age prediction model is desirable for investigating the systematic deviation and individual heterogeneity of disorders associated with atypical brain development, such as autism spectrum disorders. In this study, we used partial least squares regression and the stacking algorithm to establish a sex-specific brain age prediction model based on T1-weighted structural magnetic resonance imaging and resting-state functional magnetic resonance imaging. The model showed good generalization and high robustness on four independent datasets with different ethnic information and age ranges. A predictor weights analysis showed the differences and similarities in changes in structure and function during brain development. At the group level, the brain age gap estimation for autistic patients was significantly smaller than that for healthy controls in both the ABIDE dataset and the healthy brain network dataset, which suggested that autistic patients as a whole exhibited the characteristics of delayed development. However, within the ABIDE dataset, the premature development group had significantly higher Autism Diagnostic Observation Schedule (ADOS) scores than those of the delayed development group, implying that individuals with premature development had greater severity. Using these findings, we built an accurate typical brain development trajectory and developed a method of atypical trajectory analysis that considers sex differences and individual heterogeneity. This strategy may provide valuable clues for understanding the relationship between brain development and mental disorders.

Multimodal brain-age prediction and cardiovascular risk: The Whitehall II MRI sub-study.

Brain age is becoming a widely applied imaging-based biomarker of neural aging and potential proxy for brain integrity and health. We estimated multimodal and modality-specific brain age in the Whitehall II (WHII) MRI cohort using machine learning and imaging-derived measures of gray matter (GM) morphology, white matter microstructure (WM), and resting state functional connectivity (FC). The results showed that the prediction accuracy improved when multiple imaging modalities were included in the model (R2 = 0.30, 95% CI [0.24, 0.36]). The modality-specific GM and WM models showed similar performance (R2 = 0.22 [0.16, 0.27] and R2 = 0.24 [0.18, 0.30], respectively), while the FC model showed the lowest prediction accuracy (R2 = 0.002 [-0.005, 0.008]), indicating that the FC features were less related to chronological age compared to structural measures. Follow-up analyses showed that FC predictions were similarly low in a matched sub-sample from UK Biobank, and although FC predictions were consistently lower than GM predictions, the accuracy improved with increasing sample size and age range. Cardiovascular risk factors, including high blood pressure, alcohol intake, and stroke risk score, were each associated with brain aging in the WHII cohort. Blood pressure showed a stronger association with white matter compared to gray matter, while no differences in the associations of alcohol intake and stroke risk with these modalities were observed. In conclusion, machine-learning based brain age prediction can reduce the dimensionality of neuroimaging data to provide meaningful biomarkers of individual brain aging. However, model performance depends on study-specific characteristics including sample size and age range, which may cause discrepancies in findings across studies.

Brain status modeling with non-negative projective dictionary learning.

Accurate prediction of individuals' brain age is critical to establish a baseline for normal brain development. This study proposes to model brain development with a novel non-negative projective dictionary learning (NPDL) approach, which learns a discriminative representation of multi-modal neuroimaging data for predicting brain age. Our approach encodes the variability of subjects in different age groups using separate dictionaries, projecting features into a low-dimensional manifold such that information is preserved only for the corresponding age group. The proposed framework improves upon previous discriminative dictionary learning methods by incorporating orthogonality and non-negativity constraints, which remove representation redundancy and perform implicit feature selection. We study brain development on multi-modal brain imaging data from the PING dataset (N = 841, age = 3-21 years). The proposed analysis uses our NDPL framework to predict the age of subjects based on cortical measures from T1-weighted MRI and connectome from diffusion weighted imaging (DWI). We also investigate the association between age prediction and cognition, and study the influence of gender on prediction accuracy. Experimental results demonstrate the usefulness of NDPL for modeling brain development.

The maternal brain: Region-specific patterns of brain aging are traceable decades after childbirth.

Pregnancy involves maternal brain adaptations, but little is known about how parity influences women's brain aging trajectories later in life. In this study, we replicated previous findings showing less apparent brain aging in women with a history of childbirths, and identified regional brain aging patterns linked to parity in 19,787 middle- and older-aged women. Using novel applications of brain-age prediction methods, we found that a higher number of previous childbirths were linked to less apparent brain aging in striatal and limbic regions. The strongest effect was found in the accumbens-a key region in the mesolimbic reward system, which plays an important role in maternal behavior. While only prospective longitudinal studies would be conclusive, our findings indicate that subcortical brain modulations during pregnancy and postpartum may be traceable decades after childbirth.

Improved prediction of brain age using multimodal neuroimaging data.

Brain age prediction based on imaging data and machine learning (ML) methods has great potential to provide insights into the development of cognition and mental disorders. Though different ML models have been proposed, a systematic comparison of ML models in combination with imaging features derived from different modalities is still needed. In this study, we evaluate the prediction performance of 36 combinations of imaging features and ML models including deep learning. We utilize single and multimodal brain imaging data including MRI, DTI, and rs-fMRI from a large data set with 839 subjects. Our study is a follow-up to the initial work (Liang et al., 2019. Human Brain Mapping) to investigate different analytic strategies to combine data from MRI, DTI, and rs-fMRI with the goal to improve brain age prediction accuracy. Additionally, the traditional approach to predicting the brain age gap has been shown to have a systematic bias. The potential nonlinear relationship between the brain age gap and chronological age has not been thoroughly tested. Here we propose a new method to correct the systematic bias of brain age gap by taking gender, chronological age, and their interactions into consideration. As the true brain age is unknown and may deviate from chronological age, we further examine whether various levels of behavioral performance across subjects predict their brain age estimated from neuroimaging data. This is an important step to quantify the practical implication of brain age prediction. Our findings are helpful to advance the practice of optimizing different analytic methodologies in brain age prediction.

Brain age prediction: Cortical and subcortical shape covariation in the developing human brain.

Cortical development is characterized by distinct spatial and temporal patterns of maturational changes across various cortical shape measures. There is a growing interest in summarizing complex developmental patterns into a single index, which can be used to characterize an individual's brain age. We conducted this study with two primary aims. First, we sought to quantify covariation patterns for a variety of cortical shape measures, including cortical thickness, gray matter volume, surface area, mean curvature, and travel depth, as well as white matter volume, and subcortical gray matter volume. We examined these measures in a sample of 869 participants aged 5-18 from the Healthy Brain Network (HBN) neurodevelopmental cohort using the Joint and Individual Variation Explained (Lock et al., 2013) method. We validated our results in an independent dataset from the Nathan Kline Institute - Rockland Sample (NKI-RS; N = 210) and found remarkable consistency for some covariation patterns. Second, we assessed whether covariation patterns in the brain can be used to accurately predict a person's chronological age. Using ridge regression, we showed that covariation patterns can predict chronological age with high accuracy, reflected by our ability to cross-validate our model in an independent sample with a correlation coefficient of 0.84 between chronologic and predicted age. These covariation patterns also predicted sex with high accuracy (AUC = 0.85), and explained a substantial portion of variation in full scale intelligence quotient (R2 = 0.10). In summary, we found significant covariation across different cortical shape measures and subcortical gray matter volumes. In addition, each shape measure exhibited distinct covariations that could not be accounted for by other shape measures. These covariation patterns accurately predicted chronological age, sex and general cognitive ability. In a subset of NKI-RS, test-retest (<1 month apart, N = 120) and longitudinal scans (1.22 ±â€¯0.29 years apart, N = 77) were available, allowing us to demonstrate high reliability for the prediction models obtained and the ability to detect subtle differences in the longitudinal scan interval among participants (median and median absolute deviation of absolute differences between predicted age difference and real age difference = 0.53 ±â€¯0.47 years, r = 0.24, p-value = 0.04).

Investigating systematic bias in brain age estimation with application to post-traumatic stress disorders.

Brain age prediction using machine-learning techniques has recently attracted growing attention, as it has the potential to serve as a biomarker for characterizing the typical brain development and neuropsychiatric disorders. Yet one long-standing problem is that the predicted brain age is overestimated in younger subjects and underestimated in older. There is a plethora of claims as to the bias origins, both methodologically and in data itself. With a large neuroanatomical dataset (N = 2,026; 6-89 years of age) from multiple shared datasets, we show this bias is neither data-dependent nor specific to particular method including deep neural network. We present an alternative account that offers a statistical explanation for the bias and describe a simple, yet efficient, method using general linear model to adjust the bias. We demonstrate the effectiveness of bias adjustment with a large multi-modal neuroimaging data (N = 804; 8-21 years of age) for both healthy controls and post-traumatic stress disorders patients obtained from the Philadelphia Neurodevelopmental Cohort.

An unbiased data-driven age-related structural brain parcellation for the identification of intrinsic brain volume changes over the adult lifespan.

This study aims to elucidate age-related intrinsic brain volume changes over the adult lifespan using an unbiased data-driven structural brain parcellation. Anatomical brain images from a cohort of 293 healthy volunteers ranging in age from 21 to 86 years were analyzed using independent component analysis (ICA). ICA-based parcellation identified 192 component images, of which 174 (90.6%) showed a significant negative correlation with age and with some components being more vulnerable to aging effects than others. Seven components demonstrated a convex slope with aging; 3 components had an inverted U-shaped trajectory, and 4 had a U-shaped trajectory. Linear combination of 86 components provided reliable prediction of chronological age with a mean absolute prediction error of approximately 7.2 years. Structural co-variation analysis showed strong interhemispheric, short-distance positive correlations and long-distance, inter-lobar negative correlations. Estimated network measures either exhibited a U- or an inverted U-shaped relationship with age, with the vertex occurring at approximately 45-50 years. Overall, these findings could contribute to our knowledge about healthy brain aging and could help provide a framework to distinguish the normal aging processes from that associated with age-related neurodegenerative diseases.

A ResNet mini architecture for brain age prediction.

The brain presents age-related structural and functional changes in the human life, with different extends between subjects and groups. Brain age prediction can be used to evaluate the development and aging of human brain, as well as providing valuable information for neurodevelopment and disease diagnosis. Many contributions have been made for this purpose, resorting to different machine learning methods. To solve this task and reduce memory resource consumption, we develop a mini architecture of only 10 layers by modifying the deep residual neural network (ResNet), named ResNet mini architecture. To support the ResNet mini architecture in brain age prediction, the brain age dataset (OpenNeuro #ds000228) that consists of 155 study participants (three classes) and the Alzheimer MRI preprocessed dataset that consists of 6400 images (four classes) are employed. We compared the performance of the ResNet mini architecture with other popular networks using the two considered datasets. Experimental results show that the proposed architecture exhibits generality and robustness with high accuracy and less parameter number.

Brain Age Prediction Using Multi-Hop Graph Attention Combined with Convolutional Neural Network.

Convolutional neural networks (CNNs) have been used widely to predict biological brain age based on brain magnetic resonance (MR) images. However, CNNs focus mainly on spatially local features and their aggregates and barely on the connective information between distant regions. To overcome this issue, we propose a novel multi-hop graph attention (MGA) module that exploits both the local and global connections of image features when combined with CNNs. After insertion between convolutional layers, MGA first converts the convolution-derived feature map into graph-structured data by using patch embedding and embedding-distance-based scoring. Multi-hop connections between the graph nodes are modeled by using the Markov chain process. After performing multi-hop graph attention, MGA re-converts the graph into an updated feature map and transfers it to the next convolutional layer. We combined the MGA module with sSE (spatial squeeze and excitation)-ResNet18 for our final prediction model (MGA-sSE-ResNet18) and performed various hyperparameter evaluations to identify the optimal parameter combinations. With 2788 three-dimensional T1-weighted MR images of healthy subjects, we verified the effectiveness of MGA-sSE-ResNet18 with comparisons to four established, general-purpose CNNs and two representative brain age prediction models. The proposed model yielded an optimal performance with a mean absolute error of 2.822 years and Pearson's correlation coefficient (PCC) of 0.968, demonstrating the potential of the MGA module to improve the accuracy of brain age prediction.

Predicting Brain Age and Gender from Brain Volume Data Using Variational Quantum Circuits.

The morphology of the brain undergoes changes throughout the aging process, and accurately predicting a person's brain age and gender using brain morphology features can aid in detecting atypical brain patterns. Neuroimaging-based estimation of brain age is commonly used to assess an individual's brain health relative to a typical aging trajectory, while accurately classifying gender from neuroimaging data offers valuable insights into the inherent neurological differences between males and females. In this study, we aimed to compare the efficacy of classical machine learning models with that of a quantum machine learning method called a variational quantum circuit in estimating brain age and predicting gender based on structural magnetic resonance imaging data. We evaluated six classical machine learning models alongside a quantum machine learning model using both combined and sub-datasets, which included data from both in-house collections and public sources. The total number of participants was 1157, ranging from ages 14 to 89, with a gender distribution of 607 males and 550 females. Performance evaluation was conducted within each dataset using training and testing sets. The variational quantum circuit model generally demonstrated superior performance in estimating brain age and gender classification compared to classical machine learning algorithms when using the combined dataset. Additionally, in benchmark sub-datasets, our approach exhibited better performance compared to previous studies that utilized the same dataset for brain age prediction. Thus, our results suggest that variational quantum algorithms demonstrate comparable effectiveness to classical machine learning algorithms for both brain age and gender prediction, potentially offering reduced error and improved accuracy.

Inter-site generalizability of EEG based age prediction algorithms in the preterm infant.

Objective. To overcome the effects of site differences in EEG-based brain age prediction in preterm infants.Approach. We used a 'bag of features' with a combination function estimated using support vector regression (SVR) and feature selection (filter then wrapper) to predict post-menstrual age (PMA). The SVR was trained on a dataset containing 138 EEG recordings from 37 preterm infants (site 1). A separate set of 36 EEG recordings from 36 preterm infants was used to validate the age predictor (site 2). The feature distributions were compared between sites and a restricted feature set was constructed using only features that were not significantly different between sites. The mean absolute error between predicted age and PMA was used to define the accuracy of prediction and successful validation was defined as no significant differences in error between site 1 (cross-validation) and site 2.Main results. The age predictor based on all features and trained on site 1 was not validated on site 2 (p< 0.001; MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 2.1 weeks,n= 36). The MAE was improved by training on a restricted features set (MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 1.1 weeks,n= 36), resulting in a validated age predictor when applied to site 2 (p= 0.68). The features selected from the restricted feature set when training on site 1 closely aligned with features selected when trained on a combination of data from site 1 and site 2.Significance. The ability of EEG classifiers, such as brain age prediction, to maintain accuracy on data collected at other sites may be challenged by unexpected, site-dependent differences in EEG signals. Permitting a small amount of data leakage between sites improves generalization, leading towards universal methods of EEG interpretation in preterm infants.

Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex.

Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-ß, more advanced stages (AT) of AD pathology and APOE-ε4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury.