Popescu, S. G. | bioRxiv Science

bioRxiv2022

Sex differences in predictors and regional patterns of brain-age-gap estimates

BackgroundThe brain-age-gap estimate (brainAGE) quantifies the difference between chronological age and age predicted by applying machine-learning models to neuroimaging data, and is considered a biomarker of brain health. Understanding sex-differences in brainAGE is a significant step toward precision medicine. MethodsGlobal and local brainAGE (G-brainAGE and L-brainAGE, respectively) were computed by applying machine learning algorithms to brain structural magnetic resonance imaging data from 1113 healthy young adults (54.45% females; age range: 22-37 years) participating in the Human Connectome Project. Sex-differences were determined in G-brainAGE and L-brainAGE. Random forest regression was used to determine sex-specific associations between G-brainAGE and non-imaging measures pertaining to sociodemographic characteristics and mental, physical, and cognitive functions. ResultsL-brainAGE showed sex-specific differences in brain ageing. In females, compared to males, L-brainAGE was higher in the cerebellum and brainstem and lower in the prefrontal cortex and insula. Although sex-differences in G-brainAGE were minimal, associations between G-brainAGE and non-imaging measures differed between sexes with the exception for poor sleep quality, which was common to both. The most important predictor of higher G-brainAGE was non-white race in males and systolic blood pressure in females. ConclusionsThe results demonstrate the value of applying sex-specific analyses and machine learning methods to advance our understanding of sex-related differences in factors that influence the rate of brain ageing and provide a foundation for targeted interventions.

neuroscience↗

bioRxiv2021

A U-Net model of local brain-age

AO_SCPLOWBSTRACTC_SCPLOWWe propose a new framework for estimating neuroimaging-derived "brain-age" at a local level within the brain, using deep learning. The local approach, contrary to existing global methods, provides spatial information on anatomical patterns of brain ageing. We trained a U-Net model using brain MRI scans from n=3463 healthy people (aged 18-90 years) to produce individualised 3D maps of brain-predicted age. When testing on n=692 healthy people, we found a median (across participant) mean absolute error (within participant) of 9.5 years. Performance was more accurate (MAE around 7 years) in the prefrontal cortex and periventricular areas. We also introduce a new voxelwise method to reduce the age-bias when predicting local brain-age "gaps". To validate local brain-age predictions, we tested the model in people with mild cognitive impairment or dementia using data from OASIS3 (n=267). Different local brain-age patterns were evident between healthy controls and people with mild cognitive impairment or dementia, particularly in subcortical regions such as the accumbens, putamen, pallidum, hippocampus and amygdala. Comparing groups based on mean local brain-age over regions-of-interest resulted in large effects sizes, with Cohens d values >1.5, for example when comparing people with stable and progressive mild cognitive impairment. Our local brain-age framework has the potential to provide spatial information leading to a more mechanistic understanding of individual differences in patterns of brain ageing in health and disease.

neuroscience↗