Significant Acceleration of Regional Brain Aging and Atrophy After Mild Traumatic Brain Injury.

Brain regions' rates of age-related volumetric change after traumatic brain injury (TBI) are unknown. Here, we quantify these rates cross-sectionally in 113 persons with recent mild TBI (mTBI), whom we compare against 3 418 healthy controls (HCs). Regional gray matter (GM) volumes were extracted from magnetic resonance images. Linear regression yielded regional brain ages and the annualized average rates of regional GM volume loss. These results were compared across groups after accounting for sex and intracranial volume. In HCs, the steepest rates of volume loss were recorded in the nucleus accumbens, amygdala, and lateral orbital sulcus. In mTBI, approximately 80% of GM structures had significantly steeper rates of annual volume loss than in HCs. The largest group differences involved the short gyri of the insula and both the long gyrus and central sulcus of the insula. No significant sex differences were found in the mTBI group, regional brain ages being the oldest in prefrontal and temporal structures. Thus, mTBI involves significantly steeper regional GM loss rates than in HCs, reflecting older-than-expected regional brain ages.

Anatomically interpretable deep learning of brain age captures domain-specific cognitive impairment.

The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate from their typical trajectories. MRI-derived brain age (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or that lack neuroanatomic interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training on the MRIs of 4,681 cognitively normal (CN) participants and testing on 1,170 CN participants from an independent sample. BA estimation errors are notably lower than those of previous studies. At both individual and cohort levels, the CNN provides detailed anatomic maps of brain aging patterns that reveal sex dimorphisms and neurocognitive trajectories in adults with mild cognitive impairment (MCI, N = 351) and Alzheimer's disease (AD, N = 359). In individuals with MCI (54% of whom were diagnosed with dementia within 10.9 y from MRI acquisition), BA is significantly better than CA in capturing dementia symptom severity, functional disability, and executive function. Profiles of sex dimorphism and lateralization in brain aging also map onto patterns of neuroanatomic change that reflect cognitive decline. Significant associations between BA and neurocognitive measures suggest that the proposed framework can map, systematically, the relationship between aging-related neuroanatomy changes in CN individuals and in participants with MCI or AD. Early identification of such neuroanatomy changes can help to screen individuals according to their AD risk.

Regional Neuroanatomic Effects on Brain Age Inferred Using Magnetic Resonance Imaging and Ridge Regression.

The biological age of the brain differs from its chronological age (CA) and can be used as biomarker of neural/cognitive disease processes and as predictor of mortality. Brain age (BA) is often estimated from magnetic resonance images (MRIs) using machine learning (ML) that rarely indicates how regional brain features contribute to BA. Leveraging an aggregate training sample of 3 418 healthy controls (HCs), we describe a ridge regression model that quantifies each region's contribution to BA. After model testing on an independent sample of 651 HCs, we compute the coefficient of partial determination R¯p2 for each regional brain volume to quantify its contribution to BA. Model performance is also evaluated using the correlation r between chronological and biological ages, the mean absolute error (MAE ) and mean squared error (MSE) of BA estimates. On training data, r=0.92, MSE=70.94 years, MAE=6.57 years, and R¯2=0.81; on test data, r=0.90, MSE=81.96 years, MAE=7.00 years, and R¯2=0.79. The regions whose volumes contribute most to BA are the nucleus accumbens (R¯p2=7.27%), inferior temporal gyrus (R¯p2=4.03%), thalamus (R¯p2=3.61%), brainstem (R¯p2=3.29%), posterior lateral sulcus (R¯p2=3.22%), caudate nucleus (R¯p2=3.05%), orbital gyrus (R¯p2=2.96%), and precentral gyrus (R¯p2=2.80%). Our ridge regression, although outperformed by the most sophisticated ML approaches, identifies the importance and relative contribution of each brain structure to overall BA. Aside from its interpretability and quasi-mechanistic insights, our model can be used to validate future ML approaches for BA estimation.