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Brain age can be estimated using different Magnetic Resonance Imaging (MRI) modalities including diffusion MRI. Recent studies demonstrated that white matter (WM) tracts that share the same function might experience similar alterations. Therefore, in this work, we sought to investigate such issue focusing on five WM bundles holding that feature that is Association, Brainstem, Commissural, Limbic and Projection fibers, respectively. For each tract group, we estimated brain age for 15,335 healthy participants from United Kingdom Biobank relying on diffusion MRI data derived endophenotypes, Bayesian ridge regression modeling and 10 fold-cross validation. Furthermore, we estimated brain age for an Ensemble model that gathers all the considered WM bundles. Association analysis was subsequently performed between the estimated brain age delta as resulting from the six models, that is for each tract group as well as for the Ensemble model, and 38 daily life style measures, 14 cardiac risk factors and cardiovascular magnetic resonance imaging features and genetic variants. The Ensemble model that used all tracts from all fiber groups (FG) performed better than other models to estimate brain age. Limbic tracts based model reached the highest accuracy with a Mean Absolute Error (MAE) of 5.08, followed by the Commissural ([Formula: see text]), Association ([Formula: see text]), and Projection ([Formula: see text]) ones. The Brainstem tracts based model was the less accurate achieving a MAE of 5.86. Accordingly, our study suggests that the Limbic tracts experience less brain aging or allows for more accurate estimates compared to other tract groups. Moreover, the results suggest that Limbic tract leads to the largest number of significant associations with daily lifestyle factors than the other tract groups. Lastly, two SNPs were significantly (p value [Formula: see text]) associated with brain age delta in the Projection fibers. Those SNPs are mapped to HIST1H1A and SLC17A3 genes., (© 2021. The Author(s).)

Diffusion weighted imaging (DWI) is a widely recognized neuroimaging technique to evaluate the microstructure of brain white matter. The objective of this study is to establish an improved automated DWI marker for estimating white matter integrity and investigating ageing related cognitive decline. The concept of Wasserstein distance was introduced to help establish a new measure: difference in distribution functions (DDF), which captures the difference of reshaping one's mean diffusivity (MD) distribution to a reference MD distribution. This new DWI measure was developed using a population-based cohort (n=19,369) from the UK Biobank. Validation was conducted using the data drawn from two independent cohorts: the Sydney Memory and Ageing Study, a community-dwelling sample (n=402), and the Renji Cerebral Small Vessel Disease Cohort Study (RCCS), which consisted of cerebral small vessel disease (CSVD) patients (n=171) and cognitively normal controls (NC) (n=43). DDF was associated with age across all three samples and better explained the variance of changes than other established DWI measures, such as fractional anisotropy, mean diffusivity and peak width of skeletonized mean diffusivity (PSMD). Significant correlations between DDF and cognition were found in the UK Biobank cohort and the MAS cohort. Binary logistic analysis and receiver operator characteristic curve analysis of RCCS demonstrated that DDF had higher sensitivity in distinguishing CSVD patients from NC than the other DWI measures. To demonstrate the flexibility of DDF, we calculated regional DDF which also showed significant correlation with age and cognition. DDF can be used as a marker for monitoring the white matter microstructural changes and ageing related cognitive decline in the elderly., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

The human default mode network (DMN) is implicated in several unique mental capacities. In this study, we tested whether brain-wide interregional communication in the DMN can be derived from population variability in intrinsic activity fluctuations, gray-matter morphology, and fiber tract anatomy. In a sample of 10,000 UK Biobank participants, pattern-learning algorithms revealed functional coupling states in the DMN that are linked to connectivity profiles between other macroscopical brain networks. In addition, DMN gray matter volume was covaried with white matter microstructure of the fornix. Collectively, functional and structural patterns unmasked a possible division of labor within major DMN nodes: Subregions most critical for cortical network interplay were adjacent to subregions most predictive of fornix fibers from the hippocampus that processes memories and places., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)