Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults.

Characterizing age- and risk-related hippocampal vulnerabilities may inform about the neural underpinnings of cognitive decline. We studied the impact of three risk-factors, Apolipoprotein (APOE)-ε4, a family history of dementia, and central obesity, on the CA1, CA2/3, dentate gyrus and subiculum of 158 cognitively healthy adults (38-71 years). Subfields were labelled with the Automatic Segmentation of Hippocampal Subfields and FreeSurfer (version 6) protocols. Volumetric and microstructural measurements from quantitative magnetization transfer and Neurite Orientation Density and Dispersion Imaging were extracted for each subfield and reduced to three principal components capturing apparent myelin/neurite packing, size/complexity, and metabolism. Aging was associated with an inverse U-shaped curve on myelin/neurite packing and affected all subfields. Obesity led to reductions in myelin/neurite packing and size/complexity regardless of APOE and family history of dementia status. However, amongst individuals with a healthy Waist-Hip-Ratio, APOE ε4 carriers showed lower size/complexity than non-carriers. Segmentation protocol type did not affect this risk pattern. These findings reveal interactive effects between APOE and central obesity on the hippocampal formation of cognitively healthy adults.

Precommissural and postcommissural fornix microstructure in healthy aging and cognition.

The fornix is a key tract of the hippocampal formation, whose status is presumed to contribute to age-related cognitive decline. The precommissural and postcommissural fornix subdivisions form respective basal forebrain/frontal and diencephalic networks that may differentially affect aging and cognition. We employed multi-parametric magnetic resonance imaging (MRI) including neurite orientation density and dispersion imaging, quantitative magnetization transfer (qMT), and T1-relaxometry MRI to investigate the microstructural properties of these fornix subdivisions and their relationship with aging and cognition in 149 asymptomatic participants (38-71 years). Aging was associated with increased free water signal and reductions in myelin-sensitive R1 and qMT indices but no apparent axon density differences in both precommissural and postcommissural fibers. Precommissural relative to postcommissural fibers showed a distinct microstructural pattern characterised by larger free water signal and axon orientation dispersion, with lower apparent myelin and axon density. Furthermore, differences in postcommissural microstructure were related to performance differences in object-location paired-associate learning. These results provide novel in vivo neuroimaging evidence for distinct microstructural properties of precommissural and postcommissural fibers that are consistent with their anatomy as found in axonal tracer studies, as well as for a contribution of postcommissural fibers to the learning of spatial configurations.

Structural connections support emotional connections: Uncinate Fasciculus microstructure is related to the ability to decode facial emotion expressions.

The Uncinate Fasciculus (UF) is an association fibre tract connecting regions in the frontal and anterior temporal lobes. UF disruption is seen in several disorders associated with impaired social behaviour, but its functional role is unclear. Here we set out to test the hypothesis that the UF is important for facial expression processing, an ability fundamental to adaptive social behaviour. In two separate experiments in healthy adults, we used high-angular resolution diffusion-weighted imaging (HARDI) and constrained spherical deconvolution (CSD) tractography to virtually dissect the UF, plus a control tract (the corticospinal tract (CST)), and quantify, via fractional anisotropy (FA), individual differences in tract microstructure. In Experiment 1, participants completed the Reading the Mind in the Eyes Task (RMET), a well-validated assay of facial expression decoding. In Experiment 2, a different set of participants completed the RMET, plus an odd-emotion-out task of facial emotion discrimination. In both experiments, participants also completed a control odd-identity-out facial identity discrimination task. In Experiment 1, FA of the right-, but not the left-hemisphere, UF was significantly correlated with performance on the RMET task, specifically for emotional, but not neutral expressions. UF FA was not significantly correlated with facial identity discrimination performance. In Experiment 2, FA of the right-, but not left-hemisphere, UF was again significantly correlated with performance on emotional items from the RMET, together with performance on the facial emotion discrimination task. Again, no significant association was found between UF FA and facial identity discrimination performance. Our findings highlight the contribution of right-hemisphere UF microstructure to inter-individual variability in the ability to decode facial emotion expressions, and may explain why disruption of this pathway affects social behaviour.