Arterial stiffness and white matter integrity in the elderly: A diffusion tensor and magnetization transfer imaging study.

BACKGROUND AND PURPOSE: The stiffness of large arteries and increased pulsatility can have an impact on the brain white matter (WM) microstructure, however those mechanisms are still poorly understood. The aim of this study was to investigate the association between central artery stiffness, axonal and myelin integrity in 54 cognitively unimpaired elderly subjects (65-75 years old). METHODS: The neuronal fiber integrity of brain WM was assessed using diffusion tensor metrics and magnetization transfer imaging as measures of axonal organization (Fractional anisotropy, Radial diffusivity) and state of myelination (Myelin volume fraction). Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Statistical analyses included 4 regions (the corpus callosum, the internal capsule, the corona radiata and the superior longitudinal fasciculus) which have been previously denoted as vulnerable to increased central artery stiffness. RESULTS: cfPWV was significantly associated with fractional anisotropy and radial diffusivity (p < 0.05, corrected for multiple comparisons) but not with myelin volume fraction. Findings from this study also show that improved executive function performance correlates with Fractional anisotropy positively (p < 0.05 corrected) as well as with myelin volume fraction and radial diffusivity negatively (p < 0.05 corrected). CONCLUSIONS: These findings suggest that arterial stiffness is associated with axon degeneration rather than demyelination. Controlling arterial stiffness may play a role in maintaining the health of WM axons in the aging brain.

A semi-immersive virtual reality incremental swing balance task activates prefrontal cortex: a functional near-infrared spectroscopy study.

Previous functional near-infrared spectroscopy (fNIRS) studies indicated that the prefrontal cortex (PFC) is involved in the maintenance of the postural balance after external perturbations. So far, no studies have been conducted to investigate the PFC hemodynamic response to virtual reality (VR) tasks that could be adopted in the field of functional neurorehabilitation. The aim of this fNIRS study was to assess PFC oxygenation response during an incremental and a control swing balance task (ISBT and CSBT, respectively) in a semi-immersive VR environment driven by a depth-sensing camera. It was hypothesized that: i) the PFC would be bilaterally activated in response to the increase of the ISBT difficulty, as this cortical region is involved in the allocation of attentional resources to maintain postural control; and ii) the PFC activation would be greater in the right than in the left hemisphere considering its dominance for visual control of body balance. To verify these hypotheses, 16 healthy male subjects were requested to stand barefoot while watching a 3 dimensional virtual representation of themselves projected onto a screen. They were asked to maintain their equilibrium on a virtual blue swing board susceptible to external destabilizing perturbations (i.e., randomizing the forward-backward direction of the impressed pulse force) during a 3-min ISBT (performed at four levels of difficulty) or during a 3-min CSBT (performed constantly at the lowest level of difficulty of the ISBT). The center of mass (COM), at each frame, was calculated and projected on the floor. When the subjects were unable to maintain the COM over the board, this became red (error). After each error, the time required to bring back the COM on the board was calculated (returning time). An eight-channel continuous wave fNIRS system was employed for measuring oxygenation changes (oxygenated-hemoglobin, O2Hb; deoxygenated-hemoglobin, HHb) related to the PFC activation (Brodmann Areas 10, 11 and 46). The results have indicated that the errors increased between the first and the second level of difficulty of the ISBT, then decreased and remained constant; the returning time progressively increased during the first three levels of difficulty and then remained constant. During the CSBT, the errors and the returning time did not change. In the ISBT, the increase of the first three levels of difficulty was accompanied by a progressive increase in PFC O2Hb and a less consistent decrease in HHb. A tendency to plateau was observable for PFC O2Hb and HHb changes in the fourth level of difficulty of the ISBT, which could be partly explained by a learning effect. A right hemispheric lateralization was not found. A lower amplitude of increase in O2Hb and decrease in HHb was found in the PFC in response to the CSBT with respect to the ISBT. This study has demonstrated that the oxygenation increased over the PFC while performing an ISBT in a semi-immersive VR environment. These data reinforce the involvement of the PFC in attention-demanding balance tasks. Considering the adaptability of this virtual balance task to specific neurological disorders, the absence of motion sensing devices, and the motivating/safe semi-immersive VR environment, the ISBT adopted in this study could be considered valuable for diagnostic testing and for assessing the effectiveness of functional neurorehabilitation.

Sexually dimorphic brain volume interaction in college-aged binge drinkers.

BACKGROUND: Binge consumption of alcohol is a major societal problem associated with important cognitive, physiological and neurotoxic consequences. Converging evidence highlights the need to assess binge drinking (BD) and its effects on the developing brain while taking into account gender differences. Here, we compared the brain volumetric differences between genders in college-aged binge drinkers and healthy volunteers. METHOD: T1-weighted magnetic resonance imaging (MRI) images of 30 binge drinkers (18 males) and 46 matched healthy volunteers (23 males) were examined using voxel-based morphometry. The anatomical scans were covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Whole brain voxel-wise group comparisons were performed using a cluster extent threshold correction. RESULTS: Several large clusters qualified with group-by-gender interactions were observed in prefrontal, striatal and medial temporal areas, whereby BD females had more volume than non-BD females, while males showed the inverse pattern of decreased volume in BD males and increased volume in non-BD males. AUDIT scores negatively correlated with volume in the right superior frontal cortex and precentral gyrus. CONCLUSIONS: These findings dovetail with previous studies reporting that a state effect of BD in college-aged drinkers and the severity of alcohol use are associated with volumetric alterations in the cortical and subcortical areas of the brain. Our study indicates that these widespread volumetric changes vary differentially by gender, suggesting either sexual dimorphic endophenotypic risk factors, or differential neurotoxic sensitivities for males and females.

ApoE4 effects on automated diagnostic classifiers for mild cognitive impairment and Alzheimer's disease.

Biomarkers are the only feasible way to detect and monitor presymptomatic Alzheimer's disease (AD). No single biomarker can predict future cognitive decline with an acceptable level of accuracy. In addition to designing powerful multimodal diagnostic platforms, a careful investigation of the major sources of disease heterogeneity and their influence on biomarker changes is needed. Here we investigated the accuracy of a novel multimodal biomarker classifier for differentiating cognitively normal (NC), mild cognitive impairment (MCI) and AD subjects with and without stratification by ApoE4 genotype. 111 NC, 182 MCI and 95 AD ADNI participants provided both structural MRI and CSF data at baseline. We used an automated machine-learning classifier to test the ability of hippocampal volume and CSF Aß, t-tau and p-tau levels, both separately and in combination, to differentiate NC, MCI and AD subjects, and predict conversion. We hypothesized that the combined hippocampal/CSF biomarker classifier model would achieve the highest accuracy in differentiating between the three diagnostic groups and that ApoE4 genotype will affect both diagnostic accuracy and biomarker selection. The combined hippocampal/CSF classifier performed better than hippocampus-only classifier in differentiating NC from MCI and NC from AD. It also outperformed the CSF-only classifier in differentiating NC vs. AD. Our amyloid marker played a role in discriminating NC from MCI or AD but not for MCI vs. AD. Neurodegenerative markers contributed to accurate discrimination of AD from NC and MCI but not NC from MCI. Classifiers predicting MCI conversion performed well only after ApoE4 stratification. Hippocampal volume and sex achieved AUC = 0.68 for predicting conversion in the ApoE4-positive MCI, while CSF p-tau, education and sex achieved AUC = 0.89 for predicting conversion in ApoE4-negative MCI. These observations support the proposed biomarker trajectory in AD, which postulates that amyloid markers become abnormal early in the disease course while markers of neurodegeneration become abnormal later in the disease course and suggests that ApoE4 could be at least partially responsible for some of the observed disease heterogeneity.

Associations between white matter microstructure and amyloid burden in preclinical Alzheimer's disease: A multimodal imaging investigation.

Some cognitively healthy individuals develop brain amyloid accumulation, suggestive of incipient Alzheimer's disease (AD), but the effect of amyloid on other potentially informative imaging modalities, such as Diffusion Tensor Imaging (DTI), in characterizing brain changes in preclinical AD requires further exploration. In this study, a sample (N = 139, mean age 60.6, range 46 to 71) from the Wisconsin Registry for Alzheimer's Prevention (WRAP), a cohort enriched for AD risk factors, was recruited for a multimodal imaging investigation that included DTI and [C-11]Pittsburgh Compound B (PiB) positron emission tomography (PET). Participants were grouped as amyloid positive (Aß+), amyloid indeterminate (Aßi), or amyloid negative (Aß-) based on the amount and pattern of amyloid deposition. Regional voxel-wise analyses of four DTI metrics, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), and radial diffusivity (Dr), were performed based on amyloid grouping. Three regions of interest (ROIs), the cingulum adjacent to the corpus callosum, hippocampal cingulum, and lateral fornix, were selected based on their involvement in the early stages of AD. Voxel-wise analysis revealed higher FA among Aß+ compared to Aß- in all three ROIs and in Aßi compared to Aß- in the cingulum adjacent to the corpus callosum. Follow-up exploratory whole-brain analyses were consistent with the ROI findings, revealing multiple regions where higher FA was associated with greater amyloid. Lower fronto-lateral gray matter MD was associated with higher amyloid burden. Further investigation showed a negative correlation between MD and PiB signal, suggesting that Aß accumulation impairs diffusion. Interestingly, these findings in a largely presymptomatic sample are in contradistinction to relationships reported in the literature in symptomatic disease stages of Mild Cognitive Impairment and AD, which usually show higher MD and lower FA. Together with analyses showing that cognitive function in these participants is not associated with any of the four DTI metrics, the present results suggest an early relationship between PiB and DTI, which may be a meaningful indicator of the initiating or compensatory mechanisms of AD prior to cognitive decline.

Developmental changes in hippocampal shape among preadolescent children.

It is known that the largest developmental changes in the hippocampus take place during the prenatal period and during the first two years of postnatal life. Few studies have been conducted to address the normal developmental trajectory of the hippocampus during childhood. In this study shape analysis was applied to study the normal developing hippocampus in a group of 103 typically developing 6- to 10-year-old preadolescent children. The individual brain was normalized to a template, and then the hippocampus was manually segmented and further divided into the head, body, and tail sub-regions. Three different methods were applied for hippocampal shape analysis: radial distance mapping, surface-based template registration using the robust point matching (RPM) algorithm, and volume-based template registration using the Demons algorithm. All three methods show that the older children have bilateral expanded head segments compared to the younger children. The results analyzed based on radial distance to the centerline were consistent with those analyzed using template-based registration methods. In analyses stratified by sex, it was found that the age-associated anatomical changes were similar in boys and girls, but the age-association was strongest in girls. Total hippocampal volume and sub-regional volumes analyzed using manual segmentation did not show a significant age-association. Our results suggest that shape analysis is sensitive to detect sub-regional differences that are not revealed in volumetric analysis. The three methods presented in this study may be applied in future studies to investigate the normal developmental trajectory of the hippocampus in children. They may be further applied to detect early deviations from the normal developmental trajectory in young children for evaluating susceptibility for psychopathological disorders involving hippocampus.