Background: Alzheimer's disease (AD) prevalence has grown 68% in that timeframe, and has risen to the sixth leading cause of death in the United States. Hispanics are at increased risk of acquiring cardiovascular risk factors that contribute to AD pathology and are minimally 1.5 times more likely at any age to be diagnosed with AD. Identifying the roots of this ethnic disparity can lead to more effective personalized health interventions. Aim: To compare indices of vascular health to measures of gray matter integrity in middle-aged Hispanic and Caucasian adults. As a secondary outcome, we will examine these health statuses in relation to cognitive function. Methods: Sixty subjects in Caucasian (n=30) and Hispanic (n=30) groups were matched across racial classification by age, gender, years of education, and cognitive status. Participants' arterial stiffness (carotid-femoral pulse-wave velocity and [beta]-stiffness index), arterial wave reflection (augmentation index), endothelial function (flow-mediated dilation), and atherosclerosis (carotid arterial wall intima-media thickness) were characterized. Magnetic resonance imaging (MRI) estimated cortical thickness in a priori cortical regions of interest known to be susceptible to vascular risk factors. Cognitive function was assessed with a comprehensive cognitive battery covering the domains of global cognitive function, language function, visuo-spatial abilities, memory function and attention-executive function. Results: Carotid-femoral pulse wave velocity (cfPWV) (p=0.02), Carotid artery [beta]-stiffness index (p=0.01), and augmentation index (Aix) (p=0.05) were significantly greater in Hispanics than in Caucasians. Carotid intima-media thickness (IMT) and flow-mediated dilation (FMD) were not different between the groups. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (p=0.04) with concurrently lower language (p=0.02), memory (p=0.03), and attention-executive functioning (p=0.02). Conclusion: Hispanics exhibited significantly greater cfPWV, Aix, and [beta]-stiffness index as well as selective cortical thinning of the LIFG. Additionally, language, working memory and attention-executive domains of cognition were lower in the Hispanic group compared to their age-, gender-, education- and cognitive status-matched Caucasian counterparts. These results may form a basis for future investigations that aim to explain the increased prevalence and earlier onset of symptoms of AD in the Hispanic population through cardiovascular health. / text

Children born prematurely exhibit a broad range of neuroanatomical abnormalities. The aim of this study was to investigate the long-term effects of very preterm birth on brain volume (cortical and subcortical), cortical thickness and surface area. The participants were 25 children born very preterm (<32 weeks gestational age) without significant post-natal medical sequelae and 32 term-born children between 7 and 10 years of age. Neuroanatomical measures were derived from an automated pipeline. The results suggest a pattern of decreased brain volume, surface area and cortical thickness for children born preterm and the relation between subcortical gray volume and total brain volume differed between groups. The cortex was significantly thinner for children born preterm than term-born children in focal regions of the parietal and temporal lobes. Therefore, even without significant postnatal medical sequelae, very preterm children still exhibit structural differences that persist into middle childhood.

Children born prematurely exhibit a broad range of neuroanatomical abnormalities. The aim of this study was to investigate the long-term effects of very preterm birth on brain volume (cortical and subcortical), cortical thickness and surface area. The participants were 25 children born very preterm (<32 weeks gestational age) without significant post-natal medical sequelae and 32 term-born children between 7 and 10 years of age. Neuroanatomical measures were derived from an automated pipeline. The results suggest a pattern of decreased brain volume, surface area and cortical thickness for children born preterm and the relation between subcortical gray volume and total brain volume differed between groups. The cortex was significantly thinner for children born preterm than term-born children in focal regions of the parietal and temporal lobes. Therefore, even without significant postnatal medical sequelae, very preterm children still exhibit structural differences that persist into middle childhood.

Metabolic Syndrome (MetS), the clustering of obesity, high blood pressure, and disordered glucose and lipid/lipoprotein metabolism within a single individual, is associated with poorer cognitive function and dementia in later life. It has been hypothesized that cognitive impairment in MetS occurs primarily within the context of inflammation. MetS risk factors are also associated with thinning of the cerebral cortex. However, the mechanisms by which MetS and inflammation affect the brain are poorly understood. The present study used statistical mediation to examine the relationship between MetS risk factors, cortical thickness in a priori regions of interest (ROIs) and inflammation. ROIs in the inferior frontal, superior temporal, middle frontal, supra marginal, anterior cingulate and middle occipital regions were chosen from the previous literature. Serum levels of pro-inflammatory markers (interleukin 1, interleukin 2, interleukin 6 and C-Reactive Protein) were measured using enzyme-linked immunosorbent assays. Forty-three adults between the ages of 40 and 60 years underwent a health screen, neuropsychological testing and structural magnetic resonance imaging. A higher number of MetS risk factors was associated with thinning in the inferior frontal ROI (β=-0.35, p = 0.019). A higher number of MetS risk factors was also associated with higher levels of serum interleukin 2 (β=0.31, p=0.04). A higher level of serum interleukin 2 was also associated with reduced thickness in the inferior frontal ROI (β=-0.41, p=0.013). After accounting for the effects of interleukin 2, the number of MetS risk factors was no longer associated with cortical thickness in the inferior frontal ROI indicating successful statistical mediation and pointing towards a potentially important role for imflammation in linking MetS to cortical thinning and cognitive vunlerability. / text

L’objectif de ce travail était d’étudier certains aspects de la géométrie ou macroarchitecture afin de mieux comprendre la contribution de la géométrie sur le risque de fracture. Pour les os tubulaires, l’apposition périostée tente de compenser la perte osseuse après la ménopause et il existe peu d’études pour les vertèbres. Dans une étude prospective, les dimensions des corps vertébraux augmentent significativement à 3 ans chez les femmes ménopausées ostéoporotiques et que cette augmentation est fortement associée à la taille initiale des os suggérant que les os plus grands ont besoin d’une expansion périostée plus importante pour maintenir la résistance osseuse. Des études antérieures ont suggéré qu’il fallait évaluer la géométrie du rachis dans sa globalité en étudiant le rôle des courbures rachidiennes. Dans une deuxième étude prospective de 3 ans chez des femmes ménopausées ostéoporotiques, la cyphose thoracique est un facteur de risque de fractures vertébrales même après ajustement sur la présence de fractures vertébrales prévalentes. Une troisième étude prospective qui a cherché à identifier les paramètres géométriques associés au risque de fracture de hanche chez les femmes ménopausées ostéoporotiques non traitées montre que l’épaisseur corticale fémorale mesurée par l’outil HSA (Hip Structural Analysis) améliore la prédiction du risque de fracture de hanche indépendamment de la mesure de la densité minérale osseuse (DMO). L’outil géométrique que nous avons développé pour s’affranchir de l’influence de la DMO montre que l’augmentation de la distance intertrochantérienne est associée à une augmentation du risque de fracture indépendamment de la DMO. En revanche l’outil actuel est peu reproductible pour la mesure de la corticale fémorale. / The aim of the study was to study certain aspects of bone geometry or macroarchitecture to understand better the contribution of bone geometry on the risk of fracture. For tubular bones, periosteal apposition can occur to compensate bone loss after the menopause and there is no data concerning the prospective changes in vertebral body dimensions. In a prospective study of women with postmenopausal osteoporosis, vertebral body dimensions increase over 3 years in women and the bigger bones need more periosteal expansion to maintain bone strength. Previous studies showed that whole spine geometry and especially the spinal curvatures need be evaluated to understand the role of vertebral geometry on the risk of fracture. In a second prospective study in postmenopausal osteoporotic women, thoracic kyphosis is a risk factor for vertebral fractures over 3 years, even after adjusting on presence of prevalent fractures. A third prospective study aimed at identifying the geometric parameters associated with an increase risk of hip fracture in postmenopausal osteoporotic women untreated. Femoral cortical thickness measured by HSA tool (Hip Structural Analysis) is associated with an increase risk of hip fracture, independently of bone mineral density (BMD). The geometrical tool which we developed to eliminate the influence of the BMD shows that increase in the intertrochanteric distance is associated with an increase risk of hip fracture.

Extra-corporeal membrane oxygenation (ECMO) is a life-saving procedure for patients in respiratory or cardiac distress. Prior studies have demonstrated several known risks to the procedure, such as hypoxia, stroke, and other neurological complications (Cheng et al., 2014) that can lead to temporary or permanent deficits in motor abilities, developmental trajectory, academic abilities, and cognition (Glass et al., 1995). Although several studies have investigated morbidity and mortality rates of pediatric ECMO patients, few have looked at cognitive deficits, and even fewer at magnetic resonance imaging in relation to neuropsychological outcome and behavioral, emotional, or social functioning. The aims of this study were to investigate cognitive ability and behavioral functioning in a group of ECMO-treated patients compared to a normative sample, and to examine brain morphometry in hippocampal regions as they relate to cognitive outcome. Participants for this study were recruited from Primary Children's Hospital in Salt Lake City, UT. The total number of participants recruited was 8 (63% female; M age at testing = 16.75, SD = 4.5), and all participants were at least 1 year post-ECMO procedure (M=5.6 years; SD=2.1) for acute respiratory or cardiac illness. Neuropsychological testing was completed using the NIH Toolbox Cognition Battery. Scores were compared to normative data for age to investigate potential impairment in multiple cognitive domains. Each participant and the parent or guardian of minor participants completed brief questionnaires measuring executive functioning, behavior, and social skills, namely The Behavior Rating Inventory of Executive Functioning, The Behavioral Assessment System for Children, Second Edition, and the Social Skills Improvement System Rating Scales. Six of the participants also underwent MR imaging to obtain measures of cortical thickness in the frontal areas of the brain, as well as hippocampal and total intracranial volume. Performance results on the NIH Toolbox Cognition Battery was impaired in over half of the tested individuals who underwent ECMO as children. Attention, executive function, processing speed, and visual memory were well below the expected range for age in the majority of participants. Crystallized intelligence tasks, such as vocabulary, were in the average to above average range for most participants, likely indicating normal baseline functioning. Self- and informant report revealed variable results across participants, with various behavioral, emotional, and social difficulties reported in the group. Bilateral hippocampal volume was positively correlated with scores on tasks of episodic and working memory, though further study with a larger sample and control group is warranted. Preliminary MRI data for cortical thickness and volume of frontal regions are presented. Interpretation of results, limitations, and future directions are discussed.

Prior research has suggested that any cortical volume (CV) abnormalities in Autism Spectrum Disorder (ASD) need to be further explored by examination of the two determinants of CV, that being cortical thickness (CT) and pial surface area (PSA; Murphy, Beecham, Craig, & Ecker, 2011). The current study suggests that the two determinants of CV should be explored even in the presence of null CV findings, if structure-function analyses are significant (i.e., bi-lateral precentral gyrus and neuropsychological motor test) as demonstrated in the current sample (see Duffield et al., 2013). The only significant anatomic finding was reduced CT in the left frontal motor regions (primarily left precentral gyrus), which also corresponded to the only significant relationship between a motor variable (i.e., grooved pegboard test) and motor region-of-interest (ROI) where ASD had a stronger relationship than typically developing controls (TDC; ASD > TDC). Left hemisphere biased CT group differences has been shown to have the highest classification accuracy (i.e., designation of ASD versus TDC) of morphological parameters (Ecker et al., 2010), yet PSA has been shown to have far greater modulation of CV abnormalities. This is particularly true for subthreshold PSA (Ecker et al., 2013). These prior findings are not only consistent with the current motor ROI findings, but also provide an explanatory framework for the functional neuroanatomy of a generally worse left handed performance (i.e., non-dominant hand) for ASD compared to controls in a generally right handed dominant sample (no significant group differences on handedness). The only significant motor ROI finding was in the left hemisphere (i.e., ipsilateral to worse left handed performance), but subthreshold PSA findings in the right precentral were found and likely provide explanatory power of motor performances in the aggregate, despite a lack of significant statistical differences in a specific motor ROI individually.

The cerebral cortex is gray matter tissue which covers cerebral hemispheres. In recent years, many studies reported that abnormal cortical thickness was found in several diseases of central neural system, such as multiple sclerosis, Alzheimer's diseases, and schizophrenia. Therefore, the whole-brain measurement of cortical thickness using the non-invasive magnetic resonance imaging becomes important. However, not many algorithms were reported in the past due to the extremely complex folding structure of human cortex. In this thesis, a voxel-based cortical thickness method proposed by Hutton et al was implemented using MATLAB to achieve automated measurement. Several crucial factors, including the definition of boundary condition, interpolation method, the step size of developing each streamline, and spatial resolution of imaging space, in the implementation were discussed. In addition, the analysis of stability, or precision, of our self-developed program was evaluated . Sixteen experiments of reproducibility were performed in two months on the same 24-year-old healthy volunteer repeatedly to obtain whole-brain 3D T1WI. Cortical thickness map was calculated independently and normalized to the same coordination. Mean, standard deviation, and normalized standard deviation of 16 measurements were calculated on every cortical voxel, along with whole-brain mean cortical thickness. Various sizes of 3D smoothing kernel were applied, and the results showed stronger smoothing might help higher precision by the cost of spatial resolution.

Hip fracture is the leading cause of acute orthopaedic hospital admission amongst the elderly, with around a third of patients not surviving one-year post-fracture. Current risk assessment tools ignore cortical bone thinning, a focal structural defect characterizing hip fragility. Cortical thickness can be measured using computed tomography, but this is expensive and involves a significant radiation dose. Dual-energy X-ray absorptiometry (DXA) is the preferred imaging modality for assessing fracture risk, and is used routinely in clinical practice. This thesis proposes two novel methods which measure the cortical thickness of the proximal femur from multi-view DXA scans. First, a data-driven algorithm is designed, implemented and evaluated. It relies on a femoral B-spline template which can be deformed to fit an individual?s scans. In a series of experiments on the trochanteric regions of 120 proximal femurs, the algorithm?s performance limits were established using twenty views in the range 0? ? 171?: estimation errors were 0.00 ? 0.50 mm. In a clinically viable protocol using four views in the range ?20? to 40?, measurement errors were ?0.05 ? 0.54 mm. The second algorithm accomplishes the same task by deforming statistical shape and thickness models, both trained using Principal Component Analysis (PCA). Three training cohorts are used to investigate (a) the estimation efficacy as a function of the diversity in the training set and (b) the possibility of improving performance by building tailored models for different populations. In a series of cross-validation experiments involving 120 femurs, minimum estimation errors were 0.00 ? 0.59 mm and ?0.01 ? 0.61 mm for the twenty- and four-view experiments respectively, when fitting the tailored models. Statistical significance tests reveal that the template algorithm is more precise than the statistical, and that both are superior to a blind estimator which naively assumes the population mean, but only in regions of thicker cortex. It is concluded that cortical thickness measured from DXA is unlikely to assist fracture prediction in the femoral neck and trochanters, but might have applicability in the sub-trochanteric region.

One of the earliest symptoms of Alzheimer’s disease (AD) and age-related cognitive decline is topographical disorientation or impairment to spatial navigation. Furthermore, aging and AD are associated with cortical gray-matter thinning, particularly in the medial temporal and posterior cingulate regions, which have been associated with spatial navigation. Aerobic exercise has been well-established as a beneficial intervention to curtail the neurodegenerative effects of aging. This study aims to explore the relationship between cardiorespiratory fitness (CRF), and two markers of AD and cognitive aging, virtual navigation ability and cortical thickness of the entorhinal, parahippocampal and retrosplenial regions. Cross-sectional data utilized in this study was collected from 23 healthy older adults (60-80 years). Measures included in our analyses consisted of estimated VO2max, T1-weighted structural MR images, and behavioral performance on a virtual navigation task, measured as numbers of objects located during recall. Cortical thickness of the regions of interest (ROIs) was determined by processing T1-weighted MR images in FreeSurfer. We hypothesized that greater CRF would correlate with improved virtual navigation performance and greater cortical thickness of ROIs. Our analyses did not reveal statistically significant relationships between CRF and navigation performance or CRF and cortical thickness. However, Pearson’s correlations found right retrosplenial cortical (RSC) thickness and navigation performance to be significantly related. Multiple regression models of right RSC thickness and navigation performance were performed controlling for age, sex, education and task version. These analyses revealed that greater right RSC thickness predicted navigation performance. Additionally, this model showed that older age predicts decline in navigation performance. Our findings did not survive multiple comparisons correction; nonetheless, the results provide promising insight to the relationship between cortical thickness and navigation performance in healthy aging. Further cross-sectional and longitudinal investigations with a larger sample size are required to assess the impact of CRF and exercise on cortical thickness and navigation abilities in healthy aging. Understanding these relationships would contribute to the expansive body of literature that has linked CRF and exercise to neuroprotective mechanisms in the aging brain.