Multimodal analysis in normal aging, mild cognitive impairment, and Alzheimer's disease: group differentiation, baseline cognition, and prediction of future cognitive decline

Thesis (Ph.D.)--Boston UniversityAlzheimer's disease (AD) is a progressive neurodegenerative disease with an insidious onset that makes it difficult to distinguish from normal aging. It begins with an impairment of memory that develops into amnestic mild cognitive impairment (aMCI) and later to dementia as deficits become apparent in other cognitive domains. Effective biomarkers that differentiate normal aging, MCI, and AD and predict future cognitive decline are needed. Potential biomarkers have been studied in isolation, but their impact when combined is not understood. The goal of this project is to determine the optimal combination of CSF biomarkers, MRI morphometry, FDG PET metabolism, and neuropsychological test scores to differentiate between normal aging subjects and those with MCI and AD. This study addresses: 1) the optimal normalization region and partial volume correction method to quantify FDG PET analysis, 2) the effects of adjusting MRI-based cortical thickness measures for differences in gray/white matter tissue contrast in normal aging and disease, 3) whether multimodal multivariate stepwise logistic regression models can predict group membership, and 4) whether multimodal multivariate stepwise linear regression models can determine which imaging and CSF biomarker variables best predict future cognitive decline. The results indicate that normalizing FDG PET to the cerebellum along with using a gray matter mask for partial volume correction provides optimal prediction. In contrast, age-associated changes in gray/white matter intensity ratio did not differentiate between the groups and only slightly improved the efficacy of cortical thickness as a biomarker. MRI morphometry of the gray matter and neuropsychological test scores were better able to discriminate between the groups than FDG PET or CSF biomarker concentrations. Combining all modalities significantly improved the index of discrimination, especially at the earliest stages of the disease. MRI gray matter morphometry variables were more highly associated with baseline cognitive function and best predicted future cognitive decline compared to other variables. Overall these findings demonstrate that a multimodal approach using MRI morphometry, FDG PET metabolism, neuropsychological test scores, and CSF biomarkers provides significantly better discrimination than any modality alone. Hence, the variables important for discriminating between the groups may be candidates for biomarkers in human clinical interventional trials

Scars of War

Scars of War: The Psychological and Physical Traumas of War Depicted through Art.War is shattering, leaving behind gaping wounds in need of healing. Some require bandages, other wounds are psychological and not visible. Both leave a scar. These scars are an inevitable part of the human experience. The psychological and physical ramifications of war exist as long as strife pervades. This collection of works, depicting war from the French Revolution to present day Iraq, illustrates the scarring impact war has on the people and places within its grasp. New technology and art styles have transformed the way we see the world. We go from plate etchings in the earliest works to works responding to the impact of televised images during the Vietnam War, and photographs and abstract art responding to the recent conflicts in Afghanistan and Iraq. Regardless of what way artists choose to depict war, war remains heartbreaking, psychologically and physically destructive, leaving an imprint on the world around us

Werbenutzen einer unterhaltenden Website : eine Untersuchung am Beispiel der Moorhuhnjagd

Jedes Jahr steigt die Zahl der Internet-Nutzer, in Deutschland sind es mittlerweile 19,5 Millionen. Als Konsequenz können immer mehr Menschen von Unternehmen über das Internet erreicht werden. Das Schlagwort des e-Commerce beherrscht die Diskussion. Aber auch Unternehmen, die das Internet nicht als Handelsplattform verwenden, sind im Internet mit eigenen Homepages präsent. Sie nutzen es zur Kommunikationspolitik. Dabei ist bei zu Werbezwecken designten Homepages der werbliche Kommunikationsprozess im Vergleich zu den klassischen Medien umgedreht. Der User wird nicht passiv von einem Unternehmen mit Werbung "berieselt", sondern muss eine Seite aktiv aufrufen. Dies tut er nur, wenn er sich hiervon einen Nutzen verspricht. Im Fall von High-Involvement Produkten zieht er einen Informationsnutzen aus einer entsprechend informativen Homepage. Bei Low-Involvement Produkten sucht der Konsument nicht nach Informationen. Er besucht eine Homepage nur, wenn er einen Unterhaltungsnutzen erwartet. Wechselt man die Perspektive vom Nachfrager zum Anbieter, stellt sich die bis dato noch nicht durch eine empirische Untersuchung beantwortete Frage, was für Vorteile ein Unternehmen aus der Bereitstellung einer unterhaltenden Werbe­homepage ziehen kann. Als relevante Werbeziele wurden die Steigerung der aktiven Markenbekanntheit, die Veränderung des Image, der Aufbau neuer und lebendiger Markenbilder sowie eine Erhöhung der Kaufabsicht untersucht. Um Veränderungen nachweisen zu können, wurden zwei Gruppen befragt. Eine Gruppe hatte das Internet-Spiel Moorhuhnjagd von Johnnie Walker, das als beispielhafter Inhalt einer unterhaltenden Werbehomepage gelten kann, gespielt, die andere nicht. Spieler nehmen das Image dieser Marke signifikant trendgemäßer wahr und haben lebendigere innere Bilder zu Johnnie Walker als Nicht-Spieler. Das Moorhuhn konnte innerhalb kurzer Zeit als neues Markenbild etabliert werden

Seed Location Impacts Whole-Brain Structural Network Comparisons between Healthy Elderly and Individuals with Alzheimer’s Disease

Whole-brain networks derived from diffusion tensor imaging (DTI) data require the identification of seed and target regions of interest (ROIs) to assess connectivity patterns. This study investigated how initiating tracts from gray matter (GM) or white matter (WM) seed ROIs impacts (1) structural networks constructed from DTI data from healthy elderly (control) and individuals with Alzheimer’s disease (AD) and (2) between-group comparisons using these networks. DTI datasets were obtained from the Alzheimer’s disease Neuroimaging Initiative database. Deterministic tractography was used to build two whole-brain networks for each subject; one in which tracts were initiated from WM ROIs and another in which they were initiated from GM ROIs. With respect to the first goal, in both groups, WM-seeded networks had approximately 400 more connections and stronger connections (as measured by number of streamlines per connection) than GM-seeded networks, but shared 94% of the connections found in the GM-seed networks. With respect to the second goal, between-group comparisons revealed a stronger subnetwork (as measured by number of streamlines per connection) in controls compared to AD using both WM-seeded and GM-seeded networks. The comparison using WM-seeded networks produced a larger (i.e., a greater number of connections) and more significant subnetwork in controls versus AD. Global, local, and nodal efficiency were greater in controls compared to AD, and between-group comparisons of these measures using WM-seeded networks had larger effect sizes than those using GM-seeded networks. These findings affirm that seed location significantly affects the ability to detect between-group differences in structural networks

Impairment of Bone Health in Pediatric Patients with Hemolytic Anemia

Introduction Sickle cell anemia and thalassemia result in impaired bone health in both adults and youths. Children with other types of chronic hemolytic anemia may also display impaired bone health. Study Design To assess bone health in pediatric patients with chronic hemolytic anemia, a cross-sectional study was conducted involving 45 patients with different forms of hemolytic anemia (i.e., 17 homozygous sickle cell disease and 14 hereditary spherocytosis patients). Biochemical, radiographic and anamnestic parameters of bone health were assessed. Results Vitamin D deficiency with 25 OH-vitamin D serum levels below 20 ng/ml was a common finding (80.5%) in this cohort. Bone pain was present in 31% of patients. Analysis of RANKL, osteoprotegerin (OPG) and osteocalcin levels indicated an alteration in bone modeling with significantly elevated RANKL/OPG ratios (control: 0.08+0.07; patients: 0.26+0.2, P = 0.0007). Osteocalcin levels were found to be lower in patients compared with healthy controls (68.5+39.0 ng/ml vs. 118.0+36.6 ng/ml, P = 0.0001). Multiple stepwise regression analysis revealed a significant (P<0.025) influence of LDH (partial r2 = 0.29), diagnosis of hemolytic anemia (partial r2 = 0.05) and age (partial r2 = 0.03) on osteocalcin levels. Patients with homozygous sickle cell anemia were more frequently and more severely affected by impaired bone health than patients with hereditary spherocytosis. Conclusion Bone health is impaired in pediatric patients with hemolytic anemia. In addition to endocrine alterations, an imbalance in the RANKL/OPG system and low levels of osteocalcin may contribute to this impairment

Cerebral versus Ocular Visual Impairment: The Impact on Developmental Neuroplasticity

Cortical/cerebral visual impairment (CVI) is clinically defined as significant visual dysfunction caused by injury to visual pathways and structures occurring during early perinatal development. Depending on the location and extent of damage, children with CVI often present with a myriad of visual deficits including decreased visual acuity and impaired visual field function. Most striking, however, are impairments in visual processing and attention which have a significant impact on learning, development, and independence. Within the educational arena, current evidence suggests that strategies designed for individuals with ocular visual impairment are not effective in the case of CVI. We propose that this variance may be related to differences in compensatory neuroplasticity related to the type of visual impairment, as well as underlying alterations in brain structural connectivity. We discuss the etiology and nature of visual impairments related to CVI, and how advanced neuroimaging techniques (i.e., diffusion-based imaging) may help uncover differences between ocular and cerebral causes of visual dysfunction. Revealing these differences may help in developing future strategies for the education and rehabilitation of individuals living with visual impairment