A canine model of human aging and Alzheimer's disease

AbstractThe aged dog naturally develops cognitive decline in many different domains (including learning and memory) but also exhibits human-like individual variability in the aging process. The neurobiological basis for cognitive dysfunction may be related to structural changes that reflect neurodegeneration. Molecular cascades that contribute to degeneration in the aging dog brain include the progressive accumulation of beta-amyloid (Aβ) in diffuse plaques and in the cerebral vasculature. In addition, neuronal dysfunction occurs as a consequence of mitochondrial dysfunction and cumulative oxidative damage. In combination, the aged dog captures key features of human aging, making them particularly useful for the development of preventive or therapeutic interventions to improve aged brain function. These interventions can then be translated into human clinical trials. This article is part of a Special Issue entitled: Animal Models of Disease

Assessing Seatbelt Usage among Teenagers in Rural Settings: The Drive Alive Program

Working to increase seatbelt usage among teenagers in rural settings: The Drive Alive Program (Under the direction of Dr. Monica Swahn) Background: Motor vehicle crashes are a leading cause of death in the United States. Teens are less likely to wear seatbelts than other age groups and more likely to be involved in a crash. The Drive Alive program was designed to improve seatbelt usage among teens. Purpose: This analysis aims to evaluate seatbelt use among teen drivers in a rural setting. Specifically, are there differences between males and females in terms of seatbelt use? Are drivers more likely to wear their seatbelts than passengers? Methods: Data was gathered from observational surveys (N= 3,743). Surveys were gathered by trained observers in South Georgia from 2010-2011. Records were analyzed in SPSS using three categories: occupant, sex, and belt use. The null hypotheses for this study are: 1) there is no significant difference between male and female drivers or passengers in seatbelt usage; and, 2) there is no significant difference between driver and passenger seatbelt usage. Results: Descriptive analyses were computed to determine average seatbelt use across all occupants. Chi Square for Independence tests were computed to determine differences between drivers and passengers and males and females. Females were significantly more likely than males to wear their seatbelt (Females, 70%; Males, 59%). There were no significant differences in seatbelt use for drivers and their passengers. Conclusions: Results for females being more likely to wear seatbelts is consistent with the literature. Future research might include comparison between schools with different versions of the program. Programs to increase seatbelt usage among teens should include parents, education, enforcement, teen-led activities, and partnership with educators and community organizations. Save the lives of young drivers by modeling seatbelt wearing, appropriately implementing comprehensive seatbelt use improvement programs, and enforcing the law. These simple measures will improve seatbelt use and reduce roadway fatalities

The Impact of the Gradual Release of Responsibility Professional Development on Teacher Self-Efficacy

The purpose of this study was to determine the impact of the Gradual Release of Responsibility instructional framework professional development on teacher self-efficacy and the perception of its impact on student achievement. The scope of this study was a qualitative study including focus group interviews and open-ended question responses of teachers and administrators who had participated in the professional development in a rural district in the foothills of North Carolina. The methodology included focus group interviews and coding the responses from the open-ended professional development questions. The findings include teacher quotes from the transcriptions of the interviews as supporting the research found in the literature on high-quality professional development and the components of the Gradual Release of Responsibility. The conclusion reached was that teacher self-efficacy was increased in implementing the framework, and many teachers believed the implementation has increased student achievement. Limitations of this study included the researcher acted as the interviewer; the researcher was the professional development developer and deliverer. This study contributes to the information which could be useful for district and school administrators when planning for high-quality professional development for continuous school improvement

Antioxidants in the canine model of human aging

AbstractOxidative damage can lead to neuronal dysfunction in the brain due to modifications to proteins, lipids and DNA/RNA. In both human and canine brain, oxidative damage progressively increases with age. In the Alzheimer's disease (AD) brain, oxidative damage is further exacerbated, possibly due to increased deposition of beta-amyloid (Aβ) peptide in senile plaques. These observations have led to the hypothesis that antioxidants may be beneficial for brain aging and AD. Aged dogs naturally develop AD-like neuropathology (Aβ) and cognitive dysfunction and are a useful animal model in which to test antioxidants. In a longitudinal study of aging beagles, a diet rich in antioxidants improved cognition, maintained cognition and reduced oxidative damage and Aβ pathology in treated animals. These data suggest that antioxidants may be beneficial for human brain aging and for AD, particularly as a preventative intervention. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease

Con: Are We Ready to Translate Alzheimer\u27s Disease-Modifying Therapies to People with Down Syndrome?

BACKGROUND: Adults with Down syndrome develop Alzheimer\u27s disease neuropathology in an age-dependent manner. This unique feature provides an opportunity to test interventions targeted for prevention of Alzheimer\u27s disease neuropathology and dementia in Down syndrome. DISCUSSION: In considering clinical trial designs, however, there are several challenges that we believe will be critical to examine further. These include: accuracy in dementia, mild cognitive impairment and preclinical Alzheimer\u27s disease diagnoses in Down syndrome; clinical trial outcome measures appropriate for individuals with Down syndrome; in vivo imaging outcome measures (and practical considerations); and contributions of medical co-morbidities to disease progression. Also, when studies are designed, the molecular target may appear to be obvious (for example, targeting beta-amyloid pathology), but chromosome 21 has over 200 additional genes that could influence both positive and negative clinical trial outcomes. SUMMARY: Observational longitudinal studies of aging in Down syndrome will be critically important as there is a need to establish sensitive clinical outcome measures and understand the consequences of gene overexpression in relation to specific interventions

Jet of Blood VR: First Playable Demo

A VR staging of Anonin Artaud’s 1925 surrealist play, Jet of Blood. The project experiments with virtual reality as a means to reimagine performance and frame the player, the audience, as actor. Ideas from Artaud’s philosophy such as the Theatre of Cruelty are incorporated along with spatial storytelling and game design. The project also seeks to expand accessibility to deaf and hard of hearing audiences through use of particle and text effects to visually express audio and sound

Brain-Blood Partition Coefficient and Cerebral Blood Flow in Canines Using Calibrated Short TR Recovery (CaSTRR) Correction Method.

The brain-blood partition coefficient (BBPC) is necessary for quantifying cerebral blood flow (CBF) when using tracer based techniques like arterial spin labeling (ASL). A recent improvement to traditional MRI measurements of BBPC, called calibrated short TR recovery (CaSTRR), has demonstrated a significant reduction in acquisition time for BBPC maps in mice. In this study CaSTRR is applied to a cohort of healthy canines (n = 17, age = 5.0 - 8.0 years) using a protocol suited for application in humans at 3T. The imaging protocol included CaSTRR for BBPC maps, pseudo-continuous ASL for CBF maps, and high resolution anatomical images. The standard CaSTRR method of normalizing BBPC to gadolinium-doped deuterium oxide phantoms was also compared to normalization using hematocrit (Hct) as a proxy value for blood water content. The results show that CaSTRR is able to produce high quality BBPC maps with a 4 min acquisition time. The BBPC maps demonstrate significantly higher BBPC in gray matter (0.83 ± 0.05 mL/g) than in white matter (0.78 ± 0.04 mL/g, p = 0.006). Maps of CBF acquired with pCASL demonstrate a negative correlation between gray matter perfusion and age (p = 0.003). Voxel-wise correction for BBPC is also shown to improve contrast to noise ratio between gray and white matter in CBF maps. A novel aspect of the study was to show that that BBPC measurements can be calculated based on the known Hct of the blood sample placed in scanner. We found a strong correlation (R 2 = 0.81 in gray matter, R 2 = 0.59 in white matter) established between BBPC maps normalized to the doped phantoms and BBPC maps normalized using Hct. This obviates the need for doped water phantoms which simplifies both the acquisition protocol and the post-processing methods. Together this suggests that CaSTRR represents a feasible, rapid method to account for BBPC variability when quantifying CBF. As canines have been used widely for aging and Alzheimer's disease studies, the CaSTRR method established in the animals may further improve CBF measurements and advance our understanding of cerebrovascular changes in aging and neurodegeneration

Jet of Blood

A virtual production of Antonin Artaud’s 1925 play, Jet of Blood

Metabolic and Vascular Imaging Biomarkers in Down Syndrome Provide Unique Insights Into Brain Aging and Alzheimer Disease Pathogenesis

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD). Neuropathology consistent with AD is present by 40 years of age and dementia may develop up to a decade later. In this review, we describe metabolic and vascular neuroimaging studies in DS that suggest these functional changes are a key feature of aging, linked to cognitive decline and AD in this vulnerable cohort. FDG-PET imaging in DS suggests systematic reductions in glucose metabolism in posterior cingulate and parietotemporal cortex. Magentic resonance spectroscopy studies show consistent decreases in neuronal health and increased myoinositol, suggesting inflammation. There are few vascular imaging studies in DS suggesting a gap in our knowledge. Future studies would benefit from longitudinal measures and combining various imaging approaches to identify early signs of dementia in DS that may be amenable to intervention