Biomedical subjects

Jeffrey Browndyke

Publications and source records attributed to Jeffrey Browndyke.

4 recordsLinked to original sources

PubMed2006

Strategies for dissecting genetic-environmental interactions in neurodegenerative disorders.

Complex genetic and environmental interactions contribute to abnormal aging and neurodegenerative disorders. We present information from a series of 1136 consecutive patients presenting with cognitive disorders and show possible significant contribution of toxic environmental and occupational exposures to pathological aging (21% of patients) and interactions of these exposures with common polymorphisms that affect cell injury and inflammation. Such exposures may lower age of onset to same degree as APOE4/4. Common polymorphisms in apolipoprotein E (APOE), hemochromatosis gene (Hfe) and alpha-1-antitrypsin (AAT) are present in up to 40+% of patients and may partially account for differences in clinical syndrome, age of onset and rate of progression. Strategies for the study of these disorders must also consider the role and treatment of common co-morbid illnesses such as alcohol use, nutritional deficiencies, sleep disorders, and pre-existing affective disorder. APOE, Hfe, and AAT genes are expressed in liver tissue and in macrophages and are involved in the host innate immune response to stress, inflammation and infections. Hfe and AAT are involved in iron metabolism and their polymorphisms may contribute to hepatosteatosis and altered homeostasis of lipids (role of APOE), iron, and trace minerals. Some of these responses may be adaptive. Hfe and AAT modulate the apparent effects of toxic exposures on age of onset and progression rate. C282Y polymorphism paradoxically reverses APOE4/4 effect on age of onset. S and Z AAT polymorphisms may attenuate earlier age of onset in persons with toxic or environmental exposure. AAT S or Z polymorphisms are present in 25% of persons with anxiety disorder and 42% of persons with bipolar disorder compared to 10% of control group without pre-existing affective disorder. Common genetic polymorphisms that affect the response to inflammation and cell injury provide a beginning strategy for dissecting neurodegenerative disorders. The effects of APOE, Hfe, and AAT on glucose, lipid, iron and trace mineral homeostasis may affect normal development and aging of the nervous system in addition to their effects on outcome of toxic environmental and occupational exposures and susceptibility and outcome of neurodegenerative illnesses.

Adult↗

PubMed2005

Progressive morphometric and cognitive changes in vascular dementia.

Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.

Aged↗

PubMed2004

Neuropsychological and emotional changes during simulated microgravity: effects of triiodothyronine alendronate, and testosterone.

INTRODUCTION: We present the results of a two-experiment study designed to evaluate the neurocognitive and psychological effects of six-degree head-down bedrest and pharmacologic interventions (3,5,3'-triiodothyronine; T3) implemented to enhance the muscle and bone atrophy associated with simulated microgravity. Subsequently, the effects of countermeasures (alendronate and testosterone) administered to retard or reverse these T3 plus bedrest enhanced atrophic changes, were evaluated. Each participant was tested weekly for 5 weeks during Bedrest or non-bedrest (Up) conditions with the Neurobehavioral Evaluation System 2 (NES2), the Symptom Check List 90 Revised (SCL-90-R), and the Coping Responses Inventory (CRI). Resultant data were subjected to repeated measures, between groups analysis of variance testing for all 82 neurocognitive and psychological test measures. RESULTS: In Experiment 1, participants in the Placebo-Bedrest condition performed better on several neurocognitive measures compared to participants in the T3-Up condition. However, participants in the Placebo-Bedrest condition also reported more confusion. In Experiment 2 (countermeasure trials), superior coordination was observed for participants in the Testosterone-T3 condition over those in the Alendronate-T3 condition, but just the opposite for reaction time. Also, testosterone and to a lesser degree, alendronate, were associated with less self-reported emotional distress than T3 plus bedrest alone. CONCLUSION: Triiodothyronine, alendronate, and testosterone each influence participant response to simulated microgravity. Between group differences for significant findings were substantial and averaged 1.62 standard deviations. Although the observed neurocognitive effects likely pose no immediate danger for research participants, the significantly greater level of self-reported psychological symptoms by T3-Placebo and Placebo-Bedrest treated participants is of clinical importance.

Adult↗

PubMed2002

Applications of computer-based neuropsychological assessment.

OBJECTIVES: To present current applications of computer-based neuropsychological assessment, including the assessment of sports-related concussion, symptom validity testing, and the remote administration of tests through the Internet. PROBLEM AREAS: If computer-based assessment benefits are to become popularized, a few issues will need to be addressed: the development of psychometric data based on comparisons with long-standing empirically sound test measures; additional validation of measures by parties not involved in their commercial development; increased focus on ecological validity; exploration of the usefulness of remote data storage and automated posting to databases; and improved documentation of specific computer hardware and software used in experimental methods. CONCLUSIONS: Beyond ease of administration and data collection, computer-based assessment offers benefits over paper-and-pencil measures in the form of millisecond timing accuracy, reliable and randomized presentation of stimuli over multiple trials and repeat administrations, and unobtrusive measurement of cognitive skills and response times during all aspects of the assessment process.

Brain Injuries↗