Medicine and Health Sciences Commons^™

Retention Of Normal Glia Function By An Isoform-Selective Protein Kinase Inhibitor Drug Candidate That Modulates Cytokine Production And Cognitive Outcomes, Zhengqiu Zhou, Adam D. Bachstetter, Claudia B. Späni, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates. Therefore, it is essential that the glial effects of this CNS-active kinase inhibitor be addressed in order to anticipate future use in clinical investigations.

Methods: …

The Poverty Of The Neuroscience Of Poverty: Policy Payoff Or False Promise?, Amy L. Wax

All Faculty Scholarship

A recent body of work in neuroscience examines the brains of people suffering from social and economic disadvantage. This article assesses claims that this research can help generate more effective strategies for addressing these social conditions and their effects. It concludes that the so-called neuroscience of deprivation has no unique practical payoff, and that scientists, journalists, and policy-makers should stop claiming otherwise. Because this research does not, and generally cannot, distinguish between innate versus environmental causes of brain characteristics, it cannot predict whether neurological and behavioral deficits can be addressed by reducing social deprivation. Also, knowledge of brain mechanisms yields …

Caloric Restriction Preserves Memory And Reduces Anxiety Of Aging Mice With Early Enhancement Of Neurovascular Functions, Ishita Parikh, Janet Guo, Kai-Hsiang Chuang, Yu Zhong, Ralf G. Rempe, Jared D. Hoffman, Rachel Armstrong, Björn Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of …

The Tnfα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, And Post-Ischemic Cell Loss, L. Creed Pettigrew, Richard J. Kryscio, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from …

Category Learning In Older Adulthood: A Study Of The Shepard, Hovland, And Jenkins (1961) Tasks., Rahel Rabi, John Paul Minda

Brain and Mind Institute Researchers' Publications

Shepard, Hovland, and Jenkins (1961) examined the categorization abilities of younger adults using tasks involving single-dimensional rule learning, disjunctive rule learning, and family resemblance learning. The current study examined category learning in older adults using this well-known category set. Older adults, like younger adults, found category tasks with a single relevant dimension the easiest to learn. In contrast to younger adults, older adults found complex disjunctive rule-based categories harder to learn than family resemblance based categories. Disjunctive rule-based category learning appeared to be the most difficult for older adults to learn because this category set placed the heaviest demands on …

Prenatal Alcohol And Nicotine Exposure And The Subsequent Cognitive And Behavioral Deficits Seen In Children, Abigail P. Stewart

Senior Honors Theses

Prenatal alcohol and nicotine exposure have well known physiological effects on the fetus. However, it is the goal of this thesis to inform the reader of of the deleterious effects that these substances can have on cognitive and behavioral development in children. A literature review in relation to this topic was conducted through online databases using key words. Though some of the results were inconsistent, enough evidence exists for women to be educated on the increased risks for cognitive and behavioral deficits in children exposed to alcohol and nicotine in utero.

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …

Contemplating Mindfulness At Work: An Integrative Review, Christopher Lyddy, Darren J. Good, Theresa M. Glomb, Joyce E. Bono, Kirk W. Brown, Michelle K. Duffy, Ruth A. Baer, Judson A. Brewer, Sara W. Lazar

School of Business Faculty Publications

Mindfulness research activity is surging within organizational science. Emerging evidence across multiple fields suggests that mindfulness is fundamentally connected to many aspects of workplace functioning, but this knowledge base has not been systematically integrated to date. This review coalesces the burgeoning body of mindfulness scholarship into a framework to guide mainstream management research investigating a broad range of constructs. The framework identifies how mindfulness influences attention, with downstream effects on functional domains of cognition, emotion, behavior, and physiology. Ultimately, these domains impact key workplace outcomes, including performance, relationships, and well-being. Consideration of the evidence on mindfulness at work stimulates important …

Tract-Based Spatial Statistics In Preterm-Born Neonates Predicts Cognitive And Motor Outcomes At 18 Months., E G Duerden, J Foong, V Chau, H Branson, K J Poskitt, R E Grunau, A Synnes, J G Zwicker, S P Miller

Brain and Mind Institute Researchers' Publications

BACKGROUND AND PURPOSE: Adverse neurodevelopmental outcome is common in children born preterm. Early sensitive predictors of neurodevelopmental outcome such as MR imaging are needed. Tract-based spatial statistics, a diffusion MR imaging analysis method, performed at term-equivalent age (40 weeks) is a promising predictor of neurodevelopmental outcomes in children born very preterm. We sought to determine the association of tract-based spatial statistics findings before term-equivalent age with neurodevelopmental outcome at 18-months corrected age.

MATERIALS AND METHODS: Of 180 neonates (born at 24-32-weeks' gestation) enrolled, 153 had DTI acquired early at 32 weeks' postmenstrual age and 105 had DTI acquired later at …

Iodine Status Not Associated With Cognitive Functioning In Older Australians, Li Min Buchanan, Karen E. Charlton, Steven J. Roodenrys, Delia Cocuz, Tammy Pendergast, Gary Ma

Faculty of Science, Medicine and Health - Papers: part A

Objective: This study aims to investigate whether iodine status is associated with cognitive functioning and mood state in a sample of healthy older Australians. Design: Cross-sectional study. Setting: Illawarra region of New South Wales, Australia. Participants: Eighty-four men and women (25 males; 59 females) aged 60-95 years with normal cognitive function. Measurements: Three repeated fasting urine samples were collected a week apart to assess median urinary iodine concentration for the group. Usual dietary iodine intake was measured using an iodine-specific food frequency questionnaire and three repeated 24-hour dietary recalls while nutritional status was assessed using the Mini Nutritional Assessment (MNA). …

Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers Ii: Sigma-2/Pgrmc1 Receptors Mediate Abeta 42 Oligomer Binding And Synaptotoxicity, Nicholas J. Izzo, Jinbin Xu, Chenbo Zeng, Molly J. Kirk, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Gary Look, Gilbert Rishton, Hank Safferstein, Carlos Cruchaga, Alison Goate, Michael A. Cahill, Ottavio Arancio, Robert H. Mach, Rolf Craven, Elizabeth Head, Harry Levine Iii, Tara L. Spires-Jones, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic …

Alzheimer's Therapeutics Targeting Amyloid Beta 1-42 Oligomers I: Abeta 42 Oligomer Binding To Specific Neuronal Receptors Is Displaced By Drug Candidates That Improve Cognitive Deficits, Nicholas J. Izzo, Agnes Staniszewski, Lillian To, Mauro Fa, Andrew F. Teich, Faisal Saeed, Harrison Wostein, Thomas Walko Iii, Anisha Vaswani, Meghan Wardius, Zanobia Syed, Jessica Ravenscroft, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Patricia Finn, Gary Look, Gilbert Rishton, Hank Safferstein, Miles Miller, Conrad Johanson, Edward Stopa, Manfred Windisch, Birgit Hutter-Paier, Mehrdad Shamloo, Ottavio Arancio, Harry Levine Iii, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce …

Effects Of Spending Time Outdoors In Daylight On The Psychosocial Well-Being Of Older People And Their Family Carers: A Systematic Review, Katherine Caldwell, Ritin Fernandez, Victoria Traynor, Cecile Perrin

Faculty of Science, Medicine and Health - Papers: part A

Background: A range of studies found that spending time outdoors in daylight provided substantial benefits for the psychosocial well-being of older people. Good psychosocial well-being is essential in maintaining overall health as people age and often contributes to adequate physical functioning. Objectives: The overall objective of this study was to undertake a systematic review on the effects of spending time outdoors in daylight on the psychosocial well-being of older people and their family carers. Inclusion criteria Types of participants This review considered studies that included older people aged 55 years or more, including those living in a community or residential …

Asymmetrical Interference Effects Between Two-Dimensional Geometric Shapes And Their Corresponding Shape Words, Bradley R. Sturz, Joshua E. Edwards, Ty W. Boyer

Department of Psychology Faculty Publications

Nativists have postulated fundamental geometric knowledge that predates linguistic and symbolic thought. Central to these claims is the proposal for an isolated cognitive system dedicated to processing geometric information. Testing such hypotheses presents challenges due to difficulties in eliminating the combination of geometric and non-geometric information through language. We present evidence using a modified matching interference paradigm that an incongruent shape word interferes with identifying a two-dimensional geometric shape, but an incongruent two-dimensional geometric shape does not interfere with identifying a shape word. This asymmetry in interference effects between two-dimensional geometric shapes and their corresponding shape words suggests that shape …

Decoding The Neural Mechanisms Of Human Tool Use., Jason P Gallivan, D Adam Mclean, Kenneth F Valyear, Jody C Culham

Brain and Mind Institute Researchers' Publications

Sophisticated tool use is a defining characteristic of the primate species but how is it supported by the brain, particularly the human brain? Here we show, using functional MRI and pattern classification methods, that tool use is subserved by multiple distributed action-centred neural representations that are both shared with and distinct from those of the hand. In areas of frontoparietal cortex we found a common representation for planned hand- and tool-related actions. In contrast, in parietal and occipitotemporal regions implicated in hand actions and body perception we found that coding remained selectively linked to upcoming actions of the hand whereas …

Comprehensive Behavioral Characterization Of An App/Ps-1 Double Knock-In Mouse Model Of Alzheimer's Disease, Scott J. Webster, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Despite the extensive mechanistic and pathological characterization of the amyloid precursor protein (APP)/presenilin-1 (PS-1) knock-in mouse model of Alzheimer's disease (AD), very little is known about the AD-relevant behavioral deficits in this model. Characterization of the baseline behavioral performance in a variety of functional tasks and identification of the temporal onset of behavioral impairments are important to provide a foundation for future preclinical testing of AD therapeutics. Here we perform a comprehensive behavioral characterization of this model, discuss how the observed behavior correlates with the mechanistic and pathological observations of others, and compare this model with other commonly used …

Fkbp5 Modulates Attention Bias For Threat: Associations With Hippocampal Function And Morphology, Negar Fani, David Gutman, Erin Tone, Lynn Almli, Kristina B. Mercer, Jennifer Davis, Ebony Glover, Tanja Jovanovic, Bekh Bradley, Ivo D. Dinov, Alen Zamanyan, Arthur W. Toga, Elisabeth B. Binder, Kerry J. Ressler

Psychology Faculty Publications

Context: The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamicpituitary‐adrenal axis functioning, and has been associated with a number of stress‐related psychiatric disorders. The study of intermediate phenotypes, such as emotion‐processing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates psychopathology risk.

Objective: To examine whether allelic variations for a putatively functional SNP associated with FKBP5 gene regulation (rs1360780) would relate differentially to attentional bias for threat; this was measured through behavioral response on a dot probe task and hippocampal activation during task performance. Morphological substrates of differential hippocampal response …

Practice Effects In A Longitudinal, Multi-Center Alzheimer's Disease Prevention Clinical Trial, Erin L. Abner, Brandon C. Dennis, Melissa J. Mathews, Marta S. Mendiondo, Allison Caban-Holt, Richard J. Kryscio, Frederick A. Schmitt, John J. Crowley

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Practice effects are a known threat to reliability and validity in clinical trials. Few studies have investigated the potential influence of practice on repeated screening measures in longitudinal clinical trials with a focus on dementia prevention. The current study investigates whether practice effects exist on a screening measure commonly used in aging research, the Memory Impairment Screen (MIS).

METHODS: The PREADViSE trial is a clinical intervention study evaluating the efficacy of vitamin E and selenium for Alzheimer's disease prevention. Participants are screened annually for incident dementia with the MIS. Participants with baseline and three consecutive follow-ups who made less …

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Cannabis And Cognition: Short- And Long-Term Effects, Nadia Solowij, Nicole Pesa

Faculty of Health and Behavioural Sciences - Papers (Archive)

Twenty years ago cannabis was generally perceived to be a benign drug with few significant adverse effects. As outlined elsewhere in this book, evidence has since mounted in the scientific literature for a range of harms associated with the use of cannabis, including the development of dependence and health-related harms (see also Hall and Solowij, 1998; Hall and Degenhardt, 2009). As the overall theme of this book indicates, an association between cannabis use and the development of psychotic symptoms or overt psychosis has grown to be recognized as a significant potential harm, and investigating the mechanisms by which cannabis may …

Deficient Liver Biosynthesis Of Docosahexaenoic Acid Correlates With Cognitive Impairment In Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Nicole C. Berchtold, Vinh Q. Nguyen, Daniel L. Gillen, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P = 0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P = 0.005) and mid-frontal cortex (P = 0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's …

Cognitive And Psychiatric Predictors To Psychosis In Velocardiofacial Syndrome: A 3-Year Follow-Up Study, Kevin M. Antshel, Robert J. Shprintzen, Wanda Fremont, Anne Marie Higgins, Stephen V. Faraone, Wendy R. Kates

Communication Disorders Faculty Publications

Objective: To predict prodromal psychosis in adolescents with velocardiofacial syndrome (VCFS). Method: 70 youth with VCFS, 27 siblings of youth with VCFS and 25 community controls were followed from childhood (Mean age = 11.8 years) into mid-adolescence (mean age 15.0 years). Psychological tests measuring intelligence, academic achievement, learning/memory, attention and executive functioning as well as measures of parent and clinician ratings of child psychiatric functioning were completed at both time point. Results: Major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder diagnoses increased in the VCFS sample. With very low false positive rates, the best predictor of adolescent prodromal …

Arterial Pulse Wave Velocity And Cognition With Advancing Age, Merrill F. Elias, Michael A. Robbins, Marc M. Budge, Walter P. Abhayaratna, Gregory A. Dore, Penelope K. Elias

Maine-Syracuse Longitudinal Papers

We hypothesized that carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, interacts with age such that the magnitude of associations between PWV and cognitive performance are greater with increasing age and that this interaction is observed despite adjustments for demographic variables, mean arterial pressure, and cardiovascular risk factors. PWV was estimated using applanation tonometry in 409 dementia- and stroke-free participants of the Maine-Syracuse Longitudinal Study (24 to 92 years of age; 62.3% women). Using linear regression analyses in a cross-sectional design, associations between PWV and age and the interaction of PWV and age were examined in relation to …

Serum Cholesterol And Cognitive Performance In The Framingham Heart Study, Penelope K. Elias, Merrill F. Elias, Ralph B. D'Agostino, Lisa M. Sullivan, Philip A. Wolf

Maine-Syracuse Longitudinal Papers

Objective: The objective of this study was to examine the relationship between total cholesterol (TC) and cognitive performance within the context of the Framingham Heart Study, a large, community-based, prospective investigation of cardiovascular risk factors. Methods: Participants were 789 men and 1105 women from the Framingham Heart Study original cohort who were free of dementia and stroke and who received biennial TC determinations over a 16- to 18-year surveillance period. Cognitive tests were administered 4 to 6 years subsequent to the surveillance period and consisted of measures of learning, memory, attention/ concentration, abstract reasoning, concept formation, and organizational abilities. Statistical …