Medicine and Health Sciences Commons^™

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 …

Low Vision Depression Prevention Trial In Age-Related Macular Degeneration: A Randomized Clinical Trial., Barry W. Rovner, Robin J Casten, Mark T Hegel, Robert W Massof, Benjamin E Leiby, Allen C Ho, William S Tasman

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD).

DESIGN: Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months.

PARTICIPANTS: Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188).

INTERVENTIONS: Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment …

Characterizing Spoken Discourse In Individuals With Parkinson Disease Without Dementia, Angela C. Roberts

Electronic Thesis and Dissertation Repository

Background: The effects of disease (PD) on cognition, word retrieval, syntax, and speech/voice processes may interact to manifest uniquely in spoken language tasks. A handful of studies have explored spoken discourse production in PD and, while not ubiquitously, have reported a number of impairments including: reduced words per minute, reduced grammatical complexity, reduced informativeness, and increased verbal disruption. Methodological differences have impeded cross-study comparisons. As such, the profile of spoken language impairments in PD remains ambiguous.

Method: A cross-genre, multi-level discourse analysis, prospective, cross-sectional between groups study design was conducted with 19 PD participants (M_age = 70.74, M …

Motoric Cognitive Risk Syndrome: Multicountry Prevalence And Dementia Risk, Joe Verghese, Cedric Annweiler, Emmeline Ayers, Nir Barzilai, Olivier Beauchet, David A Bennett, Stephanie A Bridenbaugh, Aron S Buchman, Michele L Callisaya, Richard Camicioli, Benjamin Capistrant, Somnath Chatterji, Anne-Marie De Cock, Luigi Ferrucci, Nir Giladi, Jack M Guralnik, Jeffrey M Hausdorff, Roee Holtzer, Ki Woong Kim, Paul Kowal, Reto W Kressig, Jae-Young Lim, Susan Lord, Kenichi Meguro, Manuel Montero-Odasso, Susan W. Hunter, Mohan L Noone, Lynn Rochester, Velandai Srikanth, Cuiling Wang

Physical Therapy Publications

OBJECTIVES: Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk.

METHODS: Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

Implications Of Human Umbilical Cord Blood Cells: An Immunotherapeutic Strategy For Alzheimer's Disease, Donna Darlington

USF Tampa Graduate Theses and Dissertations

ABSTRACT

Alzheimer's disease (AD) is the most common progressive age related dementia and the fourth major cause of mortality in the elderly in the United States. AD is pathologically characterized by deposition of amyloid beta (Aβ) plaques in the brain parenchyma and neurofibrillary tangles (NFTs) within the neuronal soma. While pharmacological targets have been discovered, current strategies for the symptomatic or disease-modifying treatment of AD do not significantly slow or halt the underlying pathological progression of the disease. Consequently, more effective treatment is needed. One possibility for amelioration is using human umbilical cord blood cell (HUCBC) therapy. HUCBCs comprise a …

Skill Generalization Following Computer-Based Cognitive Retraining Among Individuals With Acquired Brain Injury, Jonathan William Alonso, Nisha E. Chadha, Jennifer Elizabeth Pulido

Dissertations, Masters Theses, Capstones, and Culminating Projects

Individuals with acquired brain injury (ABI) often experience cognitive deficits. This creates many challenges in learning or relearning skills and generalizing skills among different contexts and task demands. Computer-Based Cognitive Retraining (CBCR) is a common intervention utilized by occupational therapists to help remediate cognitive deficits in individuals with ABI. Although research has shown that CBCR programs are effective at improving cognitive domains, there is limited evidence to support generalization of these skills to functional daily living tasks. Therefore, the primary purpose of this study was to assess the occurrence of generalizing gained skills in overall cognition, attention, and memory from …

Effects Of Cognitive Status On Life Participation Of Cancer Survivors, Mary F. Baxter, Theresa Smith, Jennifer Wahowski

The Open Journal of Occupational Therapy

The purposes of this study were to identify the cognitive status of cancer survivors, determine the effect of cognitive status on function and participation in daily activities, and explore how cancer survivors perceive changes in their cognition. The study used a quantitative nonexperimental cross-sectional design. The participants included 35 cancer survivors from two different sites. Instruments included the Montreal Cognitive Assessment (MoCA) and the Reintegration to Normal Index-Postal Version (RNLI-P) in the measurement of cognitive impairment and functional performance respectively. Data were also collected with a supplemental questionnaire to explore participants’ perspectives on their cognitive difficulties and current function. The …

Baseline Experience With Modified Mini Mental State Exam: The Women's Health Initiative Memory Study (Whims), Stephen Rapp, Mark Espeland, Patricia Hogan, Beverly Jones, Elizabeth Dugan

Elizabeth Dugan

The Modified Mini Mental State Exam (3MS) is widely used for screening global cognitive functioning, however little is known about its performance in clinical trials. We report the distribution of 3MS scores among women enrolled in the Women's Health Initiative Memory Study (WHIMS) and describe differences in these scores associated with age, education, and ethnicity. The 3MS exams were administered to 7,480 women aged 65-80 who had volunteered for and were eligible for a clinical trial on postmenopausal hormone therapy. General linear models were used to describe demographic differences among scores. Factor analysis was used to characterize the correlational structure …

Aged Rats Are Hypo-Responsive To Acute Restraint: Implications For Psychosocial Stress In Aging, Heather M. Buechel, Jelena Popovic, Kendra Staggs, Katie L. Anderson, Olivier Thibault, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift …

Biological Basis For Cerebral Dysfunction In Schizophrenia In Contrast With Alzheimer’S Disease, Rodrigo O. Kuljis, Luis V. Colom, Leonel E. Rojo

Health & Biomedical Sciences Faculty Publications and Presentations

Schizophrenia and Alzheimer’s disease are two disorders that, while conceptualized as pathophysiologically and clinically distinct, cause substantial cognitive and behavioral impairment worldwide, and target apparently similar – or nearby – circuitry in regions such as the temporal and frontal lobes.We review the salient differences and similarities from selected historical, nosological, and putative mechanistic viewpoints, as a means to help both clinicians and researchers gain a better insight into these intriguing disorders, for which over a century of research and decades of translational development was needed to begin yielding treatments that are objectively effective, but still very far from entirely satisfactory. …

Validating The Western Neuro Sensory Stimulation Profile For Patients With Severe Traumatic Brain Injury Who Are Slow-To-Recover, Anne Cusick, Natasha Lannin, Robyn Hanssen, Jeanine Allaous

Illawarra Health and Medical Research Institute

Background/aim The Western Neuro Sensory Stimulation Profile (WNSSP) is designed to measure disorders of consciousness in people with severe traumatic brain injury who are slow-to-recover. This study explores internal consistency reliability and concurrent validity of the WNSSP with function and two other consciousness measures. Method Retrospective chart audit of all severe traumatic brain injury patients admitted to a specialist neurological rehabilitation centre from January 2001 to December 2006 in a vegetative or minimally conscious state. Medical record of demographical, clinical and Glasgow Coma Scale (GCS) data were recorded. To be included in the study, patients needed admission and discharge WNSSP …

Fmri Response During Figural Memory Task Performance In College Drinkers [Pre-Print], Alecia Dager, Sharma Jamadar, Michael Stevens, Rivkah I. Rosen, Rachel Jiantonio-Kelly, Jason-Flor Sisante, Sarah Raskin, Howard Tennen, Carol S. Austad, Rebecca Wood, Carolyn Fallahi, Godfrey D. Pearlson

Faculty Scholarship

Rationale: 18-25-year-olds show the highest rates of alcohol use disorders (AUD) and heavy drinking, which may have critical neurocognitive implications. Regions subserving memory may be particularly susceptible to alcohol-related impairments.

Objective: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural correlates of visual encoding and recognition among heavy drinking college students. We predicted that heavy drinkers would show worse memory performance and increased frontal/parietal activation and decreased hippocampal response during encoding.

Methods: Participants were 23 heavy drinkers and 33 demographically matched light drinkers, ages 18-20, characterized using quantity/frequency of drinking and AUD diagnosis. Participants …

Anxiety Disorders And School-Based Treatments: Assessing School Pyschologists' Knowledge And Perceptions, Kelly A. Myhasuk

PCOM Psychology Dissertations

Anxiety disorders are common in children and youth. Despite high prevalence rates, most children with anxiety disorders do not receive treatment. In fact, for the few children who are receiving treatment, schools are the primary source of mental health care. When left untreated, children experience significant disruptions in their academic, social, emotional, and behavioral functioning. Therefore, it is important for those working in schools to recognize and treat children with anxiety disorders. The present study surveyed school psychologists (n = 178) to assess their knowledge about anxiety disorders and about empirically supported school-based treatments. Also, this study sought to investigate …

A Life Span Approach To The Relationship Between Cholesterol, Late Onset Alzheimer’S Disease, And Cognitive Functioning Among Older Adults, Brian Downer

Theses and Dissertations--Gerontology

There is evidence that cholesterol presents an important risk factor for Alzheimer’s disease (AD), but the direction of this relationship is modified by age. High cholesterol during midlife and low cholesterol during late life are both associated with an increased risk for AD. This dissertation research engaged a life span approach to study the relationship between cholesterol, AD and cognitive functioning among older adults. The purpose of this research was to determine if trajectories of cholesterol from midlife through late life differ according to AD status and if these trajectories are associated with cognitive functioning during old age.

This research …

Risk Factors For Cerebrovascular Disease Mortality Among The Elderly In Beijing: A Competing Risk Analysis, Zhe Tang, Tao Zhou, Yanxia Luo, Changchun Xie, Da Huo, Lixin Tao, Lei Pan, Fei Sun, Huiping Zhu, Xinghua Yang, Wei Wang, Aoshuang Yan, Xia Li, Xiuhua Guo

Research outputs 2014 to 2021

Objective: To examine the associations of combined lifestyle factors and physical conditions with cerebrovascular diseases (CBVD) mortality, after accounting for competing risk events, including death from cardiovascular diseases, cancers and other diseases. Methods: Data on 2010 subjects aged over 55 years were finally analyzed using competing risk models. All the subjects were interviewed by the Beijing Longitudinal Study of Aging (BLSA), in China, between 1 January 1992 and 30 August 2009. Results: Elderly females were at a lower risk of death from CBVD than elderly males (HR = 0.639, 95% CI = 0.457-0.895). Increasing age (HR = 1.543, 95% CI …

Factors That Contribute To Balance And Mobility Impairments In Individuals With Huntington's Disease, Travis Cruickshank, Alvaro Reyes, Luis Peñailillo, Jennifer Thompson, Mel Ziman

Research outputs 2014 to 2021

Mobility and balance problems are common and often debilitating features of Huntington's disease (HD). In this exploratory study we aimed to investigate the influence of disease severity, severity of motor deficits, lower limb muscle strength, cognition, executive function, lean muscle mass and reactivity on mobility and balance.Twenty-two individuals with HD were recruited from the North Metropolitan Area Mental Health Service, Perth, Australia. Pertinent demographic, genetic and disease progression information was recorded prior to testing. Balance was assessed using dynamic and static balance tasks. Mobility was assessed using self-paced and fast-paced mobility measures. Cognitive and executive measures were used to assess …

Impact Of Nutrition On Cognition And Its Association With Blood And Brain Alzheimer Disease Related Biomarkers, Samantha Gardener

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the most common form of senile dementia, currently affects over 35 million people worldwide. While there is no cure or effective treatment, early intervention programs hold considerable promise. Following particular dietary patterns represents one potential intervention strategy accessible to all.

Results from previous studies investigating the association of diet, cognition and biomarkers of AD are inconsistent: Positive results have been reported (1-7), whilst others have shown no associations. Prior to this thesis, no study has assessed the relationship of four dietary patterns to cognition, blood-based and neuroimaging biomarkers of AD in a large highly-characterised ageing cohort. Participants …

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 …