Medicine and Health Sciences Commons^™

Cognitive And Neuroscientific Perspectives Of Healthy Ageing, Jon B. Prince, Helen L. Davis, Jane Tan, Katrina Muller-Townsend, Shaun Markovic, David M. G. Lewis, Brianne Hastie, Matthew B. Thompson, Peter D. Drummond, Hakuei Fujiyama, Hamid R. Sohrabi

Research outputs 2022 to 2026

With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021–2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, …

Colonial Drivers And Cultural Protectors Of Brain Health Among Indigenous Peoples Internationally, Rita Henderson, Joyla A Furlano, Shayla Scott Claringbold, Ashley Cornect-Benoit, Anh Ly, Jennifer Walker, Lisa Zaretsky, Pamela Roach

Journal Articles

Despite relatively higher rates of dementia among Indigenous populations internationally, research into drivers of disparities in brain health and cognitive function has tended to focus on modifiable risk factors over cultural understandings and contextual determinants. By seeking to characterize social and cultural factors that shape brain health and cognition in Indigenous populations, this mini scoping review expands prevailing schools of thought to include Indigenous knowledge systems. This reveals important gaps in culturally aligned care. It also reclaims horizons for research important to Indigenous Peoples that have garnered diminished attention in biomedical approaches. Twenty-three sources were included for data extraction. This …

Assessment Of Deficits In Specific Cognitive Domains In Older Adults Living With Hiv., Andrea Reyes-Vega, Harideep Samanapally, Rishikesh Rijal, Stephen P. Furmanek, Christopher B. Shields, Brandon C. Dennis, Smita Ghare, Shirish Barve

Faculty Scholarship

A significant proportion of people living with HIV (PLWH) have cognitive impairment. Moreover, approximately 70% of PLWH in the United States will be ≥50 years old by 2030, raising concerns of a higher incidence of dementia as they age. Accordingly, there is a clinical need to monitor their cognitive status. The aim of this study was to delineate specific cognition areas impacted in OALWH with a clinical diagnosis of neurocognitive impairment. We used a comprehensive set of tests (paper and NIH Toolbox Cognition Battery), to assess different cognitive domains in a total of 25 OALWH ≥ 50 years. 64% were …

Longitudinal Associations Between Cognitive Functioning And Depressive Symptoms Among Couples In The Mexican Health And Aging Study, Joan K Monin, Gail Mcavay, Katie Newkirk, Rafael Samper-Ternent

Journal Articles

OBJECTIVE: To examine the bidirectional associations between older adult spouses' cognitive functioning and depressive symptoms over time and replicate previous findings from the United States (US) in Mexico.

DESIGN: Longitudinal, dyadic path analysis with the actor-partner interdependence model.

SETTING: Data were from the three most recent interview waves (2012, 2015, and 2018) of the Mexican Health and Aging Study (MHAS), a longitudinal national study of adults aged 50+ years in Mexico.

PARTICIPANTS: Husbands and wives from 905 community-dwelling married couples (N = 1,810).

MEASUREMENTS: The MHAS cognitive battery measured cognitive function. Depressive symptoms were assessed using a modified nine-item Center …

Plasma Metabolites Associated With Cognitive Function Across Race/Ethnicities Affirming The Importance Of Healthy Nutrition, Einat Granot-Hershkovitz, Shan He, Jan Bressler, Bing Yu, Wassim Tarraf, Casey M Rebholz, Jianwen Cai, Queenie Chan, Tanya P Garcia, Thomas Mosley, Bruce S Kristal, Charles Decarli, Myriam Fornage, Guo-Chong Chen, Qibin Qi, Robert Kaplan, Hector M González, Tamar Sofer

Journal Articles

INTRODUCTION: We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations.

METHODS: We tested metabolite-cognitive function associations in U.S.A. Hispanic/Latino adults (n = 2222) from the Community Health Study/ Study of Latinos (HCHS/SOL) and in European (n = 1365) and African (n = 478) Americans from the Atherosclerosis Risk In Communities (ARIC) Study. We applied Mendelian Randomization (MR) analyses to assess causal associations between the metabolites and cognitive function and between Mediterranean diet and cognitive function.

RESULTS: Six metabolites were consistently associated …

"I Just Want To Be Me, Authentically": Identity Shifting Among Racially And Ethnically Diverse Young Adults, Aerika Brittian Loyd, Dulce Wilkinson Westberg, Lenisha Williams, Marisha Humphries, Alan Meca, Julie Carmen Rodil

Psychology Faculty Publications

Identity shifting represents a common but complex social, behavioral, and cognitive phenomenon. However, some forms of identity shifting originate in response to structural, institutional, and interpersonal marginalization enacted on lower status groups, such as people of color in the United States. The current study investigated ways young adults from diverse ethnic/racial groups discussed shifting to fit in with White Americans (a dominant group) in the United States and their own ethnic/racial group (a minoritized group) and elucidated self-reported motivations for shifting. Participants consisted of 764 young adults (ages = 18–23) recruited from two large public universities in the Southeast and …

Home E-Cigarette Rules And Youth's Vulnerability To Initiate And Sustain E-Cigarette Use, Anne Buu, Joon Kyung Nam, Meng Yang, Wei-Chung Su, Hsien-Chang Lin

Journal Articles

Existing studies of the impact of home rules on youth's vulnerability to e-cigarette use were based on cross-sectional data, youth or parent reports alone, as well as youth's perceptions and susceptibility. This study capitalizes on the restricted-use data of the Population Assessment of Tobacco and Health (PATH) Study to examine the longitudinal association between home rules for e-cigarette use and youth's vulnerability including initiation of use and regular use two years later. Secondary analysis was conducted on 1203 parent-youth pairs who participated in both Wave 4 (2016-2018) and Wave 5 (2018-2019) assessment of the PATH Study and while the youth …

Early Life Exposure To Unpredictable Parental Sensory Signals Shapes Cognitive Development Across Three Species, Elyssia Poggi Davis, Kari Mccormack, Hina Arora, Desiree Sharpe, Annabel K. Short, Jocelyne Bachevalier, Laura M. Glynn, Curt A. Sandman, Hal S. Stern, Mar Sanchez, Tallie Z. Baram

Psychology Faculty Articles and Research

Exposure to early life adversity has long term consequences on cognitive function. Most research has focused on understanding components of early life adversities that contribute to later risk, including poverty, trauma, maltreatment, and neglect. Whereas these factors, in the aggregate, explain a significant proportion of emotional and cognitive problems, there are serious gaps in our ability to identify potential mechanisms by which early life adversities might promote vulnerability or resilience. Here we discuss early life exposure to unpredictable signals from the caretaker as an understudied type of adversity that is amenable to prevention and intervention. We employ a translational approach …

Occupational Depression In A Spanish-Speaking Sample: Associations With Cognitive Performance And Work-Life Characteristics, Bianchi Renzo, Guadalupe Manzano García, Maria Pilar Montanes, Emily A. Schonfeld, Irvin Sam Schonfeld

Publications and Research

This 386-participant study investigated the structural and psychometric properties of the Spanish version of the Occupational Depression Inventory (ODI). Exploratory structural equation modeling bifactor analysis revealed that the ODI meets the requirements for essential unidimensionality. Measurement invariance held across our sample and the English- and French-speaking samples used in the ODI’s initial validation study. Mokken scale analysis indicated that (a) the scalability of the instrument was strong, (b) no violations of monotonicity or local independence were present, and (c) invariant item ordering was sufficiently accurate. The ODI’s reliability was optimal. The ODI exhibited both convergent validity and discriminant validity vis-à-vis …

Eye Movement And Pupil Measures: A Review, Bhanuka Mahanama, Yasith Jayawardana, Sundararaman Rengarajan, Gavindya Jayawardena, Leanne Chukoskie, Joseph Snider, Sampath Jayarathna

Computer Science Faculty Publications

Our subjective visual experiences involve complex interaction between our eyes, our brain, and the surrounding world. It gives us the sense of sight, color, stereopsis, distance, pattern recognition, motor coordination, and more. The increasing ubiquity of gaze-aware technology brings with it the ability to track gaze and pupil measures with varying degrees of fidelity. With this in mind, a review that considers the various gaze measures becomes increasingly relevant, especially considering our ability to make sense of these signals given different spatio-temporal sampling capacities. In this paper, we selectively review prior work on eye movements and pupil measures. We first …

Parent Reports Of Executive Functions In Students With Learning Disability, Jane Roitsch, Annemarie L. Horn, Lisa Morin

Communication Disorders & Special Education Faculty Publications

This study examines the results of the Behavior Rating Inventory of Executive Function (BRIEF-2) (Gioia et al., 2015) reported by parents of children with Specific Learning Disability (LD) and/or other comorbid disabilities. LD is most notably associated with comorbid attention deficit hyperactivity disorder (ADHD) (Alloway & Stein, 2014; Westby &Watson, 2004; Willcutt et al., 2013). A total of 43 parents completed the BRIEF-2 rating scale. Findings suggest children with LD and ADHD display greater challenges with inhibition, working memory, planning, along with greater challenges in organization and metacognition. Parents of children with LD reported their children have greater levels of …

The Cerebellum's Relationship To Language Function Following Perinatal Stroke, Carolina Alexis Vias

FIU Electronic Theses and Dissertations

While recent studies have demonstrated the association between the cerebellum and higher-order cognitive functioning, it is still unclear how volumetric differences of specific regions of interests within the cerebellum across typical and atypical development are related to language function. We have done so by measuring the volume of cerebellar subregions of healthy controls, and compared the volume to behavioral measures of language function. We then followed with an analysis of the cerebellum’s relationship to language function following perinatal stroke, which provides us with a greater knowledge of the impact of a cortical injury on cerebellar development and the cognitive outcomes …

The Influence Of Mental Fatigue On Sessional Ratings Of Perceived Exertion In Elite Open And Closed Skill Sports Athletes, Joseph O. C. Coyne, Aaron J. Coutts, Robert U. Newton, G. Gregory Haff

Research outputs 2014 to 2021

ABSTRACT: Coyne, JOC, Coutts, AJ, Newton, RU, and Haff, GG. The influence of mental fatigue on sessional ratings of perceived exertion in elite open and closed skill sports athletes. J Strength Cond Res 35(4): 963-969, 2021-The main purpose of this investigation was to examine influence of mental fatigue on sessional ratings of perceived exertion (sRPE) over a training week in elite athletes in open skill (OS, i.e., more unpredictable and externally paced sports) and closed skill (CS, i.e., more predictable and internally paced) sports. Visual analogue scales for mental fatigue, sRPE (CR-10 scale), and training duration were collected from an …

L-Theanine Prevents Long-Term Affective And Cognitive Side Effects Of Adolescent Δ-9-Tetrahydrocannabinol Exposure And Blocks Associated Molecular And Neuronal Abnormalities In The Mesocorticolimbic Circuitry, Marta De Felice, Justine Renard, Roger Hudson, Hanna J. Szkudlarek, Brian J. Pereira, Susanne Schmid, Walter J. Rushlow, Steven R. Laviolette

Brain and Mind Institute Researchers' Publications

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. L-Theanine is an amino acid analog of L-glutamate and L-glutamine derived from various plant sources, including green tea leaves. L-Theanine has previously been …

New Frontiers In Translational Research: Touchscreens, Open Science, And The Mouse Translational Research Accelerator Platform, Jacqueline A. Sullivan, Julie R. Dumont, Sara Memar, Miguel Skirzewski, Jinxia Wan, Maryam H. Mofrad, Hassam Zafar Ansari, Yulong Li, Lyle Muller, Vania F. Prado, Marco A.M. Prado, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2020 International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd Many neurodegenerative and neuropsychiatric diseases and other brain disorders are accompanied by impairments in high-level cognitive functions including memory, attention, motivation, and decision-making. Despite several decades of extensive research, neuroscience is little closer to discovering new treatments. Key impediments include the absence of validated and robust cognitive assessment tools for facilitating translation from animal models to humans. In this review, we describe a state-of-the-art platform poised to overcome these impediments and improve the success of translational research, the Mouse Translational Research Accelerator Platform (MouseTRAP), which is …

Occupational Depression, Cognitive Performance, And Task Appreciation: A Study Based On Raven’S Advanced Progressive Matrices, Renzo Bianchi, Irvin Sam Schonfeld

Publications and Research

The Occupational Depression Inventory (ODI) was recently developed to assess depressive symptoms that individuals specifically attribute to their work. Research on the criterion validity of the instrument is still in its infancy. In this study, we examined whether the ODI predicted performance on, and appreciation of, a cognitively challenging test. In light of the link established between clinical depression and neuropsychological impairment, and considering that individuals with depressive symptoms are more likely to feel helpless under challenging circumstances, we hypothesized that occupational depression would be associated with poorer cognitive performance and a darkened appreciation of the task undertaken. We relied …

Correlation Between Cognition And Balance Among Middle-Aged And Older Adults Observed Through A Tai Chi Intervention Program, Tao Xiao, Lin Yang, Lee Smith, Paul D. Loprinzi, Nicola Veronese, Jie Yao, Zonghao Zhang, Jane Jie Yu

Faculty and Student Publications

© Copyright © 2020 Xiao, Yang, Smith, Loprinzi, Veronese, Yao, Zhang and Yu. Background: Age-associated decline in cognition and balance may cause severe ability loss for daily living activities among middle-aged and older adults. The relationship between cognition and balance in this aging population remains to be explored. Objective: The present study Is exploratory in nature and aimed to examine the relationship between balance (both static and dynamic components) and global cognitive function among middle-aged and older adults through Tai Chi (TC) practice as a research avenue. Methods: A short-term (12 weeks) intervention of TC was conducted among middle-aged and …

Hypothesized Mechanisms Through Which Exercise May Attenuate Memory Interference, Lindsay K. Crawford, Hong Li, Liye Zou, Gao Xia Wei, Paul D. Loprinzi

Faculty and Student Publications

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In this paper we introduce a mechanistic model through which exercise may enhance episodic memory, specifically via attenuating proactive and retroactive memory interference. We discuss the various types of memory, different stages of memory function, review the mechanisms behind forgetting, and the mechanistic role of exercise in facilitating pattern separation (to attenuate memory interference).

The Project Talent Twin And Sibling Study: Zygosity And New Data Collection, Carol A. Prescott, Ellen E. Walters, Thalida Em Arpawong, Catalina Zavala, Tara L. Gruenewald, Margaret Gatz

Psychology Faculty Articles and Research

The Project Talent Twin and Sibling (PTTS) study includes 4481 multiples and their 522 nontwin siblings from 2233 families. The sample was drawn from Project Talent, a U.S. national longitudinal study of 377,000 individuals born 1942–1946, first assessed in 1960 and representative of U.S. students in secondary school (Grades 9–12). In addition to the twins and triplets, the 1960 dataset includes 84,000 siblings from 40,000 other families. This design is both genetically informative and unique in facilitating separation of the ‘common’ environment into three sources of variation: shared by all siblings within a family, specific to twin-pairs, and associated with …

Evaluation Of A Cognitive Affective Model Of Physical Activity Behavior, Paul D. Loprinzi, Sara Pazirei, Gina Robinson, Briahna Dickerson, Meghan Edwards, Ryan E. Rhodes

Faculty and Student Publications

© 2020 The Author(s). Background: To empirically evaluate a cognitive affective model of physical activity. This bidirectional, cyclical model hypotheses that executive control processes directly influence habitual engagement in exercise and also directly subserve the exercise-induced affective response to acute exercise associated with future physical activity. Methods: The present study employed a one-week prospective, multi-site design. Participant recruitment and data collection occurred at two separate University sites (one in the United States and the other in Canada). Participants completed a bout of treadmill exercise, with affect and arousal assessed before, during and after the bout of exercise. Subjective and objective …

Acute Exercise On Memory Function: Open Vs. Closed Skilled Exercise, Justin Cantrelle, Grace Burnett, Paul D. Loprinzi

Faculty and Student Publications

© 2020 The Author(s). Background: Previous studies suggest that acute exercise may improve memory function. Few studies, however, have investigated the differential effect of the acute exercise movement patterns on memory. Such an effect is plausible, as research demonstrates that open-skilled exercise (e.g., racquetball) may have a greater effect on memory-related neurotrophins (e.g., brain-derived neurotrophic factors) when compared to closed-skilled exercise (e.g. treadmill exercise). A key distinction between open- and closed-skilled exercise is that open-skilled exercises are those that require an individual to react in a dynamic way to a changing, unpredictable environment. Our aim in this study was to …

Across Continents And Demographics, Unpredictable Maternal Signals Are Associated With Children's Cognitive Function, Elyssia Poggi Davis, Riikka Korja, Linnea Karlsson, Laura Glynn, Curt A. Sandman, Brian Vegetabile, Eeva-Leena Kataja, Saara Nolvi, Eija Sinervä, Juho Pelto, Hasse Karlsson, Hal S. Stern, Tallie Z. Baram

Psychology Faculty Articles and Research

Background

Early life experiences have persisting influence on brain function throughout life. Maternal signals constitute a primary source of early life experiences, and their quantity and quality during sensitive developmental periods exert enduring effects on cognitive function and emotional and social behaviors. Here we examined if, in addition to established qualitative dimensions of maternal behavior during her interactions with her infant and child, patterns of maternal signals may contribute to the maturation of children's executive functions. We focused primarily on effortful control, a potent predictor of mental health outcomes later in life.

Methods

In two independent prospective cohorts in Turku, …

Acute Exercise And Mindfulness Meditation On Learning And Memory: Randomized Controlled Intervention, Malina Austin, Paul D. Loprinzi

Faculty and Student Publications

© 2019 The Author(s). Background: The purpose of this experiment was to evaluate the potential combined effects of acute exercise and mindfulness mediation on episodic memory. Methods: All data collection occurred in the authors’ laboratory (January to May of 2019). In this three-arm, within-subject design, participants (N=20; Mage=21.6 years) completed three counterbalanced laboratory visits, including Exercise Only, Exercise + Meditation and Control. Learning and memory were assessed from a word-list task. A one-factor repeated-measures ANOVA was computed for two memory outcomes, including the learning outcome (average performance across the 6 trials) and the long-term memory recall (10-minute delay). Results: The …

Cognitive Dysfunction In Naturally Occurring Canine Idiopathic Epilepsy, Rowena M.A. Packer, Paul D. Mcgreevy, Hannah Salvin, Michael Valenzuela, Chloe M. Chaplin, Holger A. Volk

Neurology Collection

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in …

Interpretation Bias Toward Ambiguous Information In Burnout And Depression, Renzo Bianchi, Eric Laurent, Irvin Sam Schonfeld, Jay Verkuilen, Chantal Berna

Publications and Research

Burnout has been defined as a job-related syndrome combining pervasive fatigue and loss of motivation. In recent years, evidence has mounted that burnout may reflect a depressive condition. In this study, we expanded on past investigations of burnout-depression overlap by focusing on interpretation biases toward ambiguous information among the two entities. We conducted a web-based study involving 1056 participants (83% female; mean age: 42.87). Burnout symptoms were assessed with the Shirom-Melamed Burnout Measure and depressive symptoms with the PHQ-9. The Ambiguous Scenarios Test (AST), a measure of interpretation bias validated among dysphoric individuals, was the outcome of interest. The AST …

Relationships Among Apathy, Health-Related Quality Of Life, And Function In Huntington's Disease., Nora E Fritz, Nicholas R Boileau, Julie C Stout, Rebecca Ready, Joel S Perlmutter, Jane S Paulsen, Kimberly Quaid, Stacey Barton, Michael K Mccormack, Susan L Perlman, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Up to 90% of individuals with Huntington's disease (HD)-a progressive, inherited neurodegenerative disorder-experience apathy. Apathy is particularly debilitating because it is marked by a reduction in goal-directed behaviors, including self-care, social interactions, and mobility. The objective of this study was to examine relationships between variables of apathy, functional status, physical function, cognitive function, behavioral status/emotional function, and health-related quality of life. Clinician-rated measures of physical, cognitive, and behavioral function, including one clinician-rated item on apathy, and self-reported measures of physical function, health-related quality of life, and emotional, cognitive, and social function were collected in a single session from 487 persons …

Higher And Lower Order Factor Analyses Of The Temperament In Middle Childhood Questionnaire., Yuliya Kotelnikova, Thomas M Olino, Daniel N Klein, Sarah V M Mackrell, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

The Temperament in Middle Childhood Questionnaire (TMCQ) is a widely used parent-report measure of temperament. However, neither its lower nor higher order structures has been tested via a bottom-up, empirically based approach. We conducted higher and lower order exploratory factor analyses (EFAs) of the TMCQ in a large ( N = 654) sample of 9-year-olds. Item-level EFAs identified 92 items as suitable (i.e., with loadings ≥.40) for constructing lower order factors, only half of which resembled a TMCQ scale posited by the measure's authors. Higher order EFAs of the lower order factors showed that a three-factor structure (Impulsivity/Negative Affectivity, Negative …

Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in …

Online Neural Monitoring Of Statistical Learning., Laura J Batterink, Ken A Paller

Brain and Mind Institute Researchers' Publications

The extraction of patterns in the environment plays a critical role in many types of human learning, from motor skills to language acquisition. This process is known as statistical learning. Here we propose that statistical learning has two dissociable components: (1) perceptual binding of individual stimulus units into integrated composites and (2) storing those integrated representations for later use. Statistical learning is typically assessed using post-learning tasks, such that the two components are conflated. Our goal was to characterize the online perceptual component of statistical learning. Participants were exposed to a structured stream of repeating trisyllabic nonsense words and a …

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: …