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SCN2A-Related Disorders
- Alfred L. George, Jr., Megan Abbott, Kevin J. Bender, Andreas Brunklaus, Scott Demarest, Shawn Egan, Isabel Haviland, Jennifer A. Kearney, Leah Schust Myers, Heather E. Olson, Stephan J. Sanders, Christina SanInocencio, Joseph Symonds, Christopher H. Thompson
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- June 2024
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- 30 June 2024
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SCN2A encodes a voltage-gated sodium channel (designated NaV1.2) vital for generating neuronal action potentials. Pathogenic SCN2A variants are associated with a diverse array of neurodevelopmental disorders featuring neonatal or infantile onset epilepsy, developmental delay, autism, intellectual disability and movement disorders. SCN2A is a high confidence risk gene for autism spectrum disorder and a commonly discovered cause of neonatal onset epilepsy. This remarkable clinical heterogeneity is mirrored by extensive allelic heterogeneity and complex genotype-phenotype relationships partially explained by divergent functional consequences of pathogenic variants. Emerging therapeutic strategies targeted to specific patterns of NaV1.2 dysfunction offer hope to improving the lives of individuals affected by SCN2A-related disorders. This Element provides a review of the clinical features, genetic basis, pathophysiology, pharmacology and treatment of these genetic conditions authored by leading experts in the field and accompanied by perspectives shared by affected families. This title is also available as Open Access on Cambridge Core.
Chapter 12 - Preparing the Next Generation of Extension Professionals
- from Part III - Looking Ahead: Emerging Issues and Trends
- Edited by Maria Rosario T. de Guzman, University of Nebraska, Lincoln, Holly Hatton, University of Nebraska, Lincoln
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- Extension Education and the Social Sciences
- Published online:
- 28 March 2024
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- 04 April 2024, pp 246-266
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Summary
This chapter addresses the critical question of how the Cooperative Extension System prepares the next generation of Extension professionals who will support the well-being of tomorrow’s children, youth, and families. This chapter details the career landscape of Extension in five parts. Part 1 presents a synopsis of career development research highlighting how a person identifies and advances in a career as well as different Extension careers to demonstrate the multiple career pathways and roles in Extension organizations. Part 2 provides a discussion of competencies and skills needed for successful Extension professionals. Parts 3, 4, and 5 explore each of the primary mechanisms for preparing the next generation of Extension professionals, including formal instruction through college programs, career development activities (e.g., internships); and education that occurs on or after hiring (e.g., onboarding, continuing professional development). Information from this chapter can help guide those interested in pursuing Extension careers, as well as those in leadership positions who oversee hiring and retaining talent for Extension.
284 Co-Creation in Action: Design and Implementation of a Studio to Increase Inclusion in Research
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- Stacey M. Gomes, Sarah J. Beal, Joseph Kiesler, Carley L. Riley, Monica J. Mitchell
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 87
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OBJECTIVES/GOALS: The goal of theIntegrating Special Populations (ISP) Studiosis tointegrate communityvoice into research design and en hance diversity, equity, and inclusion in research, and disseminate findings in ways that improve health literacy and equity. METHODS/STUDY POPULATION: Based on the Vanderbilt Community Engagement Studio model, the ISP Studiowas designed through multiple phases, including Designand PilotStudioSessions. Stakeholders were diverse representatives of community and academic organizations serving special populations, as well asself-identified persons within special populations as defined by the NIH.Each phase of development and implementation of the Studio included an evaluation consisting of Likert scale and open-ended survey questions for process improvement and to integrate voices of the ISP community continuously. Demographic information and program outcomes were also collected via the evaluation survey. RESULTS/ANTICIPATED RESULTS: All Design Session (N=9) and Pilot Studio (N=10) participants indicated that the Design and Pilot were positive, relevant, bidirectionally useful, and fostered respect, trust, and inclusion. 100% of the panel strongly agreed the Studio met its goals and that the ISP Studios have potentialtobenefitspecial and under represented populations. Qualitative data and discussion on design will also be shared. Additi onaland relevant pointsincludepanelisttraining,compensation for community panelists, and ensuring accessibility. Evaluation outcomes from initial implementation of the ISP Studio will be discussed. DISCUSSION/SIGNIFICANCE: The ISP Studio is an innovative model that may increase engagement of special populations in the research process through co-creation and integration of lived experiences.It has the potential to improve research design, implementation, and impact.
Crystal Structure of Cronstedtite-2H2
- Charles A. Geiger, Diane L. Henry, S. W. Bailey, Joseph J. Maj
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- Clays and Clay Minerals / Volume 31 / Issue 2 / April 1983
- Published online by Cambridge University Press:
- 02 April 2024, pp. 97-108
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The crystal structure of a magnesian cronstedtite-2H2 from Pribram, Czechoslovakia, was refined in space group C1 to a residual of 5.4% with 1832 independent reflections. Tetrahedral ordering between Fe3+ and Si is judged to be complete on the basis of electron density maps, the first confirmation of such ordering in a layer silicate. Octahedral cations are disordered on the M sites. Mean T-O bond lengths do not confirm the tetrahedral ordering, perhaps due to tetrahedral distortion in order to relieve the extreme corrugation of the sheet that would arise from ordering of such different size cations.
In the initial stages of refinement the structure of the crystal under study could not be described adequately on the basis of a single 2H2 polytype. The structure contains two kinds of 2H2 domains that appear shifted by b/3 relative to one another due to a mistake in the interlayer stacking sequence. This mistake of zero shift (the normal 2H2 polytype consists of alternating —b/3 and +b/3 shifts) affects only the tetrahedral sheets. It creates adjacent enantiomorphic domains of 2H2 packets such that domains with small Si tetrahedra sit above larger Fe3+-rich tetrahedra and vice versa. This mechanism to relieve strain may indeed be the cause of the stacking mistakes. A third kind of domain contains regions in which the sense of tetrahedral rotation is reversed, giving rise to split basal oxygens on electron density maps. This multiple domain model best explains extra atomic positions observed on Fourier maps, lack of streaking of k ≠ 3n reflections, and possible nonintegral “satellitic” reflections observed on Weissenberg films.
Determinants of confrontation naming deficits on the Boston Naming Test associated with transactive response DNA-binding protein 43 pathology
- Carling G. Robinson, Austin W. Goodrich, Stephen D. Weigand, Nha Trang Thu Pham, Arenn F. Carlos, Marina Buciuc, Melissa E. Murray, Aivi T. Nguyen, R. Ross Reichard, David S. Knopman, Ronald C. Petersen, Dennis W. Dickson, Rene L. Utianski, Jennifer L. Whitwell, Keith A. Josephs, Mary M. Machulda
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- Journal:
- Journal of the International Neuropsychological Society , First View
- Published online by Cambridge University Press:
- 25 March 2024, pp. 1-9
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Objective:
To determine whether poorer performance on the Boston Naming Test (BNT) in individuals with transactive response DNA-binding protein 43 pathology (TDP-43+) is due to greater loss of word knowledge compared to retrieval-based deficits.
Methods:Retrospective clinical-pathologic study of 282 participants with Alzheimer’s disease neuropathologic changes (ADNC) and known TDP-43 status. We evaluated item-level performance on the 60-item BNT for first and last available assessment. We fit cross-sectional negative binomial count models that assessed total number of incorrect items, number correct of responses with phonemic cue (reflecting retrieval difficulties), and number of “I don’t know” (IDK) responses (suggestive of loss of word knowledge) at both assessments. Models included TDP-43 status and adjusted for sex, age, education, years from test to death, and ADNC severity. Models that evaluated the last assessment adjusted for number of prior BNT exposures.
Results:43% were TDP-43+. The TDP-43+ group had worse performance on BNT total score at first (p = .01) and last assessments (p = .01). At first assessment, TDP-43+ individuals had an estimated 29% (CI: 7%–56%) higher mean number of incorrect items after adjusting for covariates, and a 51% (CI: 15%–98%) higher number of IDK responses compared to TDP-43−. At last assessment, compared to TDP-43−, the TDP-43+ group on average missed 31% (CI: 6%–62%; p = .01) more items and had 33% more IDK responses (CI: 1% fewer to 78% more; p = .06).
Conclusions:An important component of poorer performance on the BNT in participants who are TDP-43+ is having loss of word knowledge versus retrieval difficulties.
Insights from 20 years of mammal population research in Indonesia
- Ardiantiono, Irene M.R. Pinondang, Desy S. Chandradewi, Gono Semiadi, Freddy Pattiselanno, Jatna Supriatna, Johny S. Tasirin, Nurul L. Winarni, Maria Voigt, Joseph W. Bull, Tatyana Humle, Nicolas J. Deere, Matthew J. Struebig
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- Oryx , First View
- Published online by Cambridge University Press:
- 22 March 2024, pp. 1-8
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Mammal populations are declining in biodiverse tropical regions. Global analyses have identified Indonesia as a hotspot of vertebrate decline, although relatively few data are available to substantiate these claims. We reviewed research articles published during 2000–2020 on 104 medium-sized to large terrestrial mammal species found in Indonesia to help inform conservation management and future research. We identified 308 peer-reviewed studies published in English or Bahasa Indonesia, with an increase in publication rate (articles published per year) over time. Studies of species distributions dominated the literature, followed by publications on abundance, species diversity and combinations of these topics. Most publications concerned single-species studies conducted at a single location and a single point in time. We identify four key issues that should be addressed by future research and conservation efforts: (1) disproportionate focus on a small number of species; (2) geographical bias towards west Indonesia (Sumatra, Kalimantan and Java–Bali), with few published studies from central (Sulawesi, Nusa Tenggara and Maluku) and east (Papua) Indonesia; (3) limitations to survey design, sampling effort and data analysis; and (4) lack of long-term wildlife population studies. We also note challenges local researchers face in publishing their studies in international journals because of language barriers and costs. Greater use of existing biodiversity data and continued capacity building for local researchers, particularly those in central and east Indonesia, are critical to effectively guide future wildlife monitoring and improve the conservation status of Indonesian mammals.
Neuropsychological correlates of early grief in bereaved older adults
- Brianna M. Hoffmann, Nutta-on P. Blair, Timothy L. McAuliffe, Gyujoon Hwang, Eric Larson, Stacy A. Claesges, Abigail Webber, Charles F. Reynolds III, Joseph S. Goveas
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- International Psychogeriatrics , First View
- Published online by Cambridge University Press:
- 11 March 2024, pp. 1-6
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Prolonged grief disorder (PGD) is associated with impairments in cognitive functioning, but the neuropsychological correlates of early grief in older adults are poorly understood. This preliminary study cross-sectionally examined neuropsychological functioning in bereaved adults with high and low grief symptoms and a non-bereaved comparison sample and further explored the relationship between multidomain cognitive measures and grief severity. A total of ninety-three nondemented older adults (high grief: n = 44; low grief: n = 49) within 12 months post-bereavement and non-bereaved comparison participants (n = 43) completed neuropsychological battery including global and multiple domain-specific cognitive functioning. Linear regression models were used to analyze differences in multidomain cognitive measures between the groups and specifically examine the associations between cognitive performance and grief severity in the bereaved, after covariate adjustment, including depressive symptoms. Bereaved older adults with higher grief symptoms performed worse than those with lower symptoms and non-bereaved participants on executive functioning and attention and processing speed measures. In the bereaved, poorer executive functioning, attention and processing speed correlated with higher grief severity. Attention/processing speed–grief severity correlation was seen in those with time since loss ≤ 6 months, but not > 6 months. Intense early grief is characterised by poorer executive functioning, attention, and processing speed, resembling findings in PGD. The putative role of poorer cognitive functioning during early grief on the transition to integrated grief or the development of PGD remains to be elucidated.
Virtual care during COVID-19: The perspectives of older adults and their healthcare providers in a cardiac rehabilitation setting
- Cecilia Flores-Sandoval, Shannon L. Sibbald, Bridget L. Ryan, Tracey L. Adams, Neville Suskin, Robert McKelvie, Jacobi Elliott, Joseph B. Orange
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- Canadian Journal on Aging / La Revue canadienne du vieillissement , First View
- Published online by Cambridge University Press:
- 23 February 2024, pp. 1-8
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The present study aimed to explore the perspectives of older adults and health providers on cardiac rehabilitation care provided virtually during COVID-19. A qualitative exploratory methodology was used. Semi-structured interviews were conducted with 15 older adults and 6 healthcare providers. Five themes emerged from the data: (1) Lack of emotional intimacy when receiving virtual care, (2) Inadequacy of virtual platforms, (3) Saving time with virtual care, (4) Virtual care facilitated accessibility, and (5) Loss of connections with patients and colleagues. Given that virtual care continues to be implemented, and in some instances touted as an optimal option for the delivery of cardiac rehabilitation, it is critical to address the needs of older adults living with cardiovascular disease and their healthcare providers. This is particularly crucial related to issues accessing and using technology, as well as older adults’ need to build trust and emotional connection with their providers.
Nomenclature for stacking in phyllosilicates: Report of the Association Internationale pour l’etude des argiles (AIPEA) nomenclature committee for 2008
- Stephen Guggenheim, John M. Adams, Faïza Bergaya, Maria F. Brigatti, Victor A. Drits, Milton L. L. Formoso, Emilio Galán, Toshihiro Kogure, Helge Stanjek, Joseph W. Stucki
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- Clays and Clay Minerals / Volume 57 / Issue 1 / February 2009
- Published online by Cambridge University Press:
- 01 January 2024, pp. 134-135
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Examining Structural and Related Spectral Change in Mars-relevant Phyllosilicates After Experimental Impacts Between 10–40 GPa
- Lonia R. Friedlander, Timothy D. Glotch, Brian L. Phillips, John S. Vaughn, Joseph R. Michalski
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- Journal:
- Clays and Clay Minerals / Volume 64 / Issue 3 / June 2016
- Published online by Cambridge University Press:
- 01 January 2024, pp. 189-209
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Accurate clay mineral identification is key to understanding past aqueous activity on Mars, but martian phyllosilicates are old (>3.5 Ga) and have been heavily bombarded by meteoroid impacts. Meteoroid impacts can alter clay mineral structures and spectral signatures, making accurate remote sensing identifications challenging. This paper uses nuclear magnetic resonance (NMR) spectroscopy to examine the short-range structural deformation induced in clay mineral samples of known composition by artificial impacts and calcination. Structural changes are then related to changes in the visible-near infrared (VNIR) and mid-infrared (MIR) spectra of these clay mineral samples. The susceptibility of phyllosilicates to structural deformation after experimental impacts varies by structure. Experimental results showed that trioctahedral, Mg(II)-rich saponite was structurally resilient up to peak pressures of 39.8 GPa and its unchanged post-impact spectra reflected this. Experimental data on kaolinite showed that this Al(III)-rich, dioctahedral phyllosilicate was susceptible to structural alteration at peak pressures ⩾ 25.1 GPa. This result is similar to previously reported experimental results on the Fe(III)-rich dioctahedral smectite nontronite, suggesting that dioctahedral phyllosilicates may be more susceptible to shock-induced structural deformation than trioctahedral phyllosilicates. The octahedral vacancies present in dioctahedral phyllosilicates may drive this increased susceptibility to deformation relative to trioctahedral phyllosilicates with fully occupied octahedral sheets. Thermal alteration accompanies shock in meteoroid impacts, but shock differs from thermal alteration. NMR spectroscopy showed that structural deformation in thermally altered phyllosilicates differs from that found in shocked phyllosilicates. Similar to shock, dioctahedral phyllosilicates are also more susceptible to thermal alteration. This differential susceptibility to impact-alteration may help explain generic smectite identifications from heavily bombarded terrains on Mars.
4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 408-409
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Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
6 Association Between American Football Play and Parkinson's Disease: Analysis of the Fox Insight Data Set
- Hannah Bruce, Yorghos Tripodis, Michael McClean, Monica Korell, Caroline M Tanner, Brittany Contreras, Joshua Gottesman, Leslie Kirsch, Yasir Karim, Brett Martin, Joseph Palmisano, Thor D Stein, Jesse Mez, Robert A Stern, Charles H Adler, Chris Nowinski, Ann C McKee, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 415-416
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Objective:
Parkinsonism and Parkinson's disease (PD) have been described as consequences of repetitive head impacts (RHI) from boxing, since 1928. Autopsy studies have shown that RHI from other contact sports can also increase risk for neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Lewy bodies. In vivo research on the relationship between American football play and PD is scarce, with small samples, and equivocal findings. This study leveraged the Fox Insight study to evaluate the association between American football and parkinsonism and/or PD Diagnosis and related clinical outcomes.
Participants and Methods:Fox Insight is an online study of people with and without PD who are 18+ years (>50,000 enrolled). Participants complete online questionnaires on motor function, cognitive function, and general health behaviors. Participants self-reported whether they "currently have a diagnosis of Parkinson's disease, or parkinsonism, by a physician or other health care professional." In November 2020, the Boston University Head Impact Exposure Assessment was launched in Fox Insight for large-scale data collection on exposure to RHI from contact sports and other sources. Data used in this abstract were obtained from the Fox Insight database https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp on 01/06/2022. The sample includes 2018 men who endorsed playing an organized sport. Because only 1.6% of football players were women, analyses are limited to men. Responses to questions regarding history of participation in organized football were examined. Other contact and/or non-contact sports served as the referent group. Outcomes included PD status (absence/presence of parkinsonism or PD) and Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) for assessment of cognitive symptoms. Binary logistic regression tested associations between history and years of football play with PD status, controlling for age, education, current heart disease or diabetes, and family history of PD. Linear regressions, controlling for these variables, were used for the PDAQ-15.
Results:Of the 2018 men (mean age=67.67, SD=9.84; 10, 0.5% Black), 788 (39%) played football (mean years of play=4.29, SD=2.88), including 122 (16.3%) who played youth football, 494 (66.0%) played high school, 128 (17.1%) played college football, and 5 (0.7%) played at the semi-professional or professional level. 1738 (86.1%) reported being diagnosed with parkinsonism/PD, and 707 of these were football players (40.7%). History of playing any level of football was associated with increased odds of having a reported parkinsonism or PD diagnosis (OR=1.52, 95% CI=1.14-2.03, p=0.004). The OR remained similar among those age <69 (sample median age) (OR=1.45, 95% CI=0.97-2.17, p=0.07) and 69+ (OR=1.45, 95% CI=0.95-2.22, p=0.09). Among the football players, there was not a significant association between years of play and PD status (OR=1.09, 95% CI=1.00-1.20, p=0.063). History of football play was not associated with PDAQ-15 scores (n=1980) (beta=-0.78, 95% CI=-1.59-0.03, p=0.059) among the entire sample.
Conclusions:Among 2018 men from a data set enriched for PD, playing organized football was associated with increased odds of having a reported parkinsonism/PD diagnosis. Next steps include examination of the contribution of traumatic brain injury and other sources of RHI (e.g., soccer, military service).
6 Improved verbal fluency following unilateral right hemisphere subthalamic nucleus deep brain stimulation for Parkinson’s disease: Is implant hemisphere a modifiable risk factor for cognitive decline?
- Victor A Del Bene, Roy C Martin, Sarah A Brinkerhoff, Joseph W Olson, Dario Marotta, Christopher L Gonzalez, Kelly A Mills, J Nicole Bentley, Barton L Guthrie, Harrison C Walker
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 112-113
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Objective:
Non-motor symptoms, such as mild cognitive impairment and dementia, are an overwhelming cause of disability in Parkinson’s disease (PD). While subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for motor symptoms, declines in verbal fluency after bilateral DBS surgery have been widely replicated. However, little is known about cognitive outcomes following unilateral surgeries.
Participants and Methods:We enrolled 31 PD patients who underwent unilateral STN-DBS in a randomized, cross-over, double-blind study (SUNDIAL Trial). Targets were chosen based on treatment of the most symptomatic side (n = 17 left hemisphere and 14 right hemisphere). All participants completed a neuropsychological battery (FAS/CFL, AVLT, DKEFS Color-Word Test) at baseline, then 2, 4, and 6 months post-surgery. Outcomes include raw scores for verbal fluency, immediate and delayed recall, and DKEFS Color-Word Inhibition trial (Trial 3) completion time. At 2, 4, and 6 months, the neurostimulation type (directional versus ring mode) was randomized for each participant. We compared baseline scores for all cognitive outcome measures using Welch’s two-sample t-tests and used linear mixed effects models to examine longitudinal effects of hemisphere and stimulation on cognition. This test battery was converted to a teleneuropsychology administration because of COVID-19 mid-study, and this was included as a covariate in all statistical models, along with years of education, baseline cognitive scores, and levodopa equivalent medication dose at each time point.
Results:At baseline, patients who underwent left hemisphere implants scored lower on verbal fluency than right implants (t(20.66) = -2.49, p = 0.02). There were not significant differences between hemispheres in immediate recall (p = 0.57), delayed recall (p = 0.22), or response inhibition (p = 0.51). Post-operatively, left STN DBS patients experienced significant declines in verbal fluency over the study period (p = 0.02), while patients with right-sided stimulation demonstrated improvements (p < .001). There was no main effect of stimulation parameters (directional versus ring) on verbal fluency, memory, or inhibition, but there was a three-way interaction between time, stimulation parameters, and hemisphere on inhibition, such that left STN DBS patients receiving ring stimulation completed the inhibition trial faster (p = 0.035). After surgery, right STN DBS patients displayed faster inhibition times than patients with left implants (p = 0.015).
Conclusions:Declines in verbal fluency after bilateral stimulation are the most commonly reported cognitive sequalae of DBS for movement disorders. Here we found group level declines in verbal fluency after unilateral left STN implants, but not right STN DBS up to 6 months after surgery. Patients with right hemisphere implants displayed improvements in verbal fluency. Compared to bilateral DBS, unilateral DBS surgery, particularly in the right hemisphere, is likely a modifiable risk factor for verbal fluency declines in patients with Parkinson’s disease.
4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 409-410
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Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
3 Harmonized Memory and Language Function in the Harmonized Cognitive Assessment Protocol (HCAP) Across the United States and Mexico
- Miguel Arce Rentería, Emily M Briceño, Diefei Chen, Joseph Saenz, Jet M. J. Vonk, Lindsay Kobayashi, Chris Gonzalez, Rich Jones, Rebeca Wong, Kenneth M Langa, David R Weir, Jennifer J Manly, Alden L Gross
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 87-88
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Objective:
Cross-national neuropsychological research is needed to understand the social, economic, and cultural factors associated with cognitive risk and resilience across global aging populations. Memory and language have been shown to be sensitive to age-related cognitive decline and pathological cognitive aging processes and may be more sensitive to subtle cognitive decline than measures of global cognitive function. Thus, we aimed to derive and validate harmonized cognitive domain scores for memory and language across population-based studies in the US and Mexico.
Participants and Methods:Data came from the Health and Retirement Study (HRS) Harmonized Cognitive Assessment Protocol (HCAP) and the Mexican Health and Aging Study (MHAS) Ancillary Study on Cognitive Aging (Mex-Cog). We used confirmatory factor analysis methodology to create statistically co-calibrated cognitive domains of memory and language. We performed differential item functioning (DIF) analysis to evaluate measurement differences across studies, using a cultural neuropsychological approach to identify comparable items across studies (i.e., cross-study anchors). We evaluated harmonized scores by examining their relationship to age and education in each study.
Results:We included 3347 participants from the HRS-HCAP study [Mage=76.6(7.5), 60% female] and 2042 participants from the Mex-Cog study [Mage=68.1(9.0), 59% female]. Education was classified according to the International Standard Classification of Education in the following categories (HRS-HCAP and Mex-Cog, respectively): none or early childhood education: (0.7%; 50.5%), primary education (4.1%; 22.3%), lower secondary education (7.1%; 15.7%), upper secondary education (41.1%; 3.0%), and any college (47.1%; 8.5%). DIF analyses revealed that 5 out of the 7 memory items and 1 out of the 12 language items demonstrated statistical evidence of measurement differences across studies, meaning that these items measured each underlying cognitive construct differently across studies. After adjusting for DIF by not allowing the items with DIF to be cross-study anchors, harmonized memory and language scores showed generally the expected associations with age and education in each study. Increasing age was associated with lower memory (r=-0.40 in HRS-HCAP; r=-0.44 in Mex-Cog) and language (r=-0.31 in HRS-HCAP and r=-0.67 in Mex-Cog) scores. Increasing years of education was associated with better memory and language scores, with mean scores ranging from z=-0.86 and z=-0.29 among those with a primary education or lower to z=0.33 and z=0.90 among those with any college, for HRS-HCAP and Mex-Cog, respectively.
Conclusions:A cultural neuropsychology approach to statistical harmonization facilitates the generation of harmonized measures of cognitive functioning in cross-national studies. Future work can utilize these harmonized cognitive scores to investigate determinants of late-life cognitive decline and dementia in the US and Mexico.
31 Sex Differences in Emotion Regulation and Emotional Awareness in Middle Aged and Older Adults
- Jack R. Kaufman, Megan Armstrong, Jeremy Maciarz, Nikhil Palekar, Joseph Kim, Vincent Koppelmans, Robert C. Welsh, Scott A. Langenecker, Sara L. Weisenbach
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 820-821
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Objective:
We measured sex differences in emotion regulation (ER) abilities – relying on exercise of cognitive reappraisal – during an image rating task in adults over 55 years of age with varying degrees of depression symptom severity. We also collected a self-report measure on participants' views of their own ER capacities. Previous research by this group has demonstrated the importance of emotion processing in the context of sex and aging in depression. We hypothesized that females would (1) score higher on the Cognitive Reappraisal Facet of the ERQ, (2) be more successful in utilizing cognitive reappraisal skills in response to negative stimuli; and (3) have self-report scores on the ERQ that more closely match their success at cognitive reappraisal than would males.
Participants and Methods:capacities. Previous research by this group has demonstrated the importance of emotion processing in the context of sex and aging in depression. We hypothesized that females would (1) score higher on the Cognitive Reappraisal Facet of the ERQ, (2) be more successful in utilizing cognitive reappraisal skills in response to negative stimuli; and (3) have self-report scores on the ERQ that more closely match their success at cognitive reappraisal than would males.
Results:Only the first of our three outcome measures was successfully predicted by the model including age, MADRS scores, and sex as predictors. Scores on the ERQ cognitive reappraisal facet with sex accounted for 11.3% of the variance (F=7.344, p=.009). Age and depression symptom severity did not reach significance. Performance on the ERT itself and the correlation between the two were not meaningfully modeled.
Conclusions:Women showed both better cognitive reappraisal abilities overall and more insight into the level of those abilities, findings that fall in line with most ER literature. However, we found that females were also more likely than males to be skewed in the positive or “overconfident” direction; to overestimate those same abilities. This information is useful for clinicians interpreting self-report information in the emotion regulation domain. These findings may not generalize to a more diverse (racially and socioeconomically) population and given the cognitive nature of the reappraisal strategy; these results may not extend to a less educated population. These data will be useful to inform the interpretation of fMRI images from this same experiment.
74 The Impact of Motoric Dysfunction on Neuropsychological Test Performance Within an Electrical Injury Sample
- Maximillian A Obolsky, Humza Khan, Zachary J Resch, Jessica L Paxton, Jason R Soble, Joseph W Fink, Neil H Pliskin
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 67-68
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Objective:
Victims of electrical injury (EI) often experience injuries to the peripheral nervous system and neuromuscular damage that may diminish motor function, such as flexibility/dexterity. These difficulties may continue after rehabilitation due to the reorganization of muscle afferent projections during peripheral nerve regeneration. Therefore, understanding how patients with a history of thermal burn injuries perform on motoric measures is necessary to explain the impact neuromuscular damage has on both motor and non-motor tests of cognition. However, no studies have examined the impact of motor functioning on cognition in patients who experienced thermal and electrical injuries compared to an electrical shock injury. This study explored the impact of motor dysfunction and psychiatric distress measured by depression severity on psychomotor speed and executive test performances among EI patients with and without thermal burn injuries.
Participants and Methods:This cross-sectional study consisted of EI patients undergoing an outpatient neuropsychological evaluation, including tests of motor dexterity (Grooved Pegboard [GP]), psychomotor speed (Wechsler Adult Intelligence Scale-IV Coding, Trail Making Test [TMT] Part A), and executive functioning (Stroop Color and Word Test [SCWT] Color-Word trial, TMT Part B). The sample was 83% male and 17% female, 88% White, 3% Black, 5% Hispanic, and 2% other race/ethnicity, with a mean age of 43.9 years (SD=11.36), mean education of 12.9 years (SD=2.05), and mean depression severity of 20.05 (SD=12.59) on the Beck Depression Inventory-II (BDI-II). Exclusion criteria were: 1) injury history of moderate-to-severe head trauma, 2) >2 performance validity test failures, and 3) any amputation of the upper extremity. Regression analyses included GP T-Scores for dominant hand and BDI-II total score as independent variables and neuropsychological normative test data as dependent variables.
Results:Among validly performing patients with EI (n=86), regression analyses revealed GP performance accounted for significant variance (R2 =.153-.169) on all neuropsychological measures. Among EI patients with burn injuries (n=50), regression analyses revealed GP performance accounted for significant variance (R2 =.197-.266) on all neuropsychological measures. Among EI patients without burn injuries (n=36), analyses revealed that neither GP performance nor BDI-II severity accounted for significant variance across the neurocognitive tests (R2=.056-.142). Furthermore, among EI patients with burn injuries and the total sample, regression analyses revealed depression severity negatively predicted GP performance (R2 =.099-.13), however, in patients without burn injuries, depression did not predict GP performance (R2 =.052).
Conclusions:Overall, results showed that GP performance is a significant predictor of neurocognitive performance on both motor and non-motor measures in EI patients with burn injuries. Therefore, among EI patients with burn injuries, GP performance may have potential utility as an early indicator of injury severity, considering that it predicts neuropsychological test performance on measures of psychomotor speed and executive functioning. Lastly, depression predicted GP performance within the burn injury sample illustrating that psychological distress may negatively impact motor functionality.
Promoting equity, inclusion, and efficiency: A team science approach to the development of authorship guidelines for a multi-disciplinary research team
- Hannah Lewis, Barbara Biesecker, Sandra Soo-Jin Lee, Katherine Anderson, Galen Joseph, Charisma L. Jenkins, Joanna E. Bulkley, Michael C. Leo, Katrina A. B. Goddard, Benjamin S. Wilfond
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 30 November 2023, e265
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Large research teams and consortia present challenges for authorship. The number of disciplines involved in the research can further complicate approaches to manuscript development and leadership. The CHARM team, representing a multi-disciplinary, multi-institutional genomics implementation study, participated in facilitated discussions inspired by team science methodologies. The discussions were centered on team members’ past experiences with authorship and perspectives on authorship in a large research team context. Team members identified challenges and opportunities that were used to create guidelines and administrative tools to support manuscript development. The guidelines were organized by the three values of equity, inclusion, and efficiency and included eight principles. A visual dashboard was created to allow all team members to see who was leading or involved in each paper. Additional tools to promote equity, inclusion, and efficiency included providing standardized project management for each manuscript and making “concept sheets” for each manuscript accessible to all team members. The process used in CHARM can be used by other large research teams and consortia to equitably distribute lead authorship opportunities, foster coauthor inclusion, and efficiently work with large authorship groups.
A systematic review of chemical weed management in peanut (Arachis hypogaea) in the United States: challenges and opportunities
- Olumide S. Daramola, Joseph E. Iboyi, Gregory E. MacDonald, Ramdas G. Kanissery, Barry L. Tillman, Hardeep Singh, Pratap Devkota
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- Journal:
- Weed Science / Volume 72 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 24 November 2023, pp. 5-29
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Herbicides are the primary tool for controlling weeds in peanut (Arachis hypogaea L.) and are crucial to sustainable peanut production in the United States. The literature on chemical weed management in peanut in the past 53 yr (1970 to 2022) in the United States was systematically reviewed to highlight the strengths and weaknesses of different herbicides and identify current research gaps in chemical weed management. Residual weed control in peanut is achieved mainly with dimethenamid-P, ethalfluralin, pendimethalin, and S-metolachlor. More recently, the use of the protoporphyrinogen oxidase inhibitor flumioxazin and acetolactate synthase inhibitors, such as diclosulam, for residual weed control in peanut has increased considerably. Postemergence broadleaf weed control in peanut is achieved mainly with acifluorfen, bentazon, diclosulam, imazapic, lactofen, paraquat, and 2,4-DB, while the graminicides clethodim and sethoxydim are the major postemergence grass weed control herbicides in peanut. Although several herbicides are available for weed control in peanut, no single herbicide can provide season-long weed control due to limited application timing, lack of extended residual activity, variability in weed control spectrum, and rotational restrictions. Therefore, effective weed management in peanut often requires herbicide mixtures and/or sequential application of preplant-incorporated, preemergence, and/or postemergence herbicides. However, the available literature showed a substantive range in herbicide efficacy due to variations in environmental conditions and flushes of weed germination across years and locations. Despite the relatively high efficacy of herbicides, the selection of herbicide-resistant weeds is another area of increasing concern. Future research should focus on developing new strategies for preventing or delaying the development of resistance and improving herbicide efficacy within the context of climate change and emerging constraints such as water shortages, rising temperatures, and increasing CO2 concentration.