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Impulsivity profiles across five harmonized longitudinal childhood preventive interventions and associations with adult outcomes
- Natalie Goulter, Masoumeh Amin-Esmaeili, Ryoko Susukida, Joseph M. Kush, Jennifer Godwin, Katherine Masyn, Robert J. McMahon, J. Mark Eddy, Nicholas S. Ialongo, Patrick H. Tolan, Conduct Problems Prevention Research Group, Holly C. Wilcox, Rashelle J. Musci
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- Development and Psychopathology , First View
- Published online by Cambridge University Press:
- 24 April 2024, pp. 1-14
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This study aimed to parse between-person heterogeneity in growth of impulsivity across childhood and adolescence among participants enrolled in five childhood preventive intervention trials targeting conduct problems. In addition, we aimed to test profile membership in relation to adult psychopathologies. Measurement items representing impulsive behavior across grades 2, 4, 5, 7, 8, and 10, and aggression, substance use, suicidal ideation/attempts, and anxiety/depression in adulthood were integrated from the five trials (N = 4,975). We applied latent class growth analysis to this sample, as well as samples separated into nonintervention (n = 2,492) and intervention (n = 2,483) participants. Across all samples, profiles were characterized by high, moderate, low, and low-increasing impulsive levels. Regarding adult outcomes, in all samples, the high, moderate, and low profiles endorsed greater levels of aggression compared to the low-increasing profile. There were nuanced differences across samples and profiles on suicidal ideation/attempts and anxiety/depression. Across samples, there were no significant differences between profiles on substance use. Overall, our study helps to inform understanding of the developmental course and prognosis of impulsivity, as well as adding to collaborative efforts linking data across multiple studies to better inform understanding of developmental processes.
Virtual Issue: Race in the United States in Social Science History
- Joseph O. Jewell, Mary Jo Maynes, Robert C. Lieberman, Rebecca Jean Emigh
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- Social Science History , First View
- Published online by Cambridge University Press:
- 19 April 2024, pp. 1-8
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VaTEST III: Validation of eight potential super-earths from TESS data
- Priyashkumar Mistry, Aniket Prasad, Mousam Maity, Kamlesh Pathak, Sarvesh Gharat, Georgios Lekkas, Surendra Bhattarai, Dhruv Kumar, Jack J. Lissauer, Joseph D. Twicken, Abderahmane Soubkiou, Francisco J. Pozuelos, Jon Jenkins, Keith Horne, Steven Giacalone, Khalid Barkaoui, Mathilde Timmermans, Cristilyn N. Watkins, Ramotholo Sefako, Karen A. Collins, David R. Ciardi, Catherine A. Clark, Boris S. Safonov, Avi Shporer, Joshua E. Schlieder, Zouhair Benkhaldoun, Chris Stockdale, Carl Ziegler, Emily A. Gilbert, Jehin Emmanuël, Felipe Murgas, Ian J. M. Crossfield, Martin Paegert, Michael B. Lund, Norio Narita, Richard P. Schwarz, Robert F. Goeke, Sergio B. Fajardo-Acosta, Steve B. Howell, Thiam-Guan Tan, Thomas Barclay, Yugo Kawai
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- Publications of the Astronomical Society of Australia / Volume 41 / 2024
- Published online by Cambridge University Press:
- 11 April 2024, e030
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NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.
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.
Genetic and non-genetic predictors of risk for opioid dependence
- Peter J. Na, Joseph D. Deak, Henry R. Kranzler, Robert H. Pietrzak, Joel Gelernter
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- Psychological Medicine / Volume 54 / Issue 8 / June 2024
- Published online by Cambridge University Press:
- 06 February 2024, pp. 1779-1786
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Background
Elucidation of the interaction of biological and psychosocial/environmental factors on opioid dependence (OD) risk can inform our understanding of the etiology of OD. We examined the role of psychosocial/environmental factors in moderating polygenic risk for opioid use disorder (OUD).
MethodsData from 1958 European ancestry adults who participated in the Yale-Penn 3 study were analyzed. Polygenic risk scores (PRS) were based on a large-scale multi-trait analysis of genome-wide association studies (MTAG) of OUD.
ResultsA total of 420 (21.1%) individuals had a lifetime diagnosis of OD. OUD PRS were positively associated with OD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.21–1.66). Household income and education were the strongest correlates of OD. Among individuals with higher OUD PRS, those with higher education level had lower odds of OD (OR 0.92, 95% CI 0.85–0.98); and those with posttraumatic stress disorder (PTSD) were more likely to have OD relative to those without PTSD (OR 1.56, 95% CI 1.04–2.35).
ConclusionsResults suggest an interplay between genetics and psychosocial environment in contributing to OD risk. While PRS alone do not yet have useful clinical predictive utility, psychosocial factors may help enhance prediction. These findings could inform more targeted clinical and policy interventions to help address this public health crisis.
Empowering the Participant Voice (EPV): Design and implementation of collaborative infrastructure to collect research participant experience feedback at scale
- Rhonda G. Kost, Alex Cheng, Joseph Andrews, Ranee Chatterjee, Ann Dozier, Daniel Ford, Natalie Schlesinger, Carrie Dykes, Issis Kelly-Pumarol, Nan Kennedy, Cassie Lewis-Land, Sierra Lindo, Liz Martinez, Michael Musty, Jamie Roberts, Roger Vaughan, Lynne Wagenknecht, Scott Carey, Cameron Coffran, James Goodrich, Pavithra Panjala, Sameer Cheema, Adam Qureshi, Ellis Thomas, Lindsay O’Neill, Eva Bascompte-Moragas, Paul Harris
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 06 February 2024, e40
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Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
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.
3 Emotional Expression in Infants with Agenesis of the Corpus Callosum: The Role of Callosal Connectivity in Early Temperament
- Jasmin Turner, Lauren D Haisley, Lana Hantzch, Kelly Botteron, Stephen Dager, Annette M Estes, Lisa Flake, Heather C Hazlett, Robert T Schultz, Joseph Piven, Jed T Elison, Lynn K Paul
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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. 403-404
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Objective:
Accumulating evidence suggests that corpus callosum development is critically involved in the emergence of behavioral and cognitive skills during the first two years of life and that structural abnormalities of the corpus callosum are associated with a variety of neurodevelopmental disorders. Indeed by adulthood ∼30% of individuals with agenesis of the corpus callosum (ACC), a congenital condition resulting in a partial or fully absent corpus callosum, exhibit phenotypic features consistent with autism spectrum disorder (ASD). However, very little is known about developmental similarities and/or differences among infants with ACC and infants who develop ASD. This study describes temperament in infants with ACC during the first year of life in comparison with a neurotypical control group. Additionally, it examines the potential contribution of disrupted callosal connectivity to early expression of temperament in ASD through comparison to children with high familial likelihood of ASD.
Participants and Methods:Longitudinal ratings of positive and negative emotionality were acquired at 6 and 12 months on the Infant Behavior Questionnaire-Revised across four groups of infants: isolated complete and partial ACC (n=104), high familial likelihood of ASD who do and do not have a confirmed ASD diagnosis (HL+ n=81, HL- n=282), and low-likelihood controls (LL- n=152).
Results:Overall, the ACC group demonstrated blunted affect, with significantly lower positive and negative emotionality than LL controls at both timepoints. Specifically, the ACC group exhibited lower activity and approach dimensions of positive emotionality at both timepoints, with lower high-intensity pleasure at 6 months and lower vocal reactivity at 12 months. On negative emotionality subscales, the ACC group exhibited lower distress to limitations and sadness at both timepoints, as well as lower falling reactivity at 6 months. The ACC and HL groups did not differ significantly on positive emotionality at either timepoint. However, negative emotionality was lower in the ACC group than the HL- group at both timepoints and lower than the HL+ group at 12 months, with lower distress to limitations and sadness ratings than both HL groups at both timepoints.
Conclusions:These findings highlight the importance of interhemispheric connections in facilitating active engagement and pursuit of pleasurable activities during the first year of life, as well as expression of sadness and distress to limitations. Notably, similarities between infants with ACC and infants at elevated familial risk of ASD suggest that disrupted callosal connectivity may specifically contribute to reductions in positive emotionality.
4 Language Development in Infants and Toddlers (12 to 24 months) with Agenesis of the Corpus Callosum
- Ella Bohlman, Jasmin Turner, Lauren D Haisley, Lana Hantzch, Kelly N Botteron, Stephen Dager, Annette M Estes, Lisa Flake, Heather C Hazlett, Robert Schultz, Joseph Piven, Jed Elison, Lynn Paul
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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. 404-405
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Objective:
It is unclear how agenesis of the corpus callosum (ACC), a congenital brain malformation defined by complete or partial absence of the corpus callosum, impacts language development. fMRI studies of middle childhood suggest that the corpus callosum plays a role in the interhemispheric language network (Bartha-Doering et al., 2020), and that reduced interhemispheric functional connectivity is correlated with worse language abilities in children with ACC (Bartha-Doering et al., 2021). Additionally, accumulating evidence suggests structural abnormalities of the corpus callosum play a role in neurodevelopmental disorders. While children who go on to receive an autism spectrum disorder (ASD) diagnosis may show early signs of altered word and gesture acquisition (Iverson et al., 2018), the same is not known about ACC. This study examined language development during the second year of life in children with ACC in comparison to neurotypical control participants, as well as other children at elevated risk of ASD.
Participants and Methods:The MacArthur-Bates Communicative Development Inventories (MCDI): Words and Gestures scales were administered to parents of 74 children with isolated ACC at 12, 18 and 24 months of age. Children whose first language was not English and children who were bilingual were excluded. Comparison groups consisted of individuals with a low familial likelihood of ASD (LL- n=140) and individuals with high familial likelihood of ASD who do and do not have a confirmed ASD diagnosis (HL+ n=68, HL- n=256).
Results:Compared to LL controls, the ACC group produced fewer words at 18 and 24 months of age, and demonstrated fewer words understood at all three timepoints. Similarly, compared to the HL- group, the ACC group demonstrated fewer words produced and understood at 18 months of age, and fewer words produced at 24 months of age. The ACC and HL+ groups did not differ in words produced or words understood at any timepoint.
Conclusions:Overall, infants with ACC demonstrated delayed vocabulary expansion from 12 to 24 months of age. These findings illustrate the role of callosal connectivity in the development of language across the first 2 years of life, and highlight the need for support and interventions that target vocabulary production and comprehension.
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 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).
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 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.
59 Objectively-Measured Performance on Tests of Episodic Memory and Executive Function in Autopsy-Confirmed Chronic Traumatic Encephalopathy
- Madeline Uretsky, Evan Nair, Nicole Saltiel, Bobak Abdolmohammadi, Sydney Mosaheb, Julia Culhane, Brett Martin, Joseph Palmisano, Yorghos Tripodis, Robert Stern, Victor Alvarez, Bertrand Russell Huber, Thor Stein, Ann McKee, Jesse Mez, Michael 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. 264-265
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Objective:
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that can only be diagnosed at post-mortem. Revised criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES), include impairments in episodic memory and/or executive function as core clinical features. These criteria were informed by retrospective interviews with next-of-kin and the presence and rates of objective impairments in memory and executive functions in CTE are unknown. Here, we characterized antemortem neuropsychological test performance in episodic memory and executive functions among deceased contact sport athletes neuropathologically diagnosed with CTE.
Participants and Methods:The sample included 80 deceased male contact sport athletes from the UNITE brain bank who had autopsy-confirmed CTE (and no other neurodegenerative diseases). Published criteria were used for the autopsy diagnosis of CTE. Neuropsychological test reports (raw scores) were acquired through medical record requests. Raw scores were converted to z-scores using the same age, sex, and education-adjusted normative data. Tests of memory included long delay trials from the Rey Complex Figure, CVLT-II, HVLT-R, RBANS, and BVMT-R. Tests of executive functions included Trail Making Test-B (TMT-B), Controlled Oral Word Association Test, WAIS-III Picture Arrangement, and various WAIS-IV subtests. Not all brain donors had the same tests, and the sample sizes vary across tests, with 33 donors having tests from both domains. Twenty-eight had 1 test in memory and 3 had 2+. Eight had 1 test of executive function and 46 had 2+. A z-score of 1.5 standard deviations below the normative mean was impaired. Interpretation of test performance followed the American Academy of Clinical Neuropsychology guidelines (Guilmette et al., 2020). Bivariate correlations assessed cumulative p-tau burden (summary semiquantitative ratings of p-tau severity across 11 brain regions) and TMT-B (n=34) and CVLT-II (n=14), the most common tests available.
Results:Of the 80 (mean age= 59.9, SD=18.0 years; 13, 16.3% were Black), 72 played football, 4 played ice hockey, and 4 played other contact sports. Most played at the professional level (57, 71.3%). Mean time between neuropsychological testing and death was 3.9 (SD= 4.5) years. The most common reason for testing was dementia-related (43, 53.8%). Mean z-scores fell in the average psychometric range(mean z= -0.52, SD=1.5, range= -6.0 to 3.0) for executive function and the low average range for memory (mean z= -1.3, SD=1.1, range= -4.0 to 2.0). Eleven (20.4%) had impairment on 1 test and 3 (5.6%) on 2+ tests of executive functions. The most common impairment was on TMT-B (mean z= -1.77, 13 [38.2%] impaired). For memory, 13 (41.9%) had impairment on 1 test. Of the 14 who had CVLT-II, 7 were impaired (mean z= -1.33). Greater p-tau burden was associated with worse performance on CVLT-II (r= -.653, p= .02), but not TMT-B (r= .187, p>.05).
Conclusions:This study provides the first evidence for objectively-measured impairments in executive functions and memory in a sample with known, autopsy-confirmed CTE. Furthermore, p-tau burden corresponded to worse memory test performance. Examination of neuropsychological tests from medical records has limitations but can overcome shortcomings of retrospective informant reports to provide insight into the cognitive profiles associated with CTE.
1 Early Development of Adaptive Skills in Young Children with Agenesis of the Corpus Callosum: A Comparison to Monogenetic and Neurodevelopmental Conditions
- Lauren D Haisley, Lana Hantzch, Jasmin Turner, Kelly N Botteron, Stephen Dager, Annette M Estes, Lisa Flake, Heather Hazlett, Robert T Schultz, Joseph Piven, Lynn K Paul, Jed T Elison
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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. 401-402
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Objective:
Differences in adaptive functioning present early in development for many children with monogenic (Down Syndrome, Fragile X) and neurodevelopmental disorders. At this time, it is unclear whether children with ACC present with early adaptive delays, or if difficulties emerge later as functional tasks become more complex. While potential delays in motor development are frequently reported, other domains such as communication, social and daily living skills are rarely described. We used a prospective, longitudinal design to examine adaptive behavior from 6-24 months in children with ACC and compared their trajectories to those with monogenic and neurodevelopmental conditions.
Participants and Methods:Our sample included children with primary ACC (n= 27-47 depending on time point) whose caregivers completed the Vineland Adaptive Behavior Scales-Interview 3rd Edition, via phone at 6, 12, 18 and 24 months. Comparison samples (using the Vineland-2) included children with Down Syndrome (DS; n = 15-56), Fragile X (FX; n = 15-20), children at high familial likelihood for autism (HL-; n=192-280), and low likelihood (LL; no family history of autism and no developmental/behavioral diagnosis; n = 111196). A subset of the HL children received an autism diagnosis (HL+; n = 48-74). The DS group did not have an 18-month Vineland.
Results:A series of linear mixed model analyses (using maximum likelihood) for repeated measures was used to compare groups on three Vineland domains at 6, 12, 18 and 24 month timepoints). All fixed factors (diagnostic group, timepoint, and group X timepoint interaction) accounted for significant variance on all Vineland domains (p < .001). Post hoc comparisons with Bonferroni-correction examined ACC Vineland scores compared to the other diagnostic groups at each timepoint. At 6 months, parent-ratings indicated the ACC group had significantly weaker skills than the LL group in Communication and Motor domains. At 12, 18 and 24 months, ratings revealed weaker Communication, Daily Living and Motor skills in the ACC group compared to both the LL and HL- groups. Compared to the other clinical groups, the ACC group had stronger Socialization and Motor skills than Fragile X at 6 months, and at 24 months had stronger Communication and Socialization skills than both the DS and FX groups, as well as stronger Socialization than the HL+ group.
Conclusions:Compared to children with low likelihood of ASD, children with primary ACC reportedly have weaker Communication and Motor skills from 6 to 24 months, with weakness in Daily Living Skills appearing at 12 months and all differences increase with age. Compared to Fragile X, the ACC exhibited relative strengths in socialization and motor skills starting at 6 months. By 24 months, the ACC group was outperforming the monogenic groups on Socialization and Communication. In general, the ACC scores were consistent with the HL+ sample, except the ACC group had stronger Social skills at 18 and 24 months. The results clearly inform the need for early intervention in the domains of motor and language skills. Additionally, as we know that children with ACC are at increased risk for social difficulties, research is needed both using more fine-grained social-communication tools, and following children from infancy through middle childhood.
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.
Implications of capacity-limited, generative models for human vision
- Joseph Scott German, Robert A. Jacobs
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- Behavioral and Brain Sciences / Volume 46 / 2023
- Published online by Cambridge University Press:
- 06 December 2023, e391
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Although discriminative deep neural networks are currently dominant in cognitive modeling, we suggest that capacity-limited, generative models are a promising avenue for future work. Generative models tend to learn both local and global features of stimuli and, when properly constrained, can learn componential representations and response biases found in people's behaviors.
Radiofrequency ice dielectric measurements at Summit Station, Greenland
- Juan Antonio Aguilar, Patrick Allison, Dave Besson, Abby Bishop, Olga Botner, Sjoerd Bouma, Stijn Buitink, Maddalena Cataldo, Brian A. Clark, Kenny Couberly, Zach Curtis-Ginsberg, Paramita Dasgupta, Simon de Kockere, Krijn D. de Vries, Cosmin Deaconu, Michael A. DuVernois, Anna Eimer, Christian Glaser, Allan Hallgren, Steffen Hallmann, Jordan Christian Hanson, Bryan Hendricks, Jakob Henrichs, Nils Heyer, Christian Hornhuber, Kaeli Hughes, Timo Karg, Albrecht Karle, John L. Kelley, Michael Korntheuer, Marek Kowalski, Ilya Kravchenko, Ryan Krebs, Robert Lahmann, Uzair Latif, Joseph Mammo, Matthew J. Marsee, Zachary S. Meyers, Kelli Michaels, Katharine Mulrey, Marco Muzio, Anna Nelles, Alexander Novikov, Alisa Nozdrina, Eric Oberla, Bob Oeyen, Ilse Plaisier, Noppadol Punsuebsay, Lilly Pyras, Dirk Ryckbosch, Olaf Scholten, David Seckel, Mohammad Ful Hossain Seikh, Daniel Smith, Jethro Stoffels, Daniel Southall, Karen Terveer, Simona Toscano, Delia Tosi, Dieder J. Van Den Broeck, Nick van Eijndhoven, Abigail G. Vieregg, Janna Z. Vischer, Christoph Welling, Dawn R. Williams, Stephanie Wissel, Robert Young, Adrian Zink
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- Journal of Glaciology , First View
- Published online by Cambridge University Press:
- 09 October 2023, pp. 1-12
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We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
High prevalence of antibiotic use in a tertiary-care hospital in Sierra Leone: We need to handle antibiotics with care
- Ibrahim Franklyn Kamara, Bobson Fofanah, Bockarie Pharaj Sheriff, Victoria Katawera, Robert Musoke, Sulaiman Lakoh, Kadijatu Nabie Kamara, Joseph Sam Kanu
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 3 / Issue S2 / June 2023
- Published online by Cambridge University Press:
- 29 September 2023, pp. s22-s23
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Background: Antimicrobial resistance (AMR) is a global public health concern that has the potential to reverse decades of progress aimed at decreasing morbidity and mortality attributed to infectious diseases. In 2019, ~5 million deaths were associated with AMR, of which 1.2 million were attributed to antibacterial-resistant infections. Healthcare facilities where antimicrobials are frequently used are high-risk settings for the selection and spread of resistant bacteria, and they further contribute to the increase in the burden of AMR. We have documented the prevalence and indication of antibiotic use in a tertiary-care referral hospital in Freetown, Sierra Leone. Methods: This point-prevalence survey was conducted at Connaught hospital, a tertiary-care hospital in Sierra Leone, in November 2021. The hospital offers a range of medical and surgical services through 25 units and has 16 wards with >300 beds. Data on patient-level antibiotic use, including indications for use, were extracted from medical records using WHO point-prevalence survey (PPS) forms that had been pretested and validated. Data collection was conducted in all the wards over a 10-day period by trained healthcare personnel. On the day of the survey, only the medical records of patients on admission before 8:00 a.m. on that day were included in the study. Data entry, cleaning, and analysis were conducted using the WHO PPS platform. Ethical approval was obtained. Results: In total, 87 patient records were included in the survey. Most (71%) were women, and the average age was 30.6 years. The prevalence of antibiotic use was 66%, and the average number of antibiotics prescribed to patients since admission was 2. The 5 most prescribed antibiotics were metronidazole, ceftriaxone, amoxicillin and clavulanic acid, ampicillin and cloxacillin, and azithromycin. The parenteral route of drug administration was the mainstay. The most frequent indications for antibiotic prescription were community-acquired infection and surgical prophylaxis. Blood-culture requests were not ordered before the initiation of antibiotic treatment. Conclusions: This study was the first study to be conducted in Connaught hospital using the WHO PPS methodology. The survey reports a high prevalence (60%) of antibiotic use, and most treatment was done empirically. This finding is contrary to the WHO recommendation of <30% antibiotic use. This high prevalence of antibiotic use has the potential to increase the burden of AMR in the country. Therefore, there is an urgent need to strengthen Connaught hospital’s antibiotic stewardship program.
Disclosures: None
Early-life participation in cognitively stimulating activities and risk of depression and anxiety in late life
- Xinye Qiu, Andrea L. Robert, Kaleigh McAlaine, Luwei Quan, Joseph Mangano, Marc G. Weisskopf
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- Psychological Medicine / Volume 54 / Issue 5 / April 2024
- Published online by Cambridge University Press:
- 14 September 2023, pp. 962-970
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Background
Early-life stressful experiences are associated with increased risk of adverse psychological outcomes in later life. However, much less is known about associations between early-life positive experiences, such as participation in cognitively stimulating activities, and late-life mental health. We investigated whether greater engagement in cognitively stimulating activities in early life is associated with lower risk of depression and anxiety in late life.
MethodsWe surveyed former participants of the St. Louis Baby Tooth study, between 22 June 2021 and 25 March 2022 to collect information on participants' current depression/anxiety symptoms and their early-life activities (N = 2187 responded). A composite activity score was created to represent the early-life activity level by averaging the frequency of self-reported participation in common cognitively stimulating activities in participants' early life (age 6, 12, 18), each rated on a 1 (least frequent) to 5 (most frequent) point scale. Depression/anxiety symptoms were measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7). We used logistic regressions to estimate odds ratios (OR) and 95% confidence intervals (CI) of outcome risk associated with frequency of early-life activity.
ResultsEach one-point increase in the early-life composite cognitive activity score was associated with an OR of 0.54 (95% CI 0.38–0.77) for late-life depression and an OR of 0.94 (95% CI 0.61–1.43) for late-life anxiety, adjusting for age, sex, race, parental education, childhood family structure, and socioeconomic status.
ConclusionsMore frequent participation in cognitively stimulating activities during early life was associated with reduced risk of late-life depression.
Novel ENT live telehealth and live video-otoscopy clinics in remote Australia: outcomes and comparisons to traditional clinic models
- Luke M O'Neil, Margie O'Neill, Fiona Whelan, Travis Leahy, Robert Wormald, Anton D Hinton-Bayre, Joseph Ghandour, Jafri Kuthubutheen
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- Journal:
- The Journal of Laryngology & Otology / Volume 138 / Issue 3 / March 2024
- Published online by Cambridge University Press:
- 12 September 2023, pp. 253-257
- Print publication:
- March 2024
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Background
Coronavirus disease 2019 challenged the delivery of healthcare in Australia, disproportionately impacting vulnerable patients, including Aboriginal and/or Torres Strait Islander peoples and those living in remote regions. The otolaryngology service provided to remote Western Australia adapted to these barriers by altering clinical consultations to a digital model.
MethodsA review was undertaken of patients in regional Western Australia. Demographics and clinical outcomes from 20 live telehealth clinics were retrospectively reviewed and compared to 16 face-to-face clinics.
ResultsThe demographics of patients reviewed in both live telehealth and face-to-face clinics were similar, except for a larger proportion of Aboriginal and/or Torres Strait Islander patients utilising telehealth. The outcomes of patients reviewed through each model of care were comparable. Live video-otoscopy provided diagnostic quality images in 92 per cent of cases.
ConclusionThe findings of our review suggest that, despite its limitations, a large proportion of ENT patients may be safely assessed through a live telehealth model.