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53 2-Back Performance Does Not Differ Between Cognitive Training Groups in Older Adults Without Dementia
- Nicole D Evangelista, Jessica N Kraft, Hanna K Hausman, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Cheshire Hardcastle, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven DeKosky, Georg A Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric Porges, Adam J Woods
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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. 360-361
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Objective:
Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.
Participants and Methods:48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.
Results:Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).
Conclusions:After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.
2 Higher White Matter Hyperintensity Load Adversely Affects Pre-Post Proximal Cognitive Training Performance in Healthy Older Adults
- Emanuel M Boutzoukas, Andrew O’Shea, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Hanna K Hausman, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Samantha G Smith, Hyun Song, Eric C Porges, Alex Hishaw, Steven T DeKosky, Samuel S Wu, Michael Marsiske, Gene E Alexander, Ronald Cohen, Adam J Woods
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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. 671-672
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Objective:
Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.
Participants and Methods:Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.
Results:RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.
Conclusions:These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.
1 Task-Based Functional Connectivity and Network Segregation of the Useful Field of View (UFOV) fMRI task
- Jessica N Kraft, Hanna K Hausman, Cheshire Hardcastle, Alejandro Albizu, Andrew O’Shea, Nicole D Evangelista, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Eric Porges, Adam J Woods
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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. 606-607
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Interventions using a cognitive training paradigm called the Useful Field of View (UFOV) task have shown to be efficacious in slowing cognitive decline. However, no studies have looked at the engagement of functional networks during UFOV task completion. The current study aimed to (a) assess if regions activated during the UFOV fMRI task were functionally connected and related to task performance (henceforth called the UFOV network), (b) compare connectivity of the UFOV network to 7 resting-state functional connectivity networks in predicting proximal (UFOV) and near-transfer (Double Decision) performance, and (c) explore the impact of network segregation between higher-order networks and UFOV performance.
Participants and Methods:336 healthy older adults (mean age=71.6) completed the UFOV fMRI task in a Siemens 3T scanner. UFOV fMRI accuracy was calculated as the number of correct responses divided by 56 total trials. Double Decision performance was calculated as the average presentation time of correct responses in log ms, with lower scores equating to better processing speed. Structural and functional MRI images were processed using the default pre-processing pipeline within the CONN toolbox. The Artifact Rejection Toolbox was set at a motion threshold of 0.9mm and participants were excluded if more than 50% of volumes were flagged as outliers. To assess connectivity of regions associated with the UFOV task, we created 10 spherical regions of interest (ROIs) a priori using the WFU PickAtlas in SPM12. These include the bilateral pars triangularis, supplementary motor area, and inferior temporal gyri, as well as the left pars opercularis, left middle occipital gyrus, right precentral gyrus and right superior parietal lobule. We used a weighted ROI-to-ROI connectivity analysis to model task-based within-network functional connectivity of the UFOV network, and its relationship to UFOV accuracy. We then used weighted ROI-to-ROI connectivity analysis to compare the efficacy of the UFOV network versus 7 resting-state networks in predicting UFOV fMRI task performance and Double Decision performance. Finally, we calculated network segregation among higher order resting state networks to assess its relationship with UFOV accuracy. All functional connectivity analyses were corrected at a false discovery threshold (FDR) at p<0.05.
Results:ROI-to-ROI analysis showed significant within-network functional connectivity among the 10 a priori ROIs (UFOV network) during task completion (all pFDR<.05). After controlling for covariates, greater within-network connectivity of the UFOV network associated with better UFOV fMRI performance (pFDR=.008). Regarding the 7 resting-state networks, greater within-network connectivity of the CON (pFDR<.001) and FPCN (pFDR=. 014) were associated with higher accuracy on the UFOV fMRI task. Furthermore, greater within-network connectivity of only the UFOV network associated with performance on the Double Decision task (pFDR=.034). Finally, we assessed the relationship between higher-order network segregation and UFOV accuracy. After controlling for covariates, no significant relationships between network segregation and UFOV performance remained (all p-uncorrected>0.05).
Conclusions:To date, this is the first study to assess task-based functional connectivity during completion of the UFOV task. We observed that coherence within 10 a priori ROIs significantly predicted UFOV performance. Additionally, enhanced within-network connectivity of the UFOV network predicted better performance on the Double Decision task, while conventional resting-state networks did not. These findings provide potential targets to optimize efficacy of UFOV interventions.
78 BVMT-R Learning Ratio Moderates Cognitive Training Gains in Useful Field of View Task in Healthy Older Adults
- Cheshire Hardcastle, Jessica N. Kraft, Hanna K. Hausman, Andrew O’Shea, Alejandro Albizu, Nicole D. Evangelista, Emanuel Boutzoukas, Emily J. Van Etten, Pradyumna K. Bharadwaj, Hyun Song, Samantha G. Smith, Eric Porges, Steven DeKosky, Georg A. Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E. Alexander, Adam J. Woods
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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. 180-181
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Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there is variability in the level of cognitive gains after cognitive training across studies. One potential explanation for this variability could be moderating factors. Prior studies suggest variables moderating cognitive training gains share features of the training task. Learning trials of the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) recruit similar cognitive abilities and have overlapping neural correlates with the UFOV task and speed-ofprocessing/working memory tasks and therefore could serve as potential moderators. Exploring moderating factors of cognitive training gains may boost the efficacy of interventions, improve rigor in the cognitive training literature, and eventually help provide tailored treatment recommendations. This study explored the association between the HVLT-R and BVMT-R learning and the UFOV task, and assessed the moderation of HVLT-R and BVMT-R learning on UFOV improvement after a 3-month speed-ofprocessing/attention and working memory cognitive training intervention in cognitively healthy older adults.
Participants and Methods:75 healthy older adults (M age = 71.11, SD = 4.61) were recruited as part of a larger clinical trial through the Universities of Florida and Arizona. Participants were randomized into a cognitive training (n=36) or education control (n=39) group and underwent a 40-hour, 12-week intervention. Cognitive training intervention consisted of practicing 4 attention/speed-of-processing (including the UFOV task) and 4 working memory tasks. Education control intervention consisted of watching 40-minute educational videos. The HVLT-R and BVMT-R were administered at the pre-intervention timepoint as part of a larger neurocognitive battery. The learning ratio was calculated as: trial 3 total - trial 1 total/12 - trial 1 total. UFOV performance was measured at pre- and post-intervention time points via the POSIT Brain HQ Double Decision Assessment. Multiple linear regressions predicted baseline Double Decision performance from HVLT-R and BVMT-R learning ratios controlling for study site, age, sex, and education. A repeated measures moderation analysis assessed the moderation of HVLT-R and BVMT-R learning ratio on Double Decision change from pre- to post-intervention for cognitive training and education control groups.
Results:Baseline Double Decision performance significantly associated with BVMT-R learning ratio (β=-.303, p=.008), but not HVLT-R learning ratio (β=-.142, p=.238). BVMT-R learning ratio moderated gains in Double Decision performance (p<.01); for each unit increase in BVMT-R learning ratio, there was a .6173 unit decrease in training gains. The HVLT-R learning ratio did not moderate gains in Double Decision performance (p>.05). There were no significant moderations in the education control group.
Conclusions:Better visuospatial learning was associated with faster Double Decision performance at baseline. Those with poorer visuospatial learning improved most on the Double Decision task after training, suggesting that healthy older adults who perform below expectations may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes.
6 Adjunctive Transcranial Direct Current Stimulation and Cognitive Training Alters Default Mode and Frontoparietal Control Network Connectivity in Older Adults
- Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Emanuel M Boutzoukas, Andrew O’Shea, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Eric S Porges, Georg A Hishaw, Samuel Wu, Steven DeKosky, Gene E Alexander, Michael Marsiske, Ronald A Cohen, Adam J Woods
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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. 675-676
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Objective:
Aging is associated with disruptions in functional connectivity within the default mode (DMN), frontoparietal control (FPCN), and cingulo-opercular (CON) resting-state networks. Greater within-network connectivity predicts better cognitive performance in older adults. Therefore, strengthening network connectivity, through targeted intervention strategies, may help prevent age-related cognitive decline or progression to dementia. Small studies have demonstrated synergistic effects of combining transcranial direct current stimulation (tDCS) and cognitive training (CT) on strengthening network connectivity; however, this association has yet to be rigorously tested on a large scale. The current study leverages longitudinal data from the first-ever Phase III clinical trial for tDCS to examine the efficacy of an adjunctive tDCS and CT intervention on modulating network connectivity in older adults.
Participants and Methods:This sample included 209 older adults (mean age = 71.6) from the Augmenting Cognitive Training in Older Adults multisite trial. Participants completed 40 hours of CT over 12 weeks, which included 8 attention, processing speed, and working memory tasks. Participants were randomized into active or sham stimulation groups, and tDCS was administered during CT daily for two weeks then weekly for 10 weeks. For both stimulation groups, two electrodes in saline-soaked 5x7 cm2 sponges were placed at F3 (cathode) and F4 (anode) using the 10-20 measurement system. The active group received 2mA of current for 20 minutes. The sham group received 2mA for 30 seconds, then no current for the remaining 20 minutes.
Participants underwent resting-state fMRI at baseline and post-intervention. CONN toolbox was used to preprocess imaging data and conduct region of interest (ROI-ROI) connectivity analyses. The Artifact Detection Toolbox, using intermediate settings, identified outlier volumes. Two participants were excluded for having greater than 50% of volumes flagged as outliers. ROI-ROI analyses modeled the interaction between tDCS group (active versus sham) and occasion (baseline connectivity versus postintervention connectivity) for the DMN, FPCN, and CON controlling for age, sex, education, site, and adherence.
Results:Compared to sham, the active group demonstrated ROI-ROI increases in functional connectivity within the DMN following intervention (left temporal to right temporal [T(202) = 2.78, pFDR < 0.05] and left temporal to right dorsal medial prefrontal cortex [T(202) = 2.74, pFDR < 0.05]. In contrast, compared to sham, the active group demonstrated ROI-ROI decreases in functional connectivity within the FPCN following intervention (left dorsal prefrontal cortex to left temporal [T(202) = -2.96, pFDR < 0.05] and left dorsal prefrontal cortex to left lateral prefrontal cortex [T(202) = -2.77, pFDR < 0.05]). There were no significant interactions detected for CON regions.
Conclusions:These findings (a) demonstrate the feasibility of modulating network connectivity using tDCS and CT and (b) provide important information regarding the pattern of connectivity changes occurring at these intervention parameters in older adults. Importantly, the active stimulation group showed increases in connectivity within the DMN (a network particularly vulnerable to aging and implicated in Alzheimer’s disease) but decreases in connectivity between left frontal and temporal FPCN regions. Future analyses from this trial will evaluate the association between these changes in connectivity and cognitive performance post-intervention and at a one-year timepoint.
28 Factor Structure of Conventional Neuropsychological Tests and NIH-Toolbox in Healthy Older Adults
- Kailey Langer, Cheshire Hardcastle, Hanna Hausman, Jessica Kraft, Alejandro Albizu, Nicole Evangelista, Emanuel Boutzoukas, Andrew O’Shea, Emily Van Etten, Samantha Smith, Hyun Song, Pradyumna Bharadwaj, Georg Hishaw, Samuel Wu, Steven DeKosky, Gene Alexander, Eric Porges, Michael Marsiske, Ronald Cohen, Adam Woods
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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, p. 710
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The National Institutes of Health-Toolbox cognition battery (NIH-TCB) is widely used in cognitive aging studies and includes measures in cognitive domains evaluated for dimensional structure and psychometric properties in prior research. The present study addresses a current literature gap by demonstrating how NIH-TCB integrates into a battery of traditional clinical neuropsychological measures. The dimensional structure of NIH-TCB measures along with conventional neuropsychological tests is assessed in healthy older adults.
Participants and Methods:Baseline cognitive data were obtained from 327 older adults. The following measures were collected: NIH-Toolbox cognitive battery, Controlled Oral Word Association (COWA) letter and animals tests, Wechsler Test of Adult Reading (WTAR), Stroop Color-Word Interference Test, Paced Auditory Serial Addition Test (PASAT), Brief Visuospatial Memory Test (BVMT), Letter-Number Sequencing (LNS), Hopkins Verbal Learning Test (HVLT), Trail Making Test A&B, Digit Span. Hmisc, psych, and GPARotation packages for R were used to conduct exploratory factor analyses (EFA). A 5-factor solution was conducted followed by a 6-factor solution. Promax rotation was used for both EFA models.
Results:The 6-factor EFA solution is reported here. Results indicated the following 6 factors: working memory (Digit Span forward, backward, and sequencing, PASAT trials 1 and 2, NIH-Toolbox List Sorting, LNS), speed/executive function (Stroop color naming, word reading, and color-word interference, NIH-Toolbox Flanker, Dimensional Change, and Pattern Comparison, Trail Making Test A&B), verbal fluency (COWA letters F-A-S), crystallized intelligence (WTAR, NIH-Toolbox Oral Recognition and Picture Vocabulary), visual memory (BVMT immediate and delayed), and verbal memory (HVLT immediate and delayed. COWA animals and NIH-Toolbox Picture Sequencing did not adequately load onto any EFA factor and were excluded from the subsequent CFA.
Conclusions:Findings indicate that in a sample of healthy older adults, these collected measures and those obtained through the NIH-Toolbox battery represent 6 domains of cognitive function. Results suggest that in this sample, picture sequencing and COWA animals did not load adequately onto the factors created from the rest of the measures collected. These findings should assist in interpreting future research using combined NIH-TCB and neuropsychological batteries to assess cognition in healthy older adults.
40 Associations Between Cardiovascular Risk, White Matter, and Medication Predictors on Longitudinal Cognitive Change in the National Alzheimer’s Coordinating Center (NACC) Cohort
- Lindsay J Rotblatt, Jared J Tanner, Ronald A Cohen, Ann L Horgas, Michael Marsiske
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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. 349-350
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Drawing on the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS), this study aimed to investigate the direct and indirect associations between vascular risk factors/cardiovascular disease (CVD), pharmacological treatment (of CVD), and white matter hyperintensity (WMH) burden on overall cognition and decline trajectories in a cognitively diverse sample of older adults.
Participants and Methods:Participants were 1,049 cognitively diverse older adults drawn from a larger NACC data repository of 22,684 participants whose data was frozen as of December 2019. The subsample included only participants who were aged 60-97 (56.7% women) who completed at least one post-baseline neuropsychological evaluation, had medication data, and both T1 and FLAIR neuroimaging scans. Cognitive composites (Memory, Attention, Executive Function, Language) were derived factor analytically using harmonized data. Baseline WMH volumes were quantified using UBO Detector. Baseline health screening and medication data was used to determine overall CVD burden and total medication. Longitudinal latent growth curve models were estimated adjusting for demographics.
Results:More CVD medication was associated with greater CVD burden; however, no direct effects of medication were found on any of the cognitive composites or WMH volume. While no direct effects of CVD burden on cognition (overall or rate of decline) were observed, instead we found that greater CVD burden had small, but significant, negative indirect effects on Memory, Attention, Executive Functioning and Language (all p’s < .01) after controlling for CVD medication use. Whole brain WMH volume served as the mediator of this relationship, as it did for an indirect effect of baseline CVD on 6-year rate of decline in Memory and Executive function.
Conclusions:Findings from this study were generally consistent with previous literature and extend extant knowledge regarding the direct and indirect associations between CVD burden, pharmacological treatment, and neuropathology of presumed vascular origin on cognitive decline trajectories in an older adult sample. Results reveal the subtle importance of CVD risk factors on late life cognition even after accounting for treatment and WHM volume and highlight the need for additional research to determine sensitive windows of opportunity for intervention.
9 Connecting memory and functional brain networks in older adults: a resting state fMRI study
- Jori L Waner, Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel S Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric C Porges, Adam J Woods
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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. 527-528
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Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.
Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.
Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.
Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.
Strategies used for the COVID-OUT decentralized trial of outpatient treatment of SARS-CoV-2
- Nandini Avula, Dustin Kakach, Christopher J. Tignanelli, David M. Liebovitz, Jacinda M. Nicklas, Kenneth Cohen, Michael A. Puskarich, Hrishikesh K. Belani, John B. Buse, Nichole R. Klatt, Blake Anderson, Amy B. Karger, Katrina M. Hartman, Barkha Patel, Sarah L. Fenno, Neha V. Reddy, Spencer M. Erickson, David R. Boulware, Thomas A. Murray, Carolyn T. Bramante, COVID-OUT Trial Team
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- Journal of Clinical and Translational Science / Volume 7 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 07 November 2023, e242
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The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.
Coupled climate-glacier modelling of the last glaciation in the Alps
- Guillaume Jouvet, Denis Cohen, Emmanuele Russo, Jonathan Buzan, Christoph C. Raible, Wilfried Haeberli, Sarah Kamleitner, Susan Ivy-Ochs, Michael A. Imhof, Jens K. Becker, Angela Landgraf, Urs H. Fischer
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- Journal of Glaciology , First View
- Published online by Cambridge University Press:
- 06 October 2023, pp. 1-15
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Our limited knowledge of the climate prevailing over Europe during former glaciations is the main obstacle to reconstruct the past evolution of the ice coverage over the Alps by numerical modelling. To address this challenge, we perform a two-step modelling approach: First, a regional climate model is used to downscale the time slice simulations of a global earth system model in high resolution, leading to climate snapshots during the Last Glacial Maximum (LGM) and the Marine Isotope Stage 4 (MIS4). Second, we combine these snapshots and a climate signal proxy to build a transient climate over the last glacial period and force the Parallel Ice Sheet Model to simulate the dynamical evolution of glaciers in the Alps. The results show that the extent of modelled glaciers during the LGM agrees with several independent key geological imprints, including moraine-based maximal reconstructed glacial extents, known ice transfluences and trajectories of erratic boulders of known origin and deposition. Our results highlight the benefit of multiphysical coupled climate and glacier transient modelling over simpler approaches to help reconstruct paleo glacier fluctuations in agreement with traces they have left on the landscape.
207 Perceptions of the Vaccinated and Unvaccinated to Inform Translation to Health and Public Health Practice
- Part of
- Catherine Woodstock Striley, Matthew Alday, Michael Gutter, Carolina Luz Rosales, Irvin PeDro Cohen, Linda B. Cottler
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- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, p. 64
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OBJECTIVES/GOALS: Translating the science of vaccines to health and public health practice requires understanding how vaccine risks and benefits are understood and applying that knowledge to community translation. During the pandemic the lack of this knowledge became apparent. METHODS/STUDY POPULATION: Through the PACER community engagement special interest group of the ACTS, the University of Florida(UF)/Florida State University and 5 other CTSIs community engagement programs received Center for Disease Control and Prevention funding for the Program to Alleviate National Disparities in Ethnic and Minority Immunizations in the Community (PANDEMIC) to translate vaccinations into the community. At UF, HealthStreet’s Community Health Workers, CTSI Mobile Health Vehicle nurses, and Institute of Food and Agricultural Sciences extension agents collaborated to engage adults throughout the North and Central part of the state on their vaccine status and perceptions and to offer them vaccines. RESULTS/ANTICIPATED RESULTS: Through UF, 4,587 people have been interviewed in community settings using the Survey of Perceptions; 25% (1,125) had not received any COVID-19 vaccine. Among differences in perceptions, those vaccinated versus unvaccinated perceived people to be getting vaccines because they cut down on disease spread (28.9% vs. 15.2%), and perceived people NOT to be getting vaccinated because of misinformation/ignorance (27.1% vs. 11.0%) and political beliefs (16.3% vs. 6.7%). Both vaccinated and not perceived lack of trust as a reason to not get vaccinated (41.3% vs 46.4%). When asked what people were doing instead of vaccination, those vaccinated versus unvaccinated responded that people were doing nothing/very little much more often (40.6% vs. 21.8%) but were less likely to say ’trying to stay healthy’ (9.1% vs. 18.9%). DISCUSSION/SIGNIFICANCE: The science of translating from bench through clinical trials and to common health and public health practice requires knowledge of reasons for successful adoption. This survey adds to knowledge of perceptions towards vaccines that inhibit translation and biases toward the vaccine-hesitant.
68 Metformin prevents the diagnosis of Long Covid in phase 3 trial of early treatment.
- Part of
- Carolyn Bramante, Esteban Wirtz, John Buse, David Boulware, Jacinda Nicklas, David Odde, Ken Cohen, Michael Puskarich, Christopher Tignanelli, Nichole Klatt, David Leibovitz, Hrishikesh Belani
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, pp. 18-19
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OBJECTIVES/GOALS: Chronic or new symptoms after infection with severe-acute-respiratory-coronavirus-2 (SARS-CoV-2) has been termed post-acute sequelae of Covid-19 (PASC) or Long Covid. Our objective is to present results from COVID-OUT, a phase 3 double-blind, randomized controlled trial of early outpatient treatment of Covid-19 with repurposed medications. METHODS/STUDY POPULATION: COVID-OUT enrolled adults age 30 to 85 with overweight or obesity who had proof of SARS-CoV-2 infection and fewer than 7 days of symptoms. In this 2 by 3 factorial design trial of metformin, ivermectin, fluvoxamine, or exact-matching placebo of each medication, participants were randomized 1:1:1:1:1:1 to the 6 treatment allocations. This abstract focuses on whether early treatment with metformin prevented Long Covid. Immediate release metformin was titrated to 1500mg daily over the first 6 days. We assessed the incidence of clinician-diagnosed Long Covid with follow up through 10 months after enrollment. We also assessed where participants were diagnosed with Long Covid, and where they received Long Covid treatment. RESULTS/ANTICIPATED RESULTS: Of 1124 participants, 98 (8.7%) report having a healthcare provider make a diagnosis of long covid. By arm, 6.9% (39/564) of metformin participants report having a diagnosis for long covid as compared with 10.5% (59/560) of matched placebo controls. The absolute reduction attributable to metformin was 3.6% (95%CI, 0.3% to 7.0%; P=0.031) with a relative risk reduction of 34% (95%CI, 3% to 55%). The metformin cost per long covid case averted was $28 (95%CI, $15 to $306). 10-month follow-up data will be available at the time of presentation as well as an analysis of baseline factors associated with the development of Long-Covid, independent of treatment allocation in the trial. DISCUSSION/SIGNIFICANCE: Metformin reduced the incidence of clinician-diagnosed long covid by 34% in a double-blind randomized placebo-controlled trial, and previous research published in-vitro activity by metformin against SARS-CoV-2 and other RNA viruses. Further investigation of metformin as early treatment for SARS-CoV-2 is warranted.
Adapting the Evidence Academy model for virtual stakeholder engagement in a national setting during the COVID-19 pandemic
- Lori Carter-Edwards, Renee Leverty, Alicia Bilheimer, Lindsay Bailey, Bukola Adeshina, Prabisha Shrestha, Zhitong Yu, Gaurav Dave, Michael Cohen-Wolkowiez, Warren Kibbe, Giselle Corbie
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 20 March 2023, e98
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The COVID-19 pandemic raised the importance of adaptive capacity and preparedness when engaging historically marginalized populations in research and practice. The Rapid Acceleration of Diagnostics in Underserved Populations’ COVID-19 Equity Evidence Academy Series (RADx-UP EA) is a virtual, national, interactive conference model designed to support and engage community-academic partnerships in a collaborative effort to improve practices that overcome disparities in SARS-CoV-2 testing and testing technologies. The RADx-UP EA promotes information sharing, critical reflection and discussion, and creation of translatable strategies for health equity. Staff and faculty from the RADx-UP Coordination and Data Collection Center developed three EA events with diverse geographic, racial, and ethnic representation of attendees from RADx-UP community-academic project teams: February 2021 (n = 319); November 2021 (n = 242); and September 2022 (n = 254). Each EA event included a data profile; 2-day, virtual event; event summary report; community dissemination product; and an evaluation strategy. Operational and translational delivery processes were iteratively adapted for each EA across one or more of five adaptive capacity domains: assets, knowledge and learning, social organization, flexibility, and innovation. The RADx-UP EA model can be generalized beyond RADx-UP and tailored by community and academic input to respond to local or national health emergencies.
The Uncoordinated Teachers Puzzle
- Michael Cohen
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- Journal:
- Episteme , First View
- Published online by Cambridge University Press:
- 23 February 2023, pp. 1-8
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Williamson (2000) argues that the KK principle is inconsistent with knowledge of margin for error in cases of inexact perceptual observations. This paper argues, primarily by analogy to a different scenario, that Williamson's argument is fallacious. Margin for error principles describe the agent's knowledge as a result of an inexact perceptual event, not the agent's knowledge state in general. Therefore, epistemic agents can use their knowledge of margin for error at most once after a perceptual event, but not more. This insight blocks a crucial step in Williamson's original argument. Along the way, the value of standard epistemic logic for analyzing margin for error reasoning is challenged.
Processing of social and monetary rewards in autism spectrum disorders
- Sarah Baumeister, Carolin Moessnang, Nico Bast, Sarah Hohmann, Pascal Aggensteiner, Anna Kaiser, Julian Tillmann, David Goyard, Tony Charman, Sara Ambrosino, Simon Baron-Cohen, Christian Beckmann, Sven Bölte, Thomas Bourgeron, Annika Rausch, Daisy Crawley, Flavio Dell'Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Dorothea L. Floris, Vincent Frouin, Hannah Hayward, Rosemary Holt, Mark H. Johnson, Emily J. H. Jones, Meng-Chuan Lai, Michael V. Lombardo, Luke Mason, Bethany Oakley, Marianne Oldehinkel, Antonio M. Persico, Antonia San José Cáceres, Thomas Wolfers, Eva Loth, Declan G. M. Murphy, Jan K. Buitelaar, Heike Tost, Andreas Meyer-Lindenberg, Tobias Banaschewski, Daniel Brandeis, the EU-AIMS LEAP Group
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- Journal:
- The British Journal of Psychiatry / Volume 222 / Issue 3 / March 2023
- Published online by Cambridge University Press:
- 26 January 2023, pp. 100-111
- Print publication:
- March 2023
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Background
Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.
AimsUtilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
MethodFunctional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).
ResultsAcross social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.
ConclusionsOur results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
Chapter 11 - Popular Poetry
- from Part II - Forms and Formats
- Edited by Justine S. Murison, University of Illinois
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- Book:
- American Literature in Transition, 1820–1860
- Published online:
- 09 June 2022
- Print publication:
- 23 June 2022, pp 180-194
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Summary
This essay walks us through the methodological questions provoked by the popularity of poetry in the antebellum period. It urges scholars to focus less on authorial innovation and critical reception and more on readers and reading, where we find an absolute saturation of poetic enthusiasm and the traces of a transatlantic and commonplace poetic language that has been obscured by the predominance of prose in scholarship on antebellum literature.
Chapter 7 - Anonymous
- from Part I - Careers
- Edited by Cody Marrs, University of Georgia
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- Book:
- American Literature in Transition, 1851–1877
- Published online:
- 15 June 2022
- Print publication:
- 23 June 2022, pp 107-124
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Summary
Among the many, many transitions in American literature that have been attributed to the US Civil War, one of the less often noted is that the war years coincided with a decisive shift away from authorial anonymity. This transition can be observed in the publication practices of the day’s leading magazines. Harper’s, which had been started in 1850, began naming authors in the index to its twentieth volume (1860), while the Atlantic Monthly, introduced in 1857, began publishing the names of its authors in the index to its tenth volume (1862). The first series of Putnam’s, which ran in the 1850s, did not identify authors in either its issues or its volume indices, but the second series, begun in 1868, did, a distinction that holds when comparing the Continental Monthly, which ran during the war (1862–64) and never identified authors, with the Galaxy, which debuted in 1866 and always did. Even the hoary North American Review got into the act, and started attributing its authors with the January issue of 1868, after more than fifty years of never doing so. There were, of course, exceptions to this trend; antebellum periodicals like Graham’s Magazine or the Broadway Journal sometimes identified the more famous authors who contributed to their pages, while reprint journals like Littell’s Living Age (1844–96) attributed only the original publication sources of its contents, never the individual authors, even at the end of the century. In general, though, postbellum readers of American magazines would be much more likely than their antebellum forebears to know the name of the person who had written whichever article they were reading.
Clinical Policies and Procedures for Critical Care Transport during a Respiratory Pandemic
- David C. Leisten, Jennifer Wheeler, James Boomhower, Michael A. Frakes, Todd Denison, Jason E. Cohen, Susan R. Wilcox
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- Journal:
- Prehospital and Disaster Medicine / Volume 36 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 22 September 2021, pp. 762-766
- Print publication:
- December 2021
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The severe acute respiratory syndrome coronavirus disease-2 (SARS-CoV-2) pandemic of 2020-2021 created unprecedented challenges for clinicians in critical care transport (CCT). These CCT services had to rapidly adjust their clinical approaches to evolving patient demographics, a preponderance of respiratory failure, and transport utilization stratagem. Organizations had to develop and implement new protocols and guidelines in rapid succession, often without the education and training that would have been involved pre-coronavirus disease 2019 (COVID-19). These changes were complicated by the need to protect crew members as well as to optimize patient care. Clinical initiatives included developing an awake proning transport protocol and a protocol to transport intubated proned patients. One service developed a protocol for helmet ventilation to minimize aerosolization risks for patients on noninvasive positive pressure ventilation (NIPPV). While these clinical protocols were developed specifically for COVID-19, the growth in practice will enhance the care of patients with other causes of respiratory failure. Additionally, these processes will apply to future respiratory epidemics and pandemics.
13 - The Colorado River Basin
- from Part III - Engineered Rivers
- Edited by Jurgen Schmandt, Aysegül Kibaroglu
- Edited in association with Regina Buono, University of Texas, Austin, Sephra Thomas, University of Texas, Austin
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- Book:
- Sustainability of Engineered Rivers In Arid Lands
- Published online:
- 16 September 2021
- Print publication:
- 16 September 2021, pp 164-180
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Summary
The Colorado is a river in transition – a newly “closed” basin where demands have exhausted reliable supplies. Decades of often short-sighted management decisions have contributed to the crisis environment that currently surrounds the Colorado River. Over the past fifteen years, however, stakeholders and managers have enacted significant changes to the rules and regulations governing the Colorado, and additional reforms remain close to enactment. Unlike the deal-making that characterized negotiations in the twentieth century, recent efforts focus primarily on strategies to promote coordinated management, reduce consumption, and restore a more holistic watershed perspective to a river that was legally apportioned long ago among a highly complex amalgam of jurisdictions and water users. In many respects, the river management system is a successful example of adaptation to changing social and hydrological conditions. Yet, it remains an open question whether the pace and scale of reform is sufficient to deal with the basin’s future.
The relationship between simulated milrinone exposure and hypotension in children
- Sarah Jane Commander, Daniel Gonzalez, Karan R. Kumar, Tracy Spears, Michael Cohen-Wolkowiez, Kanecia O. Zimmerman, Stephen J. Balevic, Christoph P. Hornik
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- Journal:
- Cardiology in the Young / Volume 32 / Issue 5 / May 2022
- Published online by Cambridge University Press:
- 05 August 2021, pp. 782-788
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Introduction:
Hypotension is an adverse event that may be related to systemic exposure of milrinone; however, the true exposure–safety relationship is unknown.
Methods:Using the Pediatric Trials Network multicentre repository, we identified children ≤17 years treated with milrinone. Hypotension was defined according to age, using the Pediatric Advanced Life Support guidelines. Clinically significant hypotension was defined as hypotension with concomitant lactate >3 mg/dl. A prior population pharmacokinetic model was used to simulate milrinone exposures to evaluate exposure–safety relationships.
Results:We included 399 children with a median (quarter 1, quarter 3) age of 1 year (0,5) who received 428 intravenous doses of milrinone (median infusion rate 0.31 mcg/kg/min [0.29,0.5]). Median maximum plasma milrinone concentration was 110.7 ng/ml (48.4,206.2). Median lowest systolic and diastolic blood pressures were 74 mmHg (60,85) and 35 mmHg (25,42), respectively. At least 1 episode of hypotension occurred in 178 (45%) subjects; clinically significant hypotension occurred in 10 (2%). The maximum simulated milrinone plasma concentrations were higher in subjects with clinically significant hypotension (251 ng/ml [129,329]) versus with hypotension alone (86 ng/ml [44, 173]) versus without hypotension (122 ng/ml [57, 208], p = 0.002); however, this relationship was not retained on multivariable analysis (odds ratio 1.01; 95% confidence interval 0.998, 1.01).
Conclusions:We successfully leveraged a population pharmacokinetic model and electronic health record data to evaluate the relationship between simulated plasma concentration of milrinone and systemic hypotension occurrence, respectively, supporting the broader applicability of our novel, efficient, and cost-effective study design for examining drug exposure–response and –safety relationships.