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Mechanically induced localisation of SECONDARY WALL INTERACTING bZIP is associated with thigmomorphogenic and secondary cell wall gene expression
- Joshua H. Coomey, Kirk J.-M. MacKinnon, Ian W. McCahill, Bahman Khahani, Pubudu P. Handakumbura, Gina M. Trabucco, Jessica Mazzola, Nicole A. Leblanc, Rithany Kheam, Miriam Hernandez-Romero, Kerrie Barry, Lifeng Liu, Ji E. Lee, John P. Vogel, Ronan C. O’Malley, James J. Chambers, Samuel P. Hazen
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- Journal:
- Quantitative Plant Biology / Volume 5 / 2024
- Published online by Cambridge University Press:
- 03 May 2024, e5
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Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.
Head and Neck Cancer: United Kingdom National Multidisciplinary Guidelines, Sixth Edition
- Jarrod J Homer, Stuart C Winter, Elizabeth C Abbey, Hiba Aga, Reshma Agrawal, Derfel ap Dafydd, Takhar Arunjit, Patrick Axon, Eleanor Aynsley, Izhar N Bagwan, Arun Batra, Donna Begg, Jonathan M Bernstein, Guy Betts, Colin Bicknell, Brian Bisase, Grainne C Brady, Peter Brennan, Aina Brunet, Val Bryant, Linda Cantwell, Ashish Chandra, Preetha Chengot, Melvin L K Chua, Peter Clarke, Gemma Clunie, Margaret Coffey, Clare Conlon, David I Conway, Florence Cook, Matthew R Cooper, Declan Costello, Ben Cosway, Neil J A Cozens, Grant Creaney, Daljit K Gahir, Stephen Damato, Joe Davies, Katharine S Davies, Alina D Dragan, Yong Du, Mark R D Edmond, Stefano Fedele, Harriet Finze, Jason C Fleming, Bernadette H Foran, Beth Fordham, Mohammed M A S Foridi, Lesley Freeman, Katherine E Frew, Pallavi Gaitonde, Victoria Gallyer, Fraser W Gibb, Sinclair M Gore, Mark Gormley, Roganie Govender, J Greedy, Teresa Guerrero Urbano, Dorothy Gujral, David W Hamilton, John C Hardman, Kevin Harrington, Samantha Holmes, Jarrod J Homer, Deborah Howland, Gerald Humphris, Keith D Hunter, Kate Ingarfield, Richard Irving, Kristina Isand, Yatin Jain, Sachin Jauhar, Sarra Jawad, Glyndwr W Jenkins, Anastasios Kanatas, Stephen Keohane, Cyrus J Kerawala, William Keys, Emma V King, Anthony Kong, Fiona Lalloo, Kirsten Laws, Samuel C Leong, Shane Lester, Miles Levy, Ken Lingley, Gitta Madani, Navin Mani, Paolo L Matteucci, Catriona R Mayland, James McCaul, Lorna K McCaul, Pádraig McDonnell, Andrew McPartlin, Valeria Mercadante, Zoe Merchant, Radu Mihai, Mufaddal T Moonim, John Moore, Paul Nankivell, Sonali Natu, A Nelson, Pablo Nenclares, Kate Newbold, Carrie Newland, Ailsa J Nicol, Iain J Nixon, Rupert Obholzer, James T O'Hara, S Orr, Vinidh Paleri, James Palmer, Rachel S Parry, Claire Paterson, Gillian Patterson, Joanne M Patterson, Miranda Payne, L Pearson, David N Poller, Jonathan Pollock, Stephen Ross Porter, Matthew Potter, Robin J D Prestwich, Ruth Price, Mani Ragbir, Meena S Ranka, Max Robinson, Justin W G Roe, Tom Roques, Aleix Rovira, Sajid Sainuddin, I J Salmon, Ann Sandison, Andy Scarsbrook, Andrew G Schache, A Scott, Diane Sellstrom, Cherith J Semple, Jagrit Shah, Praveen Sharma, Richard J Shaw, Somiah Siddiq, Priyamal Silva, Ricard Simo, Rabin P Singh, Maria Smith, Rebekah Smith, Toby Oliver Smith, Sanjai Sood, Francis W Stafford, Neil Steven, Kay Stewart, Lisa Stoner, Steve Sweeney, Andrew Sykes, Carly L Taylor, Selvam Thavaraj, David J Thomson, Jane Thornton, Neil S Tolley, Nancy Turnbull, Sriram Vaidyanathan, Leandros Vassiliou, John Waas, Kelly Wade-McBane, Donna Wakefield, Amy Ward, Laura Warner, Laura-Jayne Watson, H Watts, Christina Wilson, Stuart C Winter, Winson Wong, Chui-Yan Yip, Kent Yip
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- Journal:
- The Journal of Laryngology & Otology / Volume 138 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 14 March 2024, pp. S1-S224
- Print publication:
- April 2024
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The Role of Personal Demands and Personal Resources in Enhancing Study Engagement and Preventing Study Burnout
- Marijntje E. L. Zeijen, Veerle Brenninkmeijer, Maria C. W. Peeters, Nicole J. J. M. Mastenbroek
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- Journal:
- The Spanish Journal of Psychology / Volume 27 / 2024
- Published online by Cambridge University Press:
- 08 March 2024, e10
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Using a 1-year longitudinal design, we examined the role of personal demands and personal resources in long-term health impairment and motivational processes among master students. Based on the job demands-resources theory and transactional model of stress, we hypothesized that students’ personal demands (i.e., irrational performance demands, awfulizing and irrational need for control) predict perceived study demands one year later, and indirectly relate to burnout. Furthermore, we predicted that personal resources indirectly associate with study engagement via students’ perceived study resources one year later. These hypotheses were tested in a sample of Dutch master students (N = 220 at T1 and T2) using structural equation modelling. As hypothesized, personal demands and personal resources at T1 predicted study demands and study resources one year later (T2, β = .25–.42, p <. 05), respectively. Study-home interference [study demand] mediated the association between personal demands and burnout (β = .08, p = .029), whereas opportunities for development [study resource] mediated the association between personal resources and study engagement (β = .08, p = .014). Hence, personal demands and personal resources relate indirectly to students’ burnout and engagement one year later via a heightened level of specific study demands and study resources. Accordingly, the present research expands the propositions of the JD-R Theory by proposing personal demands as a relevant factor for students’ long-term well-being.
Adherence to the healthy eating index-2010 and alternative healthy eating index-2010 in relation to metabolic syndrome among African Americans in the Jackson heart study
- Nicole K Reeder, Jennifer C Reneker, Bettina M Beech, Marino A Bruce, Elizabeth Heitman, Keith C Norris, Sameera A Talegawkar, Roland J Thorpe, Jr
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- Journal:
- Public Health Nutrition / Volume 27 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 16 February 2024, e74
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Objective:
The primary objective of this study was to determine whether Healthy Eating Index (HEI) and Alternative Healthy Eating Index (AHEI) scores were associated with incident metabolic syndrome.
Design:This study is a secondary analysis of data from the Jackson Heart Study. HEI and AHEI scores were divided into quintiles and Cox proportional hazards regression models were analysed for 1864 African American adults free from metabolic syndrome at Exam 1 to examine the incidence of metabolic syndrome by quintile of dietary quality score.
Setting:Hinds, Madison and Rankin counties, Mississippi, USA.
Participants:African American adults, ages 21–94 years, 60·9 % female.
Results:Over a mean follow-up time of 6·7 years, we observed 932 incident cases of metabolic syndrome. After adjusting for multiple covariates, a higher HEI score at Exam 1 was not associated with the risk of incident metabolic syndrome, except when looking at the trend analysis for the subgroup of adults with two metabolic syndrome components at Exam 1 (P-trend = 0·03). A higher AHEI score at Exam 1 was associated with the risk of incident metabolic syndrome (hazard ratio for those in the highest quintile compared to the lowest: 0·80 (95 % CI: 0·65, 0·99), P-trend = 0·03).
Conclusion:These findings suggest that a dietary pattern that scores higher on the AHEI may help reduce the risk of metabolic syndrome, even for adults who already have two of the minimum of three components required for a diagnosis of metabolic syndrome.
Primary care practice-based interventions and their effect on participation in population-based cancer screening programs: a systematic narrative review
- Ebony J. Verbunt, Grace Newman, Nicola S. Creagh, Kristi M. Milley, Jon D. Emery, Margaret A. Kelaher, Nicole M. Rankin, Claire E. Nightingale
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- Journal:
- Primary Health Care Research & Development / Volume 25 / 2024
- Published online by Cambridge University Press:
- 12 February 2024, e12
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Aim:
To provide a systematic synthesis of primary care practice-based interventions and their effect on participation in population-based cancer screening programs.
Background:Globally, population-based cancer screening programs (bowel, breast, and cervical) have sub-optimal participation rates. Primary healthcare workers (PHCWs) have an important role in facilitating a patient’s decision to screen; however, barriers exist to their engagement. It remains unclear how to best optimize the role of PHCWs to increase screening participation.
Methods:A comprehensive search was conducted from January 2010 until November 2023 in the following databases: Medline (OVID), EMBASE, and CINAHL. Data extraction, quality assessment, and synthesis were conducted. Studies were separated by whether they assessed the effect of a single-component or multi-component intervention and study type.
Findings:Forty-nine studies were identified, of which 36 originated from the USA. Fifteen studies were investigations of single-component interventions, and 34 studies were of multi-component interventions. Interventions with a positive effect on screening participation were predominantly multi-component, and most included combinations of audit and feedback, provider reminders, practice-facilitated assessment and improvement, and patient education across all screening programs. Regarding bowel screening, provision of screening kits at point-of-care was an effective strategy to increase participation. Taking a ‘whole-of-practice approach’ and identifying a ‘practice champion’ were found to be contextual factors of effective interventions.
The findings suggest that complex interventions comprised of practitioner-focused and patient-focused components are required to increase cancer screening participation in primary care settings. This study provides novel understanding as to what components and contextual factors should be included in primary care practice-based interventions.
Aggressive behaviours associated with MDMA and psychedelics: a narrative review
- Negar Sayrafizadeh, Nicole Ledwos, M. Ishrat Husain, David J. Castle
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- Journal:
- Acta Neuropsychiatrica , First View
- Published online by Cambridge University Press:
- 08 February 2024, pp. 1-13
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Objective:
Monoamine neurotransmitters play a role in aggression, especially when altered by illicit substances. However, some literature suggests that not all illicit substances may lead to aggression, notably psychedelics. This narrative review investigates the associations between serotonergic psychedelics and MDMA on aggressive behaviour.
Methods:PubMed and PsycINFO were searched for original, peer-reviewed articles evaluating the effects of serotonergic psychedelics and 3,4-methyl enedioxy methamphetamine (MDMA) on violent and aggressive behaviour using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results:After removing duplicates, a total of 555 articles were screened, with 16 meeting the inclusion criteria. One additional article was obtained through reference screening bringing the total to 17 articles. Of these 17 articles, 14 studies focused on MDMA and three on serotonergic psychedelics. Findings were mixed, with some results demonstrating increased aggression following psychedelics and others suggesting protective effects. Limitations in the current literature include varied definitions of psychedelics, lack of standardised objective outcome measures and failure to control for confounding.
Conclusion:As psychedelic research continues to expand, further assessment on the effects of serotonergic psychedelics and MDMA on aggressive behaviour is required.
Aflatoxin B1 Sorption and Safety of Dietary Sodium Bentonite in Sprague-Dawley Rats
- Alicia G. Marroquín-Cardona, Youjun Deng, Jose F. Garcia-Mazcorro, Natalie M. Johnson, Nicolle J. Mitchell, Lili Tang, Jia-Sheng Wang, Roger B. Harvey, Timothy D. Phillips
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- Journal:
- Clays and Clay Minerals / Volume 70 / Issue 2 / April 2022
- Published online by Cambridge University Press:
- 01 January 2024, pp. 165-181
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Bentonites are readily available clays used in the livestock industry as feed additives to reduce aflatoxin (AF) exposure; their potential interaction with nutrients is the main concern limiting their use, however. The objective of the present study was to determine the safety of a dietary sodium-bentonite (Na-bentonite) supplement as a potential AF adsorbent, using juvenile Sprague Dawley (SD) rats as a research model. Animals were fed either a control diet or a diet containing Na-bentonite at 0.25% and 2% (w/w) inclusion rate. Growth, serum, and blood biochemical parameters, including selected serum vitamins (A and E) and elements such as calcium (Ca), potassium (K), iron (Fe), and zinc (Zn) were measured. The mineral characteristics and the aflatoxin B1 sorption capacity of Na-bentonite were also determined. By the end of the study, males gained more weight than females in control and Na-bentonite groups (p ≤ 0.0001); the interaction between treatment and sex was not significant (p = 0.6780), however. Some significant differences between the control group and bentonite treatments were observed in serum biochemistry and vitamin and minerals measurements; however, parameters fell within reference clinical values reported for SD rats and no evidence of dose-dependency was found. Serum Na and Na/K ratios were increased, while K levels were decreased in males and females from Na-bentonite groups. Serum Zn levels were decreased only in males from Na-bentonite treatments. Overall, results showed that inclusion of Na-bentonite at 0.25% and 2% did not cause any observable toxicity in a 3-month rodent study.
33 Does Comorbid Depression Impact Executive Functioning (EF) in Adults Diagnosed with ADHD?: A Comparison of EF Across Diagnoses in Clinically-Referred Individuals
- Haley V. Skymba, Gabriel P. Ovsiew, Nicole M. Durkin, Kyle J. Jennette, Zachary J. Resch, Jason R. Soble
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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. 640-641
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Objective:
Neurobiological and cognitive theories implicate deficits in executive function (EF) as a core facet of both depressive disorders and attention-deficit/hyperactivity disorder (ADHD), but empirical investigations inconsistently support this conclusion. Despite recognition of the likely bi-directional relationship of EF deficits to depression and ADHD, respectively, the extent to which comorbid depression might impact EF in adults remains unclear, considering more of the literature has examined children and adolescents. This study examined performance differences on EF measures in clinically-referred adults diagnosed with ADHD or a non-ADHD primary psychopathological condition in the presence/absence of comorbid depression.
Participants and Methods:This cross-sectional study included data from 404 adults referred for neuropsychological evaluation at a Midwestern academic medical center. In total, 343 met DSM-5 diagnostic criteria for ADHD (ADHD-all group:164 Predominantly Inattentive presentation [ADHD-I] and 179 Combined presentation [ADHD-C]) and 61 met criteria for a non-ADHD primary psychopathological condition (psychopathology group: 31 mood disorder, 17 anxiety disorder, and 13 posttraumatic stress disorder) when assessed via semi-structured clinical interview. All patients completed the Beck Depression Inventory-Second Edition (BDI-II) and five EF tests: Letter Fluency, Trail Making Test-Part B (Trails-B), Stroop Color and Word Test Color-Word trial (SCWT CW); and WAIS-IV Working Memory Index (WMI). Oneway MANOVAs assessed for significant EF differences between groups with high (BDI-II greater than or equal to 20) or low (BDI-II less than or equal to 19) depressive symptoms.
Results:When group diagnosis (ADHD-all vs. psychopathology) was examined in the context of high or low depression, a significant difference in EF performance emerged between groups, F(12, 1042.72)=2.44, p<.01, Wilk's A=.93, partial n2=.02, with univariate analyses indicating a significant difference in FAS-T between at least two of the groups (F(3, 397)=3.92 , p< .01, partial n2=.03). Tukey's HSD Test for multiple comparisons found that the mean value of FAS-T was significantly different between the ADHD-high depression and ADHD-low depression groups (p=.046 , 95% CI = [5.81, -.04]) as well as between the ADHD-low depression and psychopathology-high depression groups (p=.05, 95% CI = [-8.89, .00]). A one-way MANOVA examining differences between groups when distinguishing ADHD by subtype revealed a statistically significant difference in EF performance between groups, F(20, 1301)=1.85, p<.05, Wilk's A=.91, partial n2=.02, with univariate analyses indicating a statistically significant difference in FAS-T between at least two of the groups (F(5, 395) = 2.39 , p<.05, partial n2 = .03). However, Tukey's HSD Test for multiple comparisons found that the mean value of FAS-T was not significantly different between any of the groups.
Conclusions:Overall, results indicate that clinically-referred patients with ADHD perform comparably on tests of EF regardless of the presence or absence of comorbid depression. These findings have implications for conceptualizing EF weaknesses in neuropsychological profiles for individuals with ADHD and suggest examining factors beyond comorbid depression.
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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Objective:
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.
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:
- 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.
93 Acceptability and Usability of Tablet-Based Neuropsychological Tests among South African and Ugandan Adolescents With and Without HIV
- Christopher M Ferraris, Rebecca Dunayev, Nour Kanaan, Courtney E Kirsch, Corey Morrison, Nana Asiedu, Daphne Tsapalas, Anthony F Santoro, Nicole J Phillips, Jacqueline Hoare, Angel Nanteza, Joy L Gumikiriza-Onoria, Victor Musiime, Sahera Dirajlal-Fargo, Reuben N Robbins
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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. 495-496
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Objective:
Neuropsychological (NP) tests are increasingly computerized, which automates testing, scoring, and administration. These innovations are well-suited for use in resource-limited settings, such as low- to middle- income countries (LMICs), which often lack specialized testing resources (e.g., trained staff, forms, norms, equipment). Despite this, there is a dearth of research on their acceptability and usability which could affect performance, particularly in LMICs with varying levels of access to computer technology. NeuroScreen is a tablet-based battery of tests assessing learning, memory, working memory, processing speed, executive functions, and motor speed. This study evaluated the acceptability and usability of NeuroScreen among two groups of LMIC adolescents with and without HIV from Cape Town, South Africa and Kampala, Uganda.
Participants and Methods:Adolescents in Cape Town (n=131) and Kampala (n=80) completed NeuroScreen and questions about their use and ownership of, as well as comfort with computer technology and their experiences completing NeuroScreen. Participants rated their technology use -comfort with and ease-of-use of computers, tablets, smartphones, and NeuroScreen on a Likert-type scale: (1) Very Easy/Very Comfortable to (6) Very Difficult/Very Uncomfortable. For analyses, responses of Somewhat Easy/Comfortable to Very Easy/Comfortable were collapsed to codify comfort and ease. Descriptive statistics assessed technology use and experiences of using the NeuroScreen tool. A qualitative question asked how participants would feel receiving NeuroScreen routinely in the future; responses were coded as positive, negative, or neutral (e.g., “I would enjoy it”). Chi-squares assessed for group differences.
Results:South African adolescents were 15.42 years on average, 50.3% male, and 49% were HIV-positive. Ugandan adolescents were 15.64 years on average, 50.6% male, and 54% HIVpositive. South African participants were more likely than Ugandan participants to have ever used a computer (71% vs. 49%; p<.005), or tablet (58% vs. 40%; p<.05), whereas smartphone use was similar (94% vs 87%). South African participants reported higher rates of comfort using a computer (86% vs. 46%; p<.001) and smartphone (96% vs. 88%; p<.05) compared to Ugandan participants. Ugandan adolescents rated using NeuroScreen as easier than South African adolescents (96% vs. 87%; p<.05).). Regarding within-sample differences by HIV status, Ugandan participants with HIV were less likely to have used a computer than participants without HIV (70% vs. 57%; p<.05, respectively).The Finger Tapping test was rated as the easiest by both South African (73%) and Ugandan (64%) participants. Trail Making was rated as the most difficult test among Ugandan participants (37%); 75% of South African participants reported no tasks as difficult followed by Finger Tapping as most difficult (8%). When asked about completing NeuroScreen at routine doctor’s visits, most South Africans (85%) and Ugandans (72%) responded positively.
Conclusions:This study found that even with low prior tablet use and varying levels of comfort in using technology, South African and Ugandan adolescents rated NeuroScreen with high acceptability and usability. These data suggest that scaling up NeuroScreen in LMICs, where technology use might be limited, may be appropriate for adolescent populations. Further research should examine prior experience and comfort with tablets as predictors NeuroScreen test performance.
66 Omega-3 Fatty Acids, Cognition, and Brain Volume in Healthy Elderly Adults
- Spencer K Loong, Shilpy Chowdhury, Tori Togashi, Nicole M Gatto, Samuel Barnes, Grace J Lee
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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. 372
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Objective:
One common concern amongst the aging population is that of worsening memory. Speed of processing and executive functions are also areas of age-related decline that affect daily living. Lifestyle modifications such as diet, exercise, and sleep have garnered intense interest as potential methods to prevent or delay cognitive decline. Among dietary factors, omega-3 fatty acids (FAs) have been documented as containing a myriad of health benefits, including neuroprotective effects. The aim of this study is to examine the associations between omega-3 FAs, cognitive function, and neuroanatomical regions of interest in a healthy aging population.
Participants and Methods:Adults aged 65 and older (n=40, 48.9% Female) were recruited for the Loma Linda University Adventist Health Study-2 Cognitive and Neuroimaging Substudy. Participants had a mean age of 76.25 years (SD=8.29), 16.78 years of education (SD=2.53), and were predominantly White (85.0%). Participants received a two-hour neurocognitive battery, including measures of immediate and delayed memory (Rey Auditory Verbal Learning Test, RAVLT; WMS-IV Logical Memory, LM), processing speed (Stroop), and executive functions (Stroop Color/Word). Participants underwent brain imaging on a 3T Siemens MRI, including a 3D T1-weighted MPRAGE sequence. Cortical reconstruction and volumetric segmentation were performed using FreeSurfer software. Blood samples were collected for fatty acid analysis. Individual FAs were expressed as a percent of total FAs. An omega-3 index was constructed as the sum of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) FAs. Correlational analyses, controlling for age, sex, and education, investigated relationships between omega-3 levels (individual and index) and (a) cognitive function (immediate and delayed memory, processing speed, executive functions), and (b) brain volumes in specific regions of interest (hippocampus, entorhinal cortex, frontal pole, white matter).
Results:EPA was significantly positively correlated with Stroop Color (r=.34, p=.048). Although not statistically significant, trends were observed between the omega-3 index and Stroop Color (r=.30, p=.08), and between both DHA and the omega-3 index with RAVLT – delayed recall (r=.29, p=.095; r=.30, p=.08, respectively). With regards to regional brain volumes, EPA and the omega-3 index were both significantly positively correlated with the entorhinal cortex (r=.34, p=.041; r=.41, p=.01, respectively) and white matter volume (r=.36, p=.028; r=.34, p=.038, respectively). DHA was significantly positively correlated with white matter volume (r=.34, p=.044).
Conclusions:Blood levels of EPA were positively correlated with a measure of processing speed, and trends were observed between DHA, the omega-3 index and[GN1] verbal memory, and between the omega-3 index and processing speed. We also found that omega-3 FA values were associated with greater brain volume in the entorhinal cortex and white matter in our sample of healthy older adults. Atrophy of the entorhinal cortex has been associated with pathological processes. Additionally, white matter is known to effect processing speed. These findings may offer support for the idea that omega-3 FAs exert their neuroprotective effects by fortifying areas of the brain, specifically the entorhinal cortex and white matter, that promote maintenance of cognitive function in late life.
6 Racial Discrimination and White Matter Integrity Among Black Older Adults
- Jordan D Palms, Mohamad J. Alshikho, Patrick J. Lao, Clarissa D. Morales, Jennifer J. Manly, Nicole Schupf, Adam M. Brickman, Laura B. Zahodne
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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. 788-789
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Objective:
Non-Hispanic Black older adults experience a disproportionate burden of Alzheimer’s Disease and related dementias (ADRD) risk compared to non-Hispanic White older adults. It is necessary to identify mechanisms that may be contributing to inequities in cognitive aging. Psychosocial stressors that disproportionately affect Black adults (e.g., discrimination) have the potential to impact brain health through stress pathways. The brain’s white matter, which appears to be particularly important for ADRD risk among Black older adults, may be uniquely vulnerable to stress-related physiological dysfunction. To further understand whether and how discrimination can affect ADRD risk, this study aimed to examine associations between multiple forms of racial discrimination and white matter integrity, operationalized through diffusion tensor imaging.
Participants and Methods:Cross-sectional data were obtained from 190 non-Hispanic Black residents aged 65+ without dementia in northern Manhattan. Racial discrimination was self-reported using the Everyday Discrimination and Major Experiences of Lifetime Discrimination scales. Example items from the Everyday Discrimination Scale include: “You are treated with less respect than other people”; “You are called names or insulted.” Example items from the Major Experiences of Lifetime Discrimination Scale include: “At any time in your life, have you ever been unfairly fired from a job?”; “Have you ever been unfairly denied a bank loan?” Racial discrimination was operationalized as experiences attributed to “race” or “skin color.” White matter integrity was assessed using fractional anisotropy (FA) via diffusion tensor imaging. Multivariable regression models evaluated the unique effects of everyday and major experiences of lifetime racial discrimination on mean FA in the whole brain and specific regions. Initial models controlled for age, sex/gender, intracranial volume, and white matter hyperintensities. Subsequent models additionally controlled for socioeconomic and health factors to consider potential confounders or mediators of the relationship between discrimination and white matter integrity.
Results:Major experiences of lifetime discrimination were negatively associated with mean FA within the left cingulum cingulate gyrus and the right inferior fronto-occipital fasciculus. These associations persisted when controlling for additional covariates (i.e., education, depression, and cardiovascular diseases). In contrast, major experiences of lifetime discrimination were positively associated with mean FA within the right superior longitudinal fasciculus (temporal part). This association was attenuated when controlling for additional covariates. Everyday racial discrimination was not associated with mean FA in any regions.
Conclusions:These results extend prior work linking racial discrimination to brain health and provide evidence for both risk and resilience among Black older adults. Major experiences of lifetime racial discrimination, a proxy for institutional racism, may have a stronger effect on white matter integrity than everyday racial discrimination, a proxy for interpersonal racism. Educational opportunities and cardiovascular risk factors may represent mediators between racial discrimination and white matter integrity. White matter integrity within specific brain regions may be a mechanism through which racially patterned social stressors contribute to racial disparities in ADRD. Future research should characterize within-group heterogeneity in order to identify factors that promote resilience among Black older adults.
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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Objective:
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.
4 Associations Between Education, Emotional and Instrumental Support, and Cognitive Function in Black, White, and Latinx Older Adults
- Kiara A. Baker, A. Zarina Kraal, Laura B. Zahodne, Nicole Schupf, Adam M. Brickman, Jennifer J. Manly
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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. 88-89
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Objective:
Higher education is strongly associated with better cognitive function in older adults. Previous research has also showed that positive psychosocial factors, such as selfefficacy and emotional and instrumental support, are beneficial for late-life cognition. There is prior evidence of a buffering effect of self-efficacy on the relationship between educational disadvantage and poor cognition in older adults, however it is not known if other psychosocial factors modify the schooling-cognition relationship. We hypothesized that higher levels of emotional and instrumental support will diminish the association between lower education and lower cognitive test scores among older adults.
Participants and Methods:553 older adults without dementia (42.1% non-Latinx Black, 32.2% non-Latinx White, 25.7% Latinx; 63.2% women; average age 74.4 (SD 4.3)) from the Washington Heights-Inwood Columbia Aging Project. Neuropsychological tests assessed four cognitive domains (language, memory, psychomotor processing speed, and visuospatial function). Self-reported emotional and instrumental support were assessed with measures from NIH Toolbox. Linear regression estimated interactions between education and the two support measures on cognition in models stratified by cognitive domain and racial and ethnic group. Covariates included age, sex/gender, and chronic health conditions (e.g. heart disease, stroke, cancer, etc.).
Results:Education was associated with cognition across racial and ethnic groups. For every one year of schooling, the processing speed z-score composite was 0.33 higher among Latinx participants, 0.10 among non-Latinx Black participants, and 0.03 higher among non-Latinx White participants. The education-cognition relationship was generally similar across cognitive domains with larger effects in non-Latinx Black and Latinx participants than in White participants. Low education was associated with slower processing speed among Black participants with low emotional support (B = 0.224, 95% CI [0.014, 0.096]), but there was no association between low education and processing speed among Black older adults with high levels of emotional support (beta for interaction = -.142, 95% CI [-0.061, -0.001]). A similar pattern of results was observed for instrumental support (beta for interaction = -.207, 95% CI [-0.064, 0.010]). There were no interactions between support and education on other cognitive domains or among Latinx and White participants.
Conclusions:We found that higher levels of emotional and instrumental support attenuate the detrimental effect of educational disadvantages on processing speed in older Black adults. This may occur via benefits of social capital, which provides access to health resources and knowledge, increased social interaction, an emotional outlet allowing the ability to better cope with stress. Longitudinal analyses are needed to examine temporal patterns of associations. In addition, improving equitable access to high quality schools will improve later-life cognitive outcomes for future generations of older adults. However, for the growing number of Black older adults who will not experience the benefits of structural improvements in the education system, emotional and instrumental support may represent a modifiable psychosocial factor to reduce their disproportionate burden of cognitive morbidity.
Utility of a pharmacist-managed Anticoagulation Program in patients with congenital heart disease
- Meredith J. O’Neil, BreAnn N. Garr, Jenna M. Faircloth, Julie A. Ciambarella, Adam M. Lubert, Nicole L. Nelson, David S. Cooper
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- Cardiology in the Young / Volume 34 / Issue 3 / March 2024
- Published online by Cambridge University Press:
- 08 September 2023, pp. 628-633
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Background:
Warfarin remains the preferred anticoagulant for many patients with CHD. The complexity of management led our centre to shift from a nurse-physician-managed model with many providers to a pharmacist-managed model with a centralized anticoagulation team. We aim to describe the patient cohort managed by our Anticoagulation Program and evaluate the impact of implementation of this consistent, pharmacist-managed model on time in therapeutic range, an evidence-based marker for clinical outcomes.
Methods:A single-centre retrospective cohort study was conducted to evaluate the impact of the transition to a pharmacist-managed model to improve anticoagulation management at a tertiary pediatric heart centre. The percent time in therapeutic range for a cohort managed by both models was compared using a paired t-test. Patient characteristics and time in therapeutic range of the program were also described.
Results:After implementing the pharmacist-managed model, the time in therapeutic range for a cohort of 58 patients increased from 65.7 to 80.2% (p < .001), and our Anticoagulation Program consistently maintained this improvement from 2013 to 2022. The cohort of patients managed by the Anticoagulation Program in 2022 included 119 patients with a median age of 24 years (range 19 months–69 years) with the most common indication for warfarin being mechanical valve replacement (n = 81, 68%).
Conclusions:Through a practice change incorporating a collaborative, centralized, pharmacist-managed model, this cohort of CHD patients on warfarin had a fifteen percent increase in time in therapeutic range, which was sustained for nine years.
Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial
- Muhammad Ishrat Husain, Daniel M. Blumberger, David J. Castle, Nicole Ledwos, Elise Fellows, Brett D. M. Jones, Abigail Ortiz, Stefan Kloiber, Wei Wang, Joshua D. Rosenblat, Benoit H. Mulsant
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- Journal:
- BJPsych Open / Volume 9 / Issue 4 / July 2023
- Published online by Cambridge University Press:
- 25 July 2023, e134
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Background
Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone.
AimsTo conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone).
MethodIn a 4-week, three-arm, ‘double dummy’ trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure.
ResultsThis trial will advance the understanding of psilocybin's mechanism of antidepressant action.
ConclusionsThis line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.
Exploring Constraints to Well-Being for Older Adults in Transition Into an Assisted Living Home: A Qualitative Study
- Kaitlin E. Mueller, Marieke Van Puymbroeck, Brandi M. Crowe, Nicole J. Davis
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- Canadian Journal on Aging / La Revue canadienne du vieillissement / Volume 42 / Issue 4 / December 2023
- Published online by Cambridge University Press:
- 13 July 2023, pp. 688-695
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Transitions into an assisted living home (ALH) are difficult and may impact the well-being of older adults. A thematic analysis guided by grounded theory was employed to better understand how a transition into an ALH influenced older adults’ overall well-being. Individual, face-to-face interviews were conducted with a convenience sample of 14 participants at an ALH in the rural, southeastern U.S. Two central findings that influenced well-being during the transition process were revealed: loss of independence (sub-themes include loss of physical and mental health and loss of driving) and downsizing in space and possessions. The themes support and broaden the Hierarchical Leisure Constraints Theory, a Modified Constraints to Wellbeing model is proposed, and implications for older adult health care practitioners in ALHs are recommended. Further research is needed on the Modified Constraints to Wellbeing model and how to better describe these constraints to older adults’ well-being when relocating into ALHs.