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Antibiotic overprescribing remains common in pediatric outpatient care. We evaluated Medicaid claims–based provider report cards as a scalable stewardship tool. Quarterly audit and feedback improved guideline concordance, diagnostic appropriateness, and reduced cefdinir use; highlighting claims-based electronic feedback as a sustainable outpatient antimicrobial stewardship strategy suitable for statewide implementation.
Why did some early cities thrive for centuries, while others collapsed after a short time? Archaeologists and historians are trying to identify the factors responsible for early urban resilience. This knowledge may hold insights for our understanding how cities today can best adapt to the disruptions caused by climate change. I single out two current research directions: shocks and persistence. A focus on individual cities reveals the responses of cities to specific types of shock, while a consideration of the lengths of occupation of cities and settlements (persistence through time) identifies those cities most successful in the long run.
Technical Summary
Because they offer deep temporal perspectives, the historical and archaeological records of past cities have potential to make unique contributions to the scientific understanding of urban resilience and urban adaptations to climate change today. I single out two ways that archaeologists and historians have begun to explore this potential for early cities: shocks and persistence. The responses of urban residents and institutions to diverse types of shock is a kind of specified resilience (i.e., resilience to what, who, when, and where) that can be studied for some well-documented early cities. I use the example of ancient earthquakes to discuss this theme. The temporal persistence of cities over time, on the other hand, provides insights into the general resilience of early cities by differentiating between cities that were more and less successful over the long run. I use the example of archaeological survey projects to illustrate persistence analysis, a new approach in archaeology. These two approaches build on current efforts in the fields of resilience and urban adaptations to address the importance of disturbances and deep temporal perspectives.
Social Media Summary
Archaeologists and historians can study ancient urban resilience by focusing on specific shocks and the longevity of cities.
The Family Adaptation study, ancillary to the Single Ventricle Reconstruction Trial, examined the prevalence of anxiety and its associations with stress, psychosocial factors, and quality of life measures in parents of infants who underwent the Norwood procedure.
Materials and methods:
Two hundred and fifteen parents (143 mothers and 72 fathers) of 146 infants completed state anxiety (State Anxiety Inventory), stress, psychosocial, and quality of life measures post-Norwood, post-Stage II, and at a final visit (median child age: 14 months).
Results:
A substantial proportion of parents reported severe anxiety symptoms following the Norwood surgery, with 61% of mothers and 43% of fathers affected, decreasing over time to 46% and 33% by the final visit, respectively. Mothers’ average STAI-S scores were significantly higher than fathers’ post-Norwood (47.7 ± 13.2 versus 43.5 ± 11.8, p = 0.03), declining to 42.1 ± 13.0 versus 39.0 ± 9.6 (p = 0.14) at the final visit. Stress related to parenting a child with a serious illness was a stronger and more consistent predictor of mothers’ anxiety over time (highest R2 = 0.49 for emotional distress), whereas insufficient coping and fewer protective factors were greater and more consistent predictors for fathers (highest R2 = 0.40 for mastery and health). Quality of life was a consistent predictor of state anxiety for both mothers and fathers.
Conclusion:
Anxiety is elevated in parents of infants who underwent the Norwood procedure and is influenced by a complex interplay of stress, psychosocial factors, and quality of life. Addressing these factors is crucial for improving parents’ mental health, which in turn promotes the well-being of the entire family.
Adapting to a global urban future requires diverse, long-term perspectives on urbanism. URBank supports this by bringing together global deep-time urban datasets in a modern open-science computing platform. Its design eschews checklist definitions of cities, representing the variability of past urbanism and enabling systematic comparative spatiotemporal research.
The extent to which continental acidity during the Early Triassic varied with latitude remains insufficiently constrained, despite its relevance for understanding environmental stress and biotic recovery patterns across the Smithian–Spathian boundary (SSB). We examined the abundance, textures and compositions of strontium-rich hydrated aluminium phosphate–sulphate (APS) minerals in 179 continental samples spanning tropical to high paleolatitudes in both hemispheres. APS minerals display broadly comparable early-diagenetic features across sections, indicating formation shortly after deposition under acidic meteoric conditions. Their distribution suggests a latitudinal trend: APS contents commonly exceed 0.1 vol.% in equatorial western peri-Tethyan basins, where faunal and floral records are sparse during the SSB, whereas concentrations decrease towards higher latitudes and are rare beyond ∼40° in both hemispheres. This pattern does not appear to correlate with lithological or textural variability and may reflect spatial differences in the intensity or duration of acidification linked to Siberian Traps volcanism. Equatorial basins thus likely experienced more prolonged or recurrent acidic episodes, whereas higher-latitude areas may have been subject to comparatively attenuated effects, potentially contributing to earlier ecological recovery. These results provide a useful framework for evaluating continental acidification and its environmental implications during the interval following the end-Permian mass extinction (EPME).
Paleontology provides insights into the history of the planet, from the origins of life billions of years ago to the biotic changes of the Recent. The scope of paleontological research is as vast as it is varied, and the field is constantly evolving. In an effort to identify “Big Questions” in paleontology, experts from around the world came together to build a list of priority questions the field can address in the years ahead. The 89 questions presented herein (grouped within 11 themes) represent contributions from nearly 200 international scientists. These questions touch on common themes including biodiversity drivers and patterns, integrating data types across spatiotemporal scales, applying paleontological data to contemporary biodiversity and climate issues, and effectively utilizing innovative methods and technology for new paleontological insights. In addition to these theoretical questions, discussions touch upon structural concerns within the field, advocating for an increased valuation of specimen-based research, protection of natural heritage sites, and the importance of collections infrastructure, along with a stronger emphasis on human diversity, equity, and inclusion. These questions offer a starting point—an initial nucleus of consensus that paleontologists can expand on—for engaging in discussions, securing funding, advocating for museums, and fostering continued growth in shared research directions.
To estimate the cost-effectiveness of methicillin-resistant Staphylococcus aureus (MRSA) nares poymerase chain reaction (PCR) use in pediatric pneumonia and tracheitis.
Methods:
We built a cost-effectiveness model based on MRSA prevalence and probability of empiric treatment for MRSA pneumonia or tracheitis, with all parameters varied in sensitivity analyses. The hypothetical patient cohort was <18 years of age and hospitalized in the pediatric intensive care unit for community-acquired pneumonia (CAP) or tracheitis. Two strategies were compared: MRSA nares PCR-guided antibiotic therapy versus usual care. The primary measure was cost per incorrect treatment course avoided. Length of stay and hospital costs unrelated to antibiotic costs were assumed to be the same regardless of PCR use. Both literature data and expert estimates informed sensitivity analysis ranges.
Results:
When estimating the health care system willingness-to-pay threshold for PCR testing as $140 (varied in sensitivity analyses) per incorrect treatment course avoided, reflecting estimated additional costs of MRSA targeted antibiotics, and MRSA nares PCR true cost as $64, PCR testing was generally favored if empiric MRSA treatment likelihood was >52%. PCR was not favored in some scenarios when simultaneously varying MRSA infection prevalence and likelihood of MRSA empiric treatment. Screening becomes less favorable as MRSA PCR cost increased to the highest range value of the parameter ($88). Individual variation of MRSA colonization rates over wide ranges (0% – 30%) had lesser effects on results.
Conclusions:
MRSA nares PCR use in hospitalized pediatric patients with CAP or tracheitis was generally favored when empiric MRSA empiric treatment rates are moderate or high.
This study evaluated Medicaid claims (MC) data as a valid source for outpatient antimicrobial stewardship programs (ASPs) by comparing it to electronic medical record (EMR) data from a single academic center.
Methods:
This retrospective study compared pediatric patients’ MC data with EMR data from the Marshall Health Network (MHN). Claims were matched to EMR records based on patient Medicaid ID, service date, and provider NPI number. Demographics, antibiotic choice, diagnosis appropriateness, and guideline concordance were assessed across both data sources.
Setting:
The study was conducted within the MHN, involving multiple pediatric and family medicine outpatient practices in West Virginia, USA.
Patients:
Pediatric patients receiving care within MHN with Medicaid coverage.
Results:
MC and EMR data showed >90% agreement in antibiotic choice, gender, and date of service. Discrepancies were observed in diagnoses, especially for visits with multiple infectious diagnoses. MC data demonstrated similar accuracy to EMR data in identifying inappropriate prescriptions and assessing guideline concordance. Additionally, MC data provided timely information, enhancing the feasibility of impactful outpatient ASP interventions.
Conclusion:
MC data is a valid and timely resource for outpatient ASP interventions. Insurance providers should be leveraged as key partners to support large-scale outpatient stewardship efforts.
Objectives/Goals: Cervical cancer is preventable through HPV vaccination and the detection/removal of precancerous lesions. Incidence and mortality rates have only decreased by 3–4% in the past decade. Despite having the tools to prevent all cervical cancers, they are not being fully utilized. Our goal is to identify barriers and design strategies to overcome them. Methods/Study Population: Women in urban (750) and rural (750) settings will be screened for the presence of high-oncogenic risk HPV (hrHPV) by self-vaginal swab, complete the Monitoring Blunting Style Scale, a validation scale to determine attentional style, and a structural barrier to care survey. A subset (Results/Anticipated Results: The study, launched in September 2024 at the Medicine Primary Care Clinic at UMC in New Orleans, has enrolled 16 women. Sample adequacy was high (82%), with 5 women having hrHPV present. Participants expressed high satisfaction and acceptance of the self-administered vaginal swab, with most samples demonstrating high quality. Surveys have been collected, and hrHPV-positive women have been referred for gynecological follow-up. Shreveport site will recruit women across over 20 rural clinical sites using a Mobile Health Unit to increase access in rural and underserved communities. Discussion/Significance of Impact: The baseline study will take 12–18 months. We will identify and address key barriers to follow-up gynecological care, including logistical issues (improving access and navigation), educational needs (developing culturally sensitive materials), and emotional support. We will create a care delivery model to eliminate cervical cancer in Louisiana.
The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) trial demonstrated that minimally invasive surgery to treat spontaneous lobar intracerebral hemorrhage (ICH) improved functional outcomes. We aimed to explore current management trends for spontaneous lobar ICH in Canada to assess practice patterns and determine whether further randomized controlled trials are needed to clarify the role of surgical intervention.
Methods:
Neurologists, neurosurgeons, physiatrists and trainees in these specialties were invited to complete a 16-question survey exploring three areas: (1) current management for spontaneous lobar ICH at their institution, (2) perceived influence of ENRICH on their practice and (3) perceived need for additional clinical trial data. Standard descriptive statistics were used to report categorical variables. The χ2 test was used to compare responses across specialties and career stages.
Results:
The survey was sent to 433 physicians, and 101 (23.3%) responded. Sixty-eight percent of participants reported that prior to publication of the ENRICH trial, spontaneous lobar ICH was primarily managed conservatively, with surgery reserved for life-threatening situations. Forty-three percent of participants did not foresee a significant increase in surgical intervention at their institution. Of neurosurgical respondents, 33% remained hesitant to offer surgical intervention beyond lifesaving operations. Only 5% reported routinely using specifically designed technologies to evacuate ICH. Seventy percent reported that another randomized controlled trial comparing nonsurgical to surgical management for spontaneous lobar ICH is needed.
Conclusions:
There is significant practice variability in the management of spontaneous lobar ICH across Canadian institutions, stressing the need for additional clinical trial data to determine the role of surgical intervention.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Operative cancellations adversely affect patient health and impose resource strain on the healthcare system. Here, our objective was to describe neurosurgical cancellations at five Canadian academic institutions.
Methods:
The Canadian Neurosurgery Research Collaborative performed a retrospective cohort study capturing neurosurgical procedure cancellation data at five Canadian academic centres, during the period between January 1, 2014 and December 31, 2018. Demographics, procedure type, reason for cancellation, admission status and case acuity were collected. Cancellation rates were compared on the basis of demographic data, procedural data and between centres.
Results:
Overall, 7,734 cancellations were captured across five sites. Mean age of the aggregate cohort was 57.1 ± 17.2 years. The overall procedure cancellation rate was 18.2%. The five-year neurosurgical operative cancellation rate differed between Centre 1 and 2 (Centre 1: 25.9%; Centre 2: 13.0%, p = 0.008). Female patients less frequently experienced procedural cancellation. Elective, outpatient and spine procedures were more often cancelled. Reasons for cancellation included surgeon-related factors (28.2%), cancellation for a higher acuity case (23.9%), patient condition (17.2%), other factors (17.0%), resource availability (7.0%), operating room running late (6.4%) and anaesthesia-related (0.3%). When clustered, the reason for cancellation was patient-related in 17.2%, staffing-related in 28.5% and operational or resource-related in 54.3% of cases.
Conclusions:
Neurosurgical operative cancellations were common and most often related to operational or resource-related factors. Elective, outpatient and spine procedures were more often cancelled. These findings highlight areas for optimizing efficiency and targeted quality improvement initiatives.
To examine the association of co-morbidity with home-time after acute stroke and whether the association is influenced by age.
Methods:
We conducted a province-wide study using linked administrative databases to identify all admissions for first acute ischemic stroke or intracerebral hemorrhage between 2007 and 2018 in Alberta, Canada. We used ischemic stroke-weighted Charlson Co-morbidity Index of 3 or more to identify those with severe co-morbidity. We used zero-inflated negative binomial models to determine the association of severe co-morbidity with 90-day and 1-year home-time, and logistic models for achieving ≥ 80 out of 90 days of home-time, assessing for effect modification by age and adjusting for sex, stroke type, comprehensive stroke center care, hypertension, atrial fibrillation, year of study, and separately adjusting for estimated stroke severity. We also evaluated individual co-morbidities.
Results:
Among 28,672 patients in our final cohort, severe co-morbidity was present in 27.7% and was associated with lower home-time, with a greater number of days lost at younger age (−13 days at age < 60 compared to −7 days at age 80+ years for 90-day home-time; −69 days at age < 60 compared to −51 days at age 80+ years for 1-year home-time). The reduction in probability of achieving ≥ 80 days of home-time was also greater at younger age (−22.7% at age < 60 years compared to −9.0% at age 80+ years). Results were attenuated but remained significant after adjusting for estimated stroke severity and excluding those who died. Myocardial infarction, diabetes, and cancer/metastases had a greater association with lower home-time at younger age, and those with dementia had the greatest reduction in home time.
Conclusion:
Severe co-morbidity in acute stroke is associated with lower home-time, more strongly at younger age.
We describe an analysis of the flaked stone tools recovered from households in the Postclassic central Mexican city of Calixtlahuaca (a.d. 1130–1530). Most artifacts are obsidian and represent the blade-core technology, but biface and bipolar artifacts are also represented. Even though household residents were involved in limited biface and bipolar reduction, it appears that the city did not have any resident blade producers. This finding is at odds with the views of many archaeologists, who tend to associate craft production with the emergence of complex Mesoamerican urban centers. We examine the technologies from temporally distinct Calixtlahuacan household assemblages. We discuss why the quantity and quality artifacts associated with blade production are not consistent with resident blade making in the city. Finally, we examine four models for blade provisioning: (1) whole-blade trade, (2) processed-blade trade, (3) long-distance itinerant craftsmen, and (4) local, hinterland-based craftsmen. Evaluating how the Calixtlahuacans got their flaked stone tools has important implications for the comparative understanding of the organization and scale of economic provisioning systems in Postclassic central Mexico. This analysis supports new inferences about the nature of commercial networks that supplied the Toluca Valley prior to the arrival of the Spanish in the sixteenth century.
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.
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.
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.
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.
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.