The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRFdependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction. Significance StatementThe dorsomedial PFC and its striatal targets play a critical role in higher cognitive function. PFC-dependent cognitive dysfunction is associated with many psychiatric disorders. Although it has long-been known that corticotropin-releasing factor (CRF) neurons are prominent within the PFC, their role in cognition has remained unclear. Using a novel chemogenetic viral vector system, the present studies demonstrate that PFC CRF neurons impair working memory via activation of local PKA-coupled CRF receptors, an action associated with robust degradation in task-related frontostriatal neuronal coding. Conversely, suppression of constitutive PFC CRF activity improved working memory. Collectively, these studies provide novel insight into the neurobiology of cognition and suggest that CRF may represent a novel target for the treatment of cognitive dysfunction.

Background Improving care transitions following emergency department (ED) visits may reduce post‐ED adverse events among older adults (e.g., ED revisits, decreased function). The Care Transitions Intervention (CTI) improves hospital‐to‐home transitions; however, its effectiveness at improving post‐ED outcomes is unknown. We tested the effectiveness of the CTI with community‐dwelling older adult ED patients, hypothesizing that it would reduce revisits and increase performance of self‐management behaviors during the 30 days following discharge. Methods We conducted a randomized controlled trial among patients age ≥ 60 discharged home from one of three EDs in two states. Intervention participants received a minimally modified CTI, with a home visit 24 to 72 h postdischarge and one to three phone calls over 28 days. We collected demographic, health status, and psychosocial data at the initial ED visit. Medication adherence and knowledge of red flag symptoms were assessed via phone survey. Care use and comorbidities were abstracted from medical records. We performed multivariate regressions for intention‐to‐treat and per‐protocol (PP) analyses. Results Participant characteristics (N = 1,756) were similar across groups: mean age 72.4 ± 8.6 years and 53% female. Of those randomized to the intervention, 84% completed the home visit. Overall, 12.4% of participants returned to the ED within 30 days. The CTI did not significantly affect odds of 30‐day ED revisits (adjusted odds ratio [AOR] = 0.97, 95% confidence interval [CI] = 0.72 to 1.30) or medication adherence (AOR = 0.89, 95% CI = 0.60 to 1.32). Participants receiving the CTI (PP) had increased odds of in‐person follow‐up with outpatient clinicians during the week following discharge (AOR = 1.24, 95% CI = 1.01 to 1.51) and recalling at least one red flag from ED discharge instructions (AOR = 1.34 95% CI = 1.05 to 1.71). Conclusions The CTI did not reduce 30‐day ED revisits but did significantly increase key care transition behaviors (outpatient follow‐up, red flag knowledge). Additional research is needed to explore if patients with different conditions benefit more from the CTI and whether decreasing ED revisits is the most appropriate outcome for all older adults.

Background Up to half of community‐dwelling older adults with impaired cognition who are discharged home from the emergency department (ED) return for further care within 30 days. We examined the effects of delivering the Care Transitions Intervention (CTI) to older adult patients with impaired cognition discharged home from the ED, hypothesizing that the CTI would decrease ED revisits in the following 30 days. Method We conducted a pre‐planned sub‐analysis of community‐dwelling older adults (age≥60 years) with impaired cognition participating in a single‐blind, randomized controlled trial testing the effectiveness of the CTI adapted for use following ED discharge. The parent study recruited ED patients from three university‐affiliated hospitals from 2016–2019. Subjects eligible for this analysis had to: 1) have a primary care provider within these health systems; 2) be discharged to a community residence; 3) not receive care management or hospice services; and 4) be cognitively impaired in the ED, as determined by a score>10 on the Blessed Orientation Memory Concentration Test. Intervention group subjects received a home visit from a trained paramedic coach within 72 hours of discharge, and up to three follow‐up phone calls during the following month. Our primary outcome was occurrence of any ED revisit within 30 days of discharge. Secondary outcomes included any ED revisit within 14 days and outpatient clinic follow‐up. We evaluated intervention effects using multivariate logistic regression. Result Of our sub‐sample (N=81, 36 control, 45 treatment), 57% were female and the mean age was 78 years. Bivariate comparison of primary and secondary outcomes found no significant differences. Multivariate analysis, adjusted for the presence of moderate to severe depression and inadequate health literacy, found that the CTI significantly reduced the odds of a repeat ED visit within 30 days (OR 0.25, 95%CI 0.07‐0.90) but not 14 days (OR 1.01, 95%CI 0.26‐3.93). Multivariate analysis of outpatient follow‐up found no significant effects. Conclusion Community‐dwelling older adults with cognitive impairment receiving the CTI following ED discharge experienced fewer ED revisits within 30 days compared to usual care. Further studies must confirm and expand upon this finding, identifying features with greatest benefit to patients and caregivers.

Objective Older adults discharged from the emergency department (ED) are at high risk for adverse outcomes. Adherence to ED discharge instructions is necessary to reduce those risks. The objective of this study is to determine the individual‐level factors associated with adherence with ED discharge instructions among older adult ED outpatients. Methods We performed a secondary analysis of data from the control group of a randomized controlled trial testing a care transitions intervention among older adults (age ≥ 60 years) discharged home from the ED in two states. Taking data from patient surveys and chart reviews, we used multivariable logistic regression to identify patient characteristics associated with adherence to printed discharge instructions. Outcomes were patient‐reported medication adherence, provider follow‐up visit adherence, and knowledge of “red flags” (signs of worsening health requiring further medical attention). Results A total 824 patients were potentially eligible, and 699 had data in at least one pillar. A total of 35% adhered to medication instructions, 76% adhered to follow‐up instructions, and 35% recalled at least one red flag. In the multivariate analysis, no factors were significantly associated with failure to adhere to medications. Participants with poor health status (adjusted odds ratio [AOR] = 0.55, 95% confidence interval [CI] = 0.31 to 0.98) were less likely to adhere to follow‐up instructions. Participants who were older (AORs trended downward as age category increased) or depressed (AOR = 0.39, 95% CI = 0.17 to 0.85) or had one or more functional limitations (AOR = 0.62, 95% CI = 0.41 to 0.94) were less likely to recall red flags. Conclusion Older adults discharged home from the ED have mixed rates of adherence to discharge instructions. Although it is thought that some subgroups may be higher risk than others, given the opportunity to improve ED‐to‐home transitions, EDs and health systems should consider providing additional care transition support to all older adults discharged home from the ED.

Background/objectives: Despite a high prevalence and association with poor outcomes, screening to identify cognitive impairment (CI) in the emergency department (ED) is uncommon. Identification of high-risk subsets of older adults is a critical challenge to expanding screening programs. We developed and evaluated an automated screening tool to identify a subset of patients at high risk for CI. Methods:In this secondary analysis of existing data collected for a randomized control trial, we developed machine-learning models to identify patients at higher risk of CI using only variables available in electronic health record (EHR). We used records from 1736 community-dwelling adults age > 59 being discharged from three EDs. Potential CI was determined based on the Blessed Orientation Memory Concentration (BOMC) test, administered in the ED. A nested cross-validation framework was used to evaluate machine-learning algorithms, comparing area under the receiver-operator curve (AUC) as the primary metric of performance.Results: Based on BOMC scores, 121 of 1736 (7%) participants screened positive for potential CI at the time of their ED visit. The best performing algorithm, an XGBoost model, predicted BOMC positivity with an AUC of 0.72. With a classification threshold of 0.4, this model had a sensitivity of 0.73, a specificity of 0.64, a negative predictive value of 0.97, and a positive predictive value of 0.13. In a hypothetical ED with 200 older adult visits per week, the use of this model would lead to a decrease in the in-person screening burden from 200 to 77 individuals in order to detect 10 of 14 patients who would fail a BOMC. Conclusion:This study demonstrates that an algorithm based on EHR data can define a subset of patients at higher risk for CI. Incorporating such an See related editorial by Hirshon in this issue.