Faculty Bibliography

UNLABELLED:Social-emotional competence is critical to children's social and school success, prompting interest in understanding factors that promote these skills prior to elementary-school. Cognitive stimulation (e.g., reading, playing) is related to preschool children's social outcomes; However, few studies have examined these associations earlier, or determined whether interventions that encourage cognitive stimulation may enhance children's early social-emotional competencies either directly, or through impact on these behaviors. The present study examined whether cognitive stimulation in infancy predicted social competence in toddlerhood and the impact of a positive parenting intervention on these child outcomes. Mother-infant dyads in the Smart Beginnings (SB) RCT (primarily Hispanic/Latino or Black and from low-income backgrounds) were randomly assigned to treatment or control. SB integrates universal primary prevention in pediatric primary care (PlayReadVIP); and targeted/secondary prevention through home visiting (Family Check-Up). Mothers' cognitive stimulation at 6 months significantly predicted children's social-emotional competence at 24 months. Although there was no direct effect of SB on children's social-emotional competence, there was an indirect effect on children's social competence through maternal cognitive stimulation. Findings suggest that associations between cognitive stimulation and children's social-emotional competence emerge earlier than previously shown, and that positive parenting interventions can support early social-emotional competence through impact on cognitive stimulation. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov identifier: NCT02459327.

OBJECTIVE:Personalized approaches to ischemic stroke diagnosis are needed. We determine differences in proteomic signatures of incident embolic (EIS) and thrombotic stroke (TIS) by age and resultant pathways using large-scale proteomics. METHODS:Participants in the Atherosclerosis Risk in Communities Study (ARIC) from visit 2 (V2, 1990-1992) until 2020 without prevalent stroke with available SomaScan data (4,955 protein targets) at V2 (mid-life, n = 10,929), and then again at visit 5 (V5, 2011-2013, n = 4,463) were included. Covariate adjusted Cox hazard models determined the association between proteins, and adjudicated incident EIS or TIS from V2 to V5 and from V5 to 2020. RESULTS:Among 10,929 participants (56% female, 23% Black, follow-up ~20 years), 20 proteins measured in mid-life were associated with either EIS (n = 168) or TIS (n = 459) in mid-life, and 4 measured in late-life were associated with late-life stroke (73 EIS and 124 TIS events) at the Bonferroni threshold p < 1E-5. In mid-life, N-terminal pro-B-type natriuretic peptide (NPPB) was significantly associated with EIS, but not TIS (p-difference = 9.14E-7). Nineteen mid-life proteins were strongly associated with TIS; 7 strongly associated with TIS and only nominally (p < 0.05) with EIS and the remaining 12 with TIS only. In late-life, NPPB, serine protease inhibitor Kazal-type 4, oligodendrocyte-myelin-glycoprotein, and neurocan-core protein were significantly associated with EIS, but not TIS. Ingenuity Pathway Analysis tools implicated cancer for EIS-associated proteins, whereas TIS pathways reflected cell-structure and atherogenesis. INTERPRETATION/CONCLUSIONS:We identified plasma proteins associated with risk of EIS versus TIS reflecting distinct stroke mechanisms: cardiac dysfunction protein in EIS (eg, NPPB) and inflammation dysregulation in TIS (eg, interleukins). ANN NEUROL 2025.

BACKGROUND:on dementia may be more severe in this population. METHODS:and dementia risk factors using a Wald test. Models were adjusted for confounders, including social determinants of health. RESULTS:was associated with 1.90-fold higher odds of global cognitive impairment (95% CI: 1.48-2.46), and 3.29-fold higher risk of dementia (95% CI: 1.14-9.55). CONCLUSION/CONCLUSIONS:neighborhoods should discuss cognitive assessments and ways to increase physical activity with providers.

AIMS/OBJECTIVE:To evaluate a previously proposed type 2 diabetes staging schema by examining the decline in oral beta-cell compensation and the increase in diabetes risk. METHODS:We analyzed 1,235 participants (43-85 years) from one ELSA-Brasil center. We defined stages as previously proposed: stage 1, isolated 1-h PG ≥155 mg/dL; stage 2, also having prediabetes/intermediate hyperglycemia (preDM/IH) defined by the American Diabetes Association (ADA); and stage 3, diabetes. We made additional evaluations defining IH based on the World Health Organization (WHO)/International Expert Committee (IEC) criteria. We estimated beta-cell compensation with the insulin secretion-sensitivity index-2 (ISSI-2). RESULTS:ISSI-2 declined (p < 0.001) across stages. After 5.29 (0.44) years (n = 850), the adjusted diabetes incidence increased from stage 0 (normoglycemia) to stage 1 (RR = 2.64;1.12,6.22) and stage 2 (RR = 5.94;2.83,12.44), considering WHO/IEC criteria. With the ADA criteria, RRs were larger but not progressive. Adding 1-h PG testing doubled the detection of unknown diabetes. A strategy combining FPG with 1-h PG performed just as well as using all four tests. CONCLUSIONS:Staging captured progressive deterioration to type 2 diabetes. Adding 1-h PG improved current and future case detection, which represents a major advance in diabetes prevention. However, refinements in staging will require further evaluation of tests and their thresholds.

BACKGROUND:We previously reported that individuals with the Transient receptor potential melastatin 7 (TRPM7) GA/AA genotype and consumed diets high in Ca:Mg ratio had an increased risk of colorectal polyps. OBJECTIVE:The aim was to identify if the gut microbiota plays a role in the association of TRPM7 genotype, Ca:Mg intake ratio and risk of colorectal polyps. METHODS:We analyzed the gut microbiota of 240 participants in a double-blind 2x2 factorial (TRPM7 genotype and Ca:Mg intake ratios) randomized trial by sequencing the stool, rectal swab, and rectal mucosa tissue samples of each participant. RESULTS:The gut microbiota of participants with the GA genotype significantly differed from those with the GG genotype in all three sample types, with an altered abundance of Prevotella and Bacteroides in swab samples. Prevotella in rectal mucosa and Bacteroides in swab were associated with an increased risk of metachronous colorectal polyps. Optimizing high diet Ca:Mg ratios to 2.3 through Mg supplementation resulted in a reduced abundance of Prevotella in rectal swabs and Bacteroides in stool samples. We identified multiple microbes in all three sample types linked to the risk of metachronous colorectal polyps. CONCLUSIONS:Our findings indicate that the gut microbiota in stool, rectal swab and mucosa are associated with the risk of metachronous colorectal polyps, and diet changes could modify the abundance of TRPM7-related microbes. CLINICAL TRIAL REGISTRATION/BACKGROUND:The study was registered as NCT01105169 at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT01105169.

INTRODUCTION/BACKGROUND:Sleep disturbances are common in older people with cognitive impairment, potentially contributing to negative outcomes. A core outcome set (COS) is required to reduce heterogeneity in clinical trials and promote the development of high-quality evidence to support clinical management. METHODS:A multi-stage mixed methods study was conducted in accordance with The Core Outcome Set Standards for Development. RESULTS:A systematic review identified 287 sleep outcomes from previous clinical trials. Qualitative interviews ensured the COS was informed by what matters most to people with cognitive impairment and their caregivers. A modified Delphi process identified nine outcomes for the COS: total sleep time, sleep onset latency, wakefulness after sleep onset, number of night-time awakenings, sleep efficiency, and measures of sleep quality, daytime sleepiness, cognition, and mood. DISCUSSION/CONCLUSIONS:This COS will support researchers to produce more reliable and coherent trial data to guide the management of sleep disturbances in people with neurodegenerative cognitive impairment. HIGHLIGHTS/CONCLUSIONS:Evidence is lacking regarding the treatment of sleep disturbances in people with cognitive impairment. Heterogeneity of reported outcomes in clinical trials limits data synthesis. A qualitative analysis established what matters most to people with cognitive impairment and their caregivers when determining treatment effectiveness. A Delphi panel of experts agreed upon a core outcome set. This core outcome set will improve the reliability and comparability of data from future trials.

Parental reflective functioning (PRF) refers to a parent's ability to understand their own and their child's mental states and connect them to behaviors. This longitudinal study evaluated (1) associations among prenatal PRF, using the Pregnancy Interview, demographics, prenatal maternal depressive symptoms, and maternal-fetal attachment and (2) whether prenatal PRF predicted parenting quality assessed during unstructured and challenging mother-child interaction tasks beyond infancy, after controlling for cumulative risk. Data were collected in an urban community sample of women in the midwestern US. Prenatal PRF was positively associated with maternal educational attainment and negatively associated with cumulative demographic risk, but not with depressive symptoms or maternal-fetal attachment. Controlling for cumulative risk, hierarchical regressions showed that prenatal PRF was the sole significant predictor of positive parenting at 36 months, observed during a challenging teaching task but not during free play. Prenatal PRF did not predict negative parenting. These patterns persisted when analyses were repeated within a subsample of Black mothers, with PRF again being the sole significant predictor of positive parenting. Further attention to cultural variations in PRF and parenting in future research is warranted.

INTRODUCTION/BACKGROUND:The Neighborhoods Study (TNS) is a novel investigation of adverse social exposome and brain health leveraging 22 Alzheimer's Disease Research Centers (ADRCs). TNS aims to understand if the adverse social exposures increase Alzheimer's disease and related dementias (ADRD) risk. METHODS:TNS uses innovative methods to determine lifetime addresses of living (n = ≈ 3116) and brain bank cohorts (n = ≈ 8637). Addresses are linked to time-concordant adverse social exposome using the Area Deprivation Index (ADI) and summarized over time. Brain health measures are provided by the National Alzheimer's Coordinating Center. RESULTS:We highlight a general overview and methodology of TNS. Data collection is ongoing; however, preliminary findings indicate that the adverse social exposome is related to ADRD biomarkers, neuropathology, and cognitive function. DISCUSSION/CONCLUSIONS:TNS is the largest study of adverse social exposome and ADRD, using the ADRC network to build robust scientific consortia. Its findings will inform ADRD interventions, precision medicine, and policy. HIGHLIGHTS/CONCLUSIONS:The Neighborhoods Study (TNS) investigates adverse social exposome and brain health. TNS is a collaboration among 22 Alzheimer's Disease Research Centers. TNS will give insight on environmental and exposomal factors which may be modifiable. Participant lifetime addresses are linked to temporal adverse social exposome metrics. This study's findings will inform precision approaches to mitigate dementia risk.

RATIONALE/BACKGROUND:Abrupt air quality improvements have followed the closure or dramatic emission control of large air pollution sources. These "natural experiments" provide ideal opportunities to assess the real-world health benefits of air quality improvements. The shutdown of the Shenango coking plant, a significant fossil-fuel pollution source located on an island in the Ohio River near Pittsburgh, PA, presented such an opportunity to test for changes in respiratory health in the local community following the closure. OBJECTIVES/OBJECTIVE:To identify and quantify the immediate and/or longer-term changes in respiratory hospitalizations and emergency department (ED) visits among the population residing near the Shenango coke plant at the time of its closure. METHODS:We acquired data for respiratory hospitalizations and ED visit counts by residents living in zip codes surrounding the plant, as well as at comparison control sites, three years before and after the shutdown date. The immediate and longer-term changes of respiratory health outcomes were tested with an interrupted time series model, and compared with external control sites and internal control outcomes. MEASUREMENTS AND MAIN RESULTS/RESULTS:We found the closure of the Shenango plant was associated with an immediate 20.5% (95% CI: 12.8%-27.6%) decrease for weekly respiratory ED visits, and an immediate 41.2% (95% CI: 14.4%-59.9%) decrease in pediatric asthma ED visits, followed by an additional 4% per month longer-term downward trend. Longer-term reductions, as compared to pre-closure trends, were also observed for chronic obstructive pulmonary disease hospitalizations. CONCLUSIONS:Our study provides strong confirmation that reductions in fossil-fuel-related air pollution produce both short and longer-term respiratory health benefits. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).