The association between pulse pressure change and cognition in late life: Age and where you start matters

AbstractIntroductionVariations across studies in the association between blood pressure (BP) and cognition might be explained partly by duration of exposure to hypertension and partly by nonrandom attrition over time. Pulse pressure (PP) reflects arterial stiffness which may better reflect chronicity of hypertension.MethodsOver six annual cycles, 1954 individuals aged 65+ years from a prospective population-based cohort underwent BP measurements and cognitive evaluations. We examined the relationship of change in five cognitive domains to longitudinal PP patterns across the late-life age spectrum, before and after stratifying by baseline systolic blood pressure (SBP) and adjusting for attrition.ResultsThere were four longitudinal PP patterns: stable normal, stable high, increasing, and decreasing. Those with lower baseline SBP and an increasing or stable high PP had less decline in cognition, an effect that was attenuated with aging. Among those with higher baseline SBP, there were no differences across PP groups, but increasing age was consistently associated with greater cognitive decline.DiscussionThe effect of PP on cognitive decline depends on age, baseline SBP, and the trajectory of PP change. Cardiovascular mechanisms underlying cognitive aging should be recognized as nuanced and dynamic processes when exploring prevention and treatment targets in the elderly, so that the optimal timing and type of intervention can be identified

Trials and Tribulations of Humanizing Mice for Cancer Research

Cancers are aggressive, evasive, and ruthless killers, claiming millions of lives every year. Cancers are heterogeneous and there is often no single, clearly defined problem as they harness and manipulate a multitude of fundamental mechanisms at the very essence of life. To investigate these mechanisms and vet potential interventive therapies, humanized mice offer a unique model as a prelude to the use of nanosecond pulse stimulation (NPS), a pulse power technology applying nanosecond duration, high electric field pulses, to ablate human tumors. Immunodeficient mouse strains, NSG and NSG-SGM3, were engrafted with human immune cells and human tumors, which would allow us to study the effects of NPS therapy on the human tumor and the human immune system, albeit not without trials and tribulations. Here we show that mice engrafted with human cord blood CD34+ hematopoietic stem cells (hCD34+ HSC) lack consistency in expansion and chimerism, or variety of immune cell types. Unfortunately, mice that developed the human immune system rejected the human tumors without treatment, while mice that rejected the immune system developed the human tumors. Therefore, we had mice with human immune systems and no tumor to treat, and mice with tumors to treat yet no immune system to study. In non-humanized mice, NPS induced complete tumor death in the patient derived mammary cancer xenograft (PDX) model, but not in the MDA-MB-231 VIM-RFP mammary cancer cell-derived xenograft (CDX) model. The absence of NPS elimination of the CDX is the only known NPS cancer failure and requires further study.https://digitalcommons.odu.edu/gradposters2021_gradschool/1000/thumbnail.jp

Cardiovascular fitness associated with cognitive performance in heart failure patients enrolled in cardiac rehabilitation

Abstract Background Reduced cognitive function is common in persons with heart failure (HF). Cardiovascular fitness is a known contributor to cognitive function in many patient populations, but has only been linked to cognition based on estimates of fitness in HF. The current study examined the relationship between fitness as measured by metabolic equivalents (METs) from a standardized stress test and cognition in persons with HF, as well as the validity of office-based predictors of fitness in this population. Methods Forty-one HF patients enrolled in cardiac rehabilitation completed a standardized exercise stress test protocol, a brief neuropsychological battery, the 2-minute step test (2MST), and a series of medical history and self-report questionnaires. Results Maximum METs from stress testing demonstrated incremental predictive validity for attention (β = .41,p = .03), executive function (β = .37,p = .04), and memory domains (β = .46,p = .04). Partial correlations accounting for key medical and demographic characteristics revealed greater METs was associated with the 2MST (r(32) = .41,p = .02) but not with the Duke Activity Status Index (DASI) (r(32) = .24,p = .17). Conclusion The current findings indicate that better fitness levels measured by METs is independently associated with better cognitive function in older adults with HF. Results also showed that METs was closely associated with one office-based measure of fitness (2MST), but not another (DASI). Prospective studies are needed to clarify the mechanisms linking fitness and cognitive function in HF

Sleep Apnea and Cognitive Function in Heart Failure

Background. Prior research indicates that heart failure (HF) patients exhibit significant cognitive deficits on neuropsychological testing. Sleep apnea is associated with both HF and reduced cognitive function, but the combined impact of these conditions on cognitive function is unknown. Methods. In the current study, 172 older adults with a dual diagnosis of HF and sleep apnea or HF alone completed a battery of cognitive tests measuring attention, executive functioning, and memory. Results. Relative to patients with HF alone, persons with both HF and sleep apnea performed worse on measures of attention after adjusting for demographic and medical variables. Conclusions. The current findings suggest that HF patients with comorbid sleep apnea may be at greater risk for cognitive impairment relative to HF patient without such history. Further work is needed to clarify mechanisms for these findings and to determine whether the interactive effects on cognitive function lead to poorer patient outcomes

The Additive Effects of Type-2 Diabetes on Cognitive Function in Older Adults with Heart Failure

Background. Medical comorbidity has been theorized to contribute to cognitive impairment in heart failure (HF) patients. Specifically, type-2 diabetes mellitus (T2DM), a common coexisting condition among HF patients, may be an independent predictor of cognitive impairment. Nonetheless, the relationships between T2DM and other risk factors for cognitive impairment among persons with HF are unclear. Methods. Persons with HF (N = 169, 34.3% women, age 68.57 ± 10.28 years) completed neuropsychological testing within a framework of an ongoing study. History of T2DM, along with other medical characteristics, was ascertained through a review of participants' medical charts and self-report. Results. Many participants (34.9%) had a comorbid T2DM diagnosis. After adjustment for demographic and medical characteristics, HF patients with T2DM evidenced significantly greater impairments across multiple cognitive domains than HF patients without T2DM: λ = .92, F(5, 156) = 2.82, P = .018. Post hoc tests revealed significant associations between T2DM and attention (P = .003), executive function (P = .032), and motor functioning (P = .008). Conclusion. The findings suggest additive contributions of T2DM and HF to impairments in attention, executive function, and motor function. Future work is needed to elucidate the mechanisms by which T2DM exacerbates cognitive impairment in HF

Validation of the Persistent Complex Bereavement Disorder (PCBD) Checklist: A Developmentally Informed Assessment Tool for Bereaved Youth

The inclusion of Persistent Complex Bereavement Disorder (PCBD) in the DSMâ 5 appendix signifies a call for research regarding the distinguishing features and clinical utility of proposed PCBD criteria. Rigorously constructed tools for assessing PCBD are lacking, especially for youth. This study evaluated the validity and clinical utility of the PCBD Checklist, a 39â item measure designed to assess PCBD criteria in youth aged 8 to18 years. Test construction procedures involved: (a) reviewing the literature regarding developmental manifestations of proposed criteria, (b) creating a developmentally informed item pool, (c) surveying an expert panel to evaluate the clarity and developmental appropriateness of candidate items, (d) conducting focus groups to evaluate the comprehensibility and acceptability of items, and (e) evaluating psychometric properties in 367 bereaved youth (Mage = 13.49, 55.0% female). The panel, clinicians, and youth provided favorable content validity and comprehensibility ratings for candidate items. As hypothesized, youth who met full PCBD criteria, Criterion B (e.g., preoccupation with the deceased and/or circumstances of the death), or Criterion C (e.g., reactive distress and/or social/identity disruption) reported higher posttraumatic stress and depressive symptoms than youth who did not meet these criteria, ηp2 = .07â .16. Youth who met Criterion C reported greater functional impairment than youth who did not, ηp2 = .08â .12. Youth who qualified for the â traumatic bereavement specifierâ reported more frequent posttraumatic stress symptoms than youth who did not, ηp2 = .04. Findings support the convergent, discriminant, and discriminantâ groups validity, developmental appropriateness, and clinical utility of the PCBD Checklist.ResumenValidación de Lista de verificación del Trastorno por Duelo Complejo Persistente (TDCP): Un informe del desarrollo de herramientas de medición para duelo en jóvenesLISTA DE CHEQUEO DE TRASTORNO DE DUELO COMPLEJO PERSISTENTELa inclusión del trastorno de duelo complejo persistente (TDCP en su sigla en español; PCBD en sus siglas en inglés) en el apéndice del DSMâ 5 significa un llamado para investigar en relación a las características distintivas y la utilidad clínica de los criterios propuestos para el TDCP. Se carece de herramientas rigurosamente construidas para evaluar TDCP, especialmente para jóvenes. Este estudio evalúa la validez y utilidad clínica de la lista de verificación de TPCP, una medida con 39 ítems diseñada para medir el criterio de TDCP en jóvenes de edades entre 8 a 18 años. El procedimiento de construcción del test involucró: (a) revisión de la literatura relacionada con manifestaciones desarrolladas del criterio propuesto; (b) creación de un pool de ítems informados para el desarrollo; (c) encuesta a un panel experto para evaluar la claridad y desarrollo apropiado de los ítems; (d) conducir grupos focales para evaluar la compresibilidad y aceptabilidad de los ítems; y (e) evaluación de propiedades psicométricas en 367 jóvenes en proceso de duelo (M edad = 13.49, 55.0% femenino). El panel, los clínicos y los jóvenes en proceso de duelo proveyeron una validez de contenido favorable y rangos de comprensibilidad para los ítems candidatos. Como se hipotetizó, los jóvenes que cumplieron el criterio completo de TDCP, criterio B (ej., preocupación por el fallecido y/o las circunstancias de la muerte) o el criterio C (ej., estrés reactivo y/o perturbación social/identidad) reportaron alto estrés postraumático y síntomas depresivos que los jóvenes que no cumplen este criterio, ηp2 = .07 a .16. Los jóvenes que no cumplieron el criterio C reportaron mayor deterioro funcional que los jóvenes que no lo cumplieron ηp2 = .08 a .12. Los jóvenes que calificaron para el â duelo traumático especificoâ reportaron mayor frecuencia de síntomas de estrés postraumático que jóvenes que no calificaron ηp2 = .04. 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Recital Program

Recital program for students of Lexie Hansen, Haley Bradshaw, Eliza Nelson, Kylee Paul, Mark Gubler, Lauren Malouf, Holly Ganoe, and Janessa LeMmon.https://digitalcommons.usu.edu/music_programs/1106/thumbnail.jp

Investigation of NRXN1 deletions: Clinical and molecular characterization

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P  = 6.08 × 10 −7 ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97220/1/35780_ftp.pd