A Scoping Review of Neighborhoods and Cognitive Health Disparities Among US Midlife and Older Adults.

Objectives: The neighborhood environment may be an important determinant of racial/ethnic disparities in cognitive function. To understand how neighborhoods are linked to cognition across racial/ethnic groups, this scoping review organizes research investigating relationships between multiple neighborhood domains and cognitive function in diverse samples of US midlife and older adults. Methods: PubMed/MEDLINE, Web of Science, and CAHL were used to extract quantitative disparities-focused studies (n = 17) that included US adults ages 50+, racial/ethnic minoritized populations, cognitive dependent variable(s), and neighborhood-level independent variable(s) published from January 2010 to October 2021. Results: Studies demonstrate variation within and between racial/ethnic groups in how neighborhood factors are associated with cognition. Economically and socially advantaged neighborhoods were associated with better cognition. Findings were mixed for built and neighborhood composition measures. Discussion: More research with greater racial/ethnic representation is needed to disentangle which aspects of the neighborhood are most salient for specific cognitive function domains across diverse populations.

Neuropsychiatric Symptoms and In Vivo Alzheimer's Biomarkers in Mild Cognitive Impairment.

BACKGROUND: Neuropsychiatric symptoms (NPS) carry an increased risk of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). There is a need to understand how to integrate NPS into the paradigm outlined in the 2018 NIA-AA Research Framework. OBJECTIVE: To evaluate a prediction model of MCI-AD progression using a collection of variables, including NPS, cognitive testing, apolipoprotein E4 status (APOE4), imaging and laboratory AD biomarkers. METHODS: Of 300 elderly subjects, 219 had stable MCI and 81 MCI-AD progression over a 5-year follow-up. NPS were measured using the Neuropsychiatric Inventory (NPI). A multivariate Cox Proportional Hazards Regression Analysis assessed the effects of APOE4, baseline NPI, baseline CSF amyloid-ß, phosphorylated and total tau, baseline AD-signature MRI biomarker, baseline memory and executive function on MCI-AD progression. RESULTS: 27% progressed to dementia (median follow-up = 43 months). NPS were found in stable MCI (62.6%) and MCI-AD converters (70.3%). The Cox model exhibited a good fit (p < 0.001), and NPS (HR = 1.033, p = 0.027), phosphorylated tau (HR = 1.011, p = 0.025), total tau (HR = 1.005, p = 0.024), AD-signature MRI biomarker (HR = 0.111, p = 0.002), executive function (HR = 0.727, p = 0.045), and memory performance (HR = 0.387, p < 0.001) were significantly associated with dementia. CONCLUSIONS: NPS may inform dementia risk assessment in conjunction with cognitive testing and imaging and laboratory AD biomarkers. NPS is independently associated with the risk of MCI-dementia progression, over and beyond the contributions of CSF biomarkers.

Impact of Artificial Intelligence Assistance on Chest CT Interpretation Times: A Prospective Randomized Study.

BACKGROUND. Deep learning-based convolutional neural networks have enabled major advances in development of artificial intelligence (AI) software applications. Modern AI applications offer comprehensive multiorgan evaluation. OBJECTIVE. The purpose of this article was to evaluate the impact of an automated AI platform integrated into clinical workflow for chest CT interpretation on radiologists' interpretation times when evaluated in a real-world clinical setting. METHODS. In this prospective single-center study, a commercial AI software solution was integrated into clinical workflow for chest CT interpretation. The software provided automated analysis of cardiac, pulmonary, and musculoskeletal findings, including labeling, segmenting, and measuring normal structures as well as detecting, labeling, and measuring abnormalities. AI-annotated images and autogenerated summary results were stored in the PACS and available to interpreting radiologists. A total of 390 patients (204 women, 186 men; mean age, 62.8 ± 13.3 [SD] years) who underwent out-patient chest CT between January 19, 2021, and January 28, 2021, were included. Scans were randomized using 1:1 allocation between AI-assisted and non-AI-assisted arms and were clinically interpreted by one of three cardiothoracic radiologists (65 scans per arm per radiologist; total of 195 scans per arm) who recorded interpretation times using a stopwatch. Findings were categorized according to review of report impressions. Interpretation times were compared between arms. RESULTS. Mean interpretation times were significantly shorter in the AI-assisted than in the non-AI-assisted arm for all three readers (289 ± 89 vs 344 ± 129 seconds, p < .001; 449 ± 110 vs 649 ± 82 seconds, p < .001; 281 ± 114 vs 348 ± 93 seconds, p = .01) and for readers combined (328 ± 122 vs 421 ± 175 seconds, p < .001). For readers combined, the mean difference was 93 seconds (95% CI, 63-123 seconds), corresponding with a 22.1% reduction in the AI-assisted arm. Mean interpretation time was also shorter in the AI-assisted arm compared with the non-AI-assisted arm for contrast-enhanced scans (83 seconds), noncontrast scans (104 seconds), negative scans (84 seconds), positive scans without significant new findings (117 seconds), and positive scans with significant new findings (92 seconds). CONCLUSION. Cardiothoracic radiologists exhibited a 22.1% reduction in chest CT interpretations times when they had access to results from an automated AI support platform during real-world clinical practice. CLINICAL IMPACT. Integration of the AI support platform into clinical workflow improved radiologist efficiency.

Additive value of epicardial adipose tissue quantification to coronary CT angiography-derived plaque characterization and CT fractional flow reserve for the prediction of lesion-specific ischemia.

OBJECTIVES: Epicardial adipose tissue (EAT) from coronary CT angiography (CCTA) is strongly associated with coronary artery disease (CAD). We investigated the additive value of EAT volume to coronary plaque quantification and CT-derived fractional flow reserve (CT-FFR) to predict lesion-specific ischemia. METHODS: Patients (n = 128, 60.6 ± 10.5 years, 61% male) with suspected CAD who had undergone invasive coronary angiography (ICA) and CCTA were retrospectively analyzed. EAT volume and plaque measures were derived from CCTA using a semi-automatic software approach, while CT-FFR was calculated using a machine learning algorithm. The predictive value and discriminatory power of EAT volume, plaque measures, and CT-FFR to identify ischemic CAD were assessed using invasive FFR as the reference standard. RESULTS: Fifty-five of 152 lesions showed ischemic CAD by invasive FFR. EAT volume, CCTA ≥ 50% stenosis, and CT-FFR were significantly different in lesions with and without hemodynamic significance (all p < 0.05). Multivariate analysis revealed predictive value for lesion-specific ischemia of these parameters: EAT volume (OR 2.93, p = 0.021), CCTA ≥ 50% (OR 4.56, p = 0.002), and CT-FFR (OR 6.74, p < 0.001). ROC analysis demonstrated incremental discriminatory value with the addition of EAT volume to plaque measures alone (AUC 0.84 vs. 0.62, p < 0.05). CT-FFR (AUC 0.89) showed slightly superior performance over EAT volume with plaque measures (AUC 0.84), however without significant difference (p > 0.05). CONCLUSIONS: EAT volume is significantly associated with ischemic CAD. The combination of EAT volume with plaque quantification demonstrates a predictive value for lesion-specific ischemia similar to that of CT-FFR. Thus, EAT may aid in the identification of hemodynamically significant coronary stenosis. KEY POINTS: • CT-derived EAT volume quantification demonstrates high discriminatory power to identify lesion-specific ischemia. • EAT volume shows incremental diagnostic performance over CCTA-derived plaque measures in detecting lesion-specific ischemia. • A combination of plaque measures with EAT volume provides a similar discriminatory value for detecting lesion-specific ischemia compared to CT-FFR.

Perceived Neighborhood Characteristics and Cognitive Functioning among Diverse Older Adults: An Intersectional Approach.

Unfavorable neighborhood conditions are linked to health disparities. Yet, a dearth of literature examines how neighborhood characteristics contribute to cognitive health in diverse samples of older adults. The present study uses an intersectional approach to examine how race/ethnicity, gender, and education moderate the association between neighborhood perceptions and cognitive functioning in later life. We used data from adults ≥65 years old (n = 8023) in the 2010-2016 waves of the nationally representative Health and Retirement Study (HRS). We conducted race/ethnicity-stratified linear regression models where cognitive functioning, measured using the 35-point Telephone Interview Cognitive Screen (TICS), was regressed on three neighborhood characteristics-cleanliness, safety, and social cohesion. We examine whether there is heterogeneity within race/ethnicity by testing if and how the relationship between neighborhood characteristics and cognitive functioning differs by gender and education. Among White adults, worse neighborhood characteristics were associated with lower cognitive functioning among those with less education. However, for Black adults, poor perceived quality of one's neighborhood was associated with worse cognitive functioning among those with more years of education compared to those with fewer years of education. Among Mexicans, perceived neighborhood uncleanliness was associated with lower cognitive functioning among those with less education, but higher cognitive functioning for those with higher levels of education. Thus, this study contributes to the literature on racial/ethnic disparities in cognitive aging disparities by examining neighborhood contextual factors as determinants of cognitive functioning. In particular, we find that higher education in the context of less favorable neighborhood environments does not confer the same benefits to cognitive functioning among all older adults.

Evaluating dysfunction in cognition and reward among offenders with antisocial personality disorder.

Antisocial personality disorder (APD) is a costly clinical condition. Previous studies identify executive dysfunction and reward sensitivity as factors contributing to APD. However, empirical evidence supporting the role of these factors in APD is mixed. The present study aimed to identify and specify APD-related dysfunction in cognitive and reward factors. In a sample of incarcerated males (N = 116), we administered three tasks targeting distinct cognitive (perception, executive functioning, and probabilistic decision-making) and reward (magnitude and consciousness) factors. APD was associated with impaired perception when high magnitude rewards were at stake, regardless of reward consciousness. APD was associated with worse executive functioning during conscious high rewards, as well as worse inhibition during high rewards when working memory demands were high. There was no APD-related performance difference during probabilistic decision-making. These findings expose the multifaceted nature of cognitive-affective dysfunction in APD, highlighting the importance of systematic research and providing insight into treatment targets. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Alternate versions of a fixed-choice, delay-discounting assessment for repeated-measures designs.

Delay discounting, reflected in the tendency to prefer immediate rewards over delayed rewards, is associated with most forms of problematic substance use. When assessed multiple times to examine within-individual changes, for example, following acute drug administration or an intervention, shifts in delay discounting simply because of repeated assessment is a concern, particularly when the assessment task is identical. This may be true for the Monetary Choice Questionnaire (MCQ), a widely used, fixed-item assessment of delay discounting. The present research examined possible within-individual difference/equivalence of MCQ indices at test/retest. This was contrasted with within-individual difference/equivalence when using an alternate version of the MCQ at retest, specifically developed to maintain the assessment structure and scoring of the original MCQ but with different choice items. Eighty-four participants completed delay discounting at test and retest with a 1-week interval; participants were randomized to complete the MCQ at both test and retest (MCQ/MCQ; n = 43) or complete the MCQ at test and an alternate version of the MCQ at retest (MCQ/MCQ-A; n = 41). Conventional hypothesis testing indicated no significant changes in delay discounting in the MCQ/MCQ condition or MCQ/MCQ-A condition. However, equivalence analysis, which is able to established whether scores are statistically equivalent, indicated that test/retest scores were not equivalent in some cases. Specifically, only 1 magnitude in the MCQ/MCQ condition was equivalent at test/retest, whereas 2 magnitudes in the MCQ/MCQ-A condition were equivalent at test/retest. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Impact of a Fieldwork Experience on Attitudes Toward People With Intellectual Disabilities.

OBJECTIVE: The objective of this study was to describe the effects of curriculum activities on changing attitudes of health professional students toward people with intellectual disabilities (IDs). METHOD: A nonrandomized, pretest-posttest design was used. Participants were college students assigned to one of three groups: two groups of students from different years in the occupational therapy program and one group of public health students. Each group completed the Attitudes Toward Intellectual Disabilities Questionnaire before and after each intervention. RESULTS: No significant differences were found in change of attitude after a lecture on the effects of stigma on people with disabilities. Length of time in program, age, and amount of experience with people with IDs affected changes in attitude for occupational therapy students after a fieldwork intervention. CONCLUSION: Level I fieldwork significantly improved the attitudes of occupational therapy students toward people with IDs, whereas a lecture did not.

Impact of construal level manipulations on delay discounting.

Construal Level Theory states that psychologically proximal outcomes are construed concretely while psychologically distal outcomes are construed abstractly. Previous research suggests that the principles of Construal Level Theory can be applied to enhance self-control, as measured by delay discounting. The present studies replicate and expand on this work by examining whether theory-informed priming manipulations lead to delay discounting reductions in a repeated-measures design. Study 1 conceptually replicated previous work, with reduced delay discounting observed as a function of thinking abstractly. Studies 2 and 3 expanded on this work by reinterpreting (a) preference for immediate outcomes as preference for outcomes that are construed concretely, and (b) dispreference for delayed outcomes as dispreference for outcomes that are construed abstractly. Study 2 provided support for the first interpretation, as reduced delay discounting was observed as a function of thinking concretely about the future. Study 3 provided support for the second interpretation, as reduced delay discounting was observed as a function of thinking abstractly about the present. In studies 1 and 3, significant condition × order interactions were observed. In all three studies, the same impact of order of exposure to priming manipulation was observed, indicating specific carryover effects.

Psychopathic individuals exhibit but do not avoid regret during counterfactual decision making.

Psychopathy is associated with persistent antisocial behavior and a striking lack of regret for the consequences of that behavior. Although explanatory models for psychopathy have largely focused on deficits in affective responsiveness, recent work indicates that aberrant value-based decision making may also play a role. On that basis, some have suggested that psychopathic individuals may be unable to effectively use prospective simulations to update action value estimates during cost-benefit decision making. However, the specific mechanisms linking valuation, affective deficits, and maladaptive decision making in psychopathy remain unclear. Using a counterfactual decision-making paradigm, we found that individuals who scored high on a measure of psychopathy were as or more likely than individuals low on psychopathy to report negative affect in response to regret-inducing counterfactual outcomes. However, despite exhibiting intact affective regret sensitivity, they did not use prospective regret signals to guide choice behavior. In turn, diminished behavioral regret sensitivity predicted a higher number of prior incarcerations, and moderated the relationship between psychopathy and incarceration history. These findings raise the possibility that maladaptive decision making in psychopathic individuals is not a consequence of their inability to generate or experience negative emotions. Rather, antisocial behavior in psychopathy may be driven by a deficit in the generation of forward models that integrate information about rules, costs, and goals with stimulus value representations to promote adaptive behavior.

Impact of episodic thinking on altruism.

Episodic future thinking, which refers to the use of prospective imagery to concretely imagine oneself in future scenarios, has been shown to reduce delay discounting (enhance self-control). A parallel approach, in which prospective imagery is used to concretely imagine other's scenarios, may similarly reduce social discounting (i.e., enhance altruism). In study 1, participants engaged in episodic thinking about the self or others, in a repeated-measures design, while completing a social discounting task. Reductions in social discounting were observed as a function of episodic thinking about others, though an interaction with order was also observed. Using an independent-measures design in study 2, the effect of episodic thinking about others was replicated. Study 3 addressed a limitation of studies 1 and 2, the possibility that simply thinking about others decreased social discounting. Capitalizing on Construal Level Theory, which specifies that social distance and time in the future are both dimensions of a common psychological distance, we hypothesized that episodic future thinking should also decrease social discounting. Participants engaged in episodic future thinking or episodic present thinking, in a repeated-measures design, while completing a social discounting task. The pattern of results was similar to study 1, providing support for the notion that episodic thinking about psychologically distant outcomes (for others or in the future) reduces social discounting. Application of similar episodic thinking approaches may enhance altruism.

Exchanging the liquidity hypothesis: Delay discounting of money and self-relevant non-money rewards.

Evidence that primary rewards (e.g., food and drugs of abuse) are discounted more than money is frequently attributed to money's high degree of liquidity, or exchangeability for many commodities. The present study provides some evidence against this liquidity hypothesis by contrasting delay discounting of monetary rewards (liquid) and non-monetary commodities (non-liquid) that are self-relevant and utility-matched. Ninety-seven (97) undergraduate students initially completed a conventional binary-choice delay discounting of money task. Participants returned one week later and completed a self-relevant commodity delay discounting task. Both conventional hypothesis testing and more-conservative tests of statistical equivalence revealed correspondence in rate of delay discounting of money and self-relevant commodities, and in one magnitude condition, less discounting for the latter. The present results indicate that liquidity of money cannot fully account for the lower rate of delay discounting compared to non-money rewards.

Bruton's Tyrosine Kinase Synergizes with Notch2 To Govern Marginal Zone B Cells in Nonobese Diabetic Mice.

Expansion of autoimmune-prone marginal zone (MZ) B cells has been implicated in type 1 diabetes. To test disease contributions of MZ B cells in NOD mice, Notch2 haploinsufficiency (Notch2(+/-)) was introduced but failed to eliminate the MZ, as it does in C57BL/6 mice. Notch2(+/-)/NOD have MZ B cell numbers similar to those of wild-type C57BL/6, yet still develop diabetes. To test whether BCR signaling supports Notch2(+/-)/NOD MZ B cells, Bruton's tyrosine kinase (Btk) deficiency was introduced. Surprisingly, MZ B cells failed to develop in Btk-deficient Notch2(+/-)/NOD mice. Expression of Notch2 and its transcriptional target, Hes5, was increased in NOD MZ B cells compared with C57BL/6 MZ B cells. Btk deficiency reduced Notch2(+/-) signaling exclusively in NOD B cells, suggesting that BCR signaling enhances Notch2 signaling in this autoimmune model. The role of BCR signaling was further investigated using an anti-insulin transgenic (Tg) BCR (125Tg). Anti-insulin B cells in 125Tg/Notch2(+/-)/NOD mice populate an enlarged MZ, suggesting that low-level BCR signaling overcomes reliance on Notch2. Tracking clonotypes of anti-insulin B cells in H chain-only VH125Tg/NOD mice showed that BTK-dependent selection into the MZ depends on strength of antigenic binding, whereas Notch2-mediated selection does not. Importantly, anti-insulin B cell numbers were reduced by Btk deficiency, but not Notch2 haploinsufficiency. These studies show that 1) Notch2 haploinsufficiency limits NOD MZ B cell expansion without preventing type 1 diabetes, 2) BTK supports the Notch2 pathway in NOD MZ B cells, and 3) autoreactive NOD B cell survival relies on BTK more than Notch2, regardless of MZ location, which may have important implications for disease-intervention strategies.

Bruton's tyrosine kinase promotes persistence of mature anti-insulin B cells.

Autoreactive B lymphocytes are essential for the development of T cell-mediated type 1 diabetes (T1D). Cytoplasmic Bruton's tyrosine kinase (BTK) is a key component of B cell signaling, and its deletion in T1D-prone NOD mice significantly reduces diabetes. However, the role of BTK in the survival and function of autoreactive B cells is not clear. To evaluate the contributions of BTK, we used mice in which B cells express an anti-insulin BCR (125Tg) and promote T1D, despite being anergic. Crossing Btk deficiency onto 125Tg mice reveals that, in contrast to immature B cells, mature anti-insulin B cells are exquisitely dependent upon BTK, because their numbers are reduced by 95%. BTK kinase domain inhibition reproduces this effect in mature anti-insulin B cells, with less impact at transitional stages. The increased dependence of anti-insulin B cells on BTK became particularly evident in an Igκ locus site-directed model, in which 50% of B cells edit their BCRs to noninsulin specificities; Btk deficiency preferentially depletes insulin binders from the follicular and marginal zone B cell subsets. The persistent few Btk-deficient anti-insulin B cells remain competent to internalize Ag and invade pancreatic islets. As such, loss of BTK does not significantly reduce diabetes incidence in 125Tg/NOD mice as it does in NOD mice with a normal B cell repertoire. Thus, BTK targeting may not impair autoreactive anti-insulin B cell function, yet it may provide protection in an endogenous repertoire by decreasing the relative availability of mature autoreactive B cells.

Patterns of widowhood mortality.

OBJECTIVES: Becoming widowed is a known risk factor for mortality. This article examines the magnitude of, explanations for, and variation in the association between widowhood and mortality. Previous research on widowhood mortality has revealed variation by socioeconomic status (SES), in that SES is not protective in widowhood, and by gender, such that men's mortality increases more than women's mortality after the death of spouse. METHOD: Using data from the Health and Retirement Study, we estimated Cox proportional hazard models to estimate the association between widowhood and mortality. RESULTS: Becoming widowed is associated with a 48% increase in risk of mortality. Approximately one third of the increase can be attributed to selection, in that those who become widows are socioeconomically disadvantaged. In contrast to previous studies, SES is protective for widows. Widowhood mortality risk increases for men if their wives' deaths were unexpected rather than expected; for women, the extent to which their husbands' death was expected matters less. DISCUSSION: Widowhood's harmful association with mortality show how strongly social support and individual's health and mortality are related. These findings support the larger literature on the importance of social support for health and longevity.

Tolerant anti-insulin B cells are effective APCs.

Autoreactive B lymphocytes that are not culled by central tolerance in the bone marrow frequently enter the peripheral repertoire in a state of functional impairment, termed anergy. These cells are recognized as a liability for autoimmunity, but their contribution to disease is not well understood. Insulin-specific 125Tg B cells support T cell-mediated type 1 diabetes in NOD mice, despite being anergic to B cell mitogens and T cell-dependent immunization. Using this model, the potential of anergic, autoreactive B cells to present Ag and activate T cells was investigated. The data show that 1) insulin is captured and rapidly internalized by 125Tg BCRs, 2) these Ag-exposed B cells are competent to activate both experienced and naive CD4(+) T cells, 3) anergic 125Tg B cells are more efficient than naive B cells at activating T cells when Ag is limiting, and 4) 125Tg B cells are competent to generate low-affinity insulin B chain epitopes necessary for activation of diabetogenic anti-insulin BDC12-4.1 T cells, indicating the pathological relevance of anergic B cells in type 1 diabetes. Thus, phenotypically tolerant B cells that are retained in the repertoire may promote autoimmunity by driving activation and expansion of autoaggressive T cells via Ag presentation.

Intergenerational transmission of reproductive behavior during the demographic transition.

New evidence from the Utah Population Database (UPDP) reveals that at the onset of the fertility transition, reproductive behavior was transmitted across generations - between women and their mothers, as well as between women and their husbands' family of origin. Age at marriage, age at last birth, and the number of children ever born are positively correlated in the data, most strongly among first-born daughters and among cohorts born later in the fertility transition. Intergenerational ties, including the presence of mothers and mothers-in-law, influenced the hazard of progressing to a next birth. The findings suggest that the practice of parity-dependent marital fertility control and inter-birth spacing behavior derived, in part, from the previous generation and that the potential for mothers and mothers-in-law to help in the rearing of children encouraged higher marital fertility.

Mortality Differentials and Religion in the U.S.: Religious Affiliation and Attendance.

Using data from the Health and Retirement Study, I examine the relationship between adult mortality and religious affiliation. I test whether mortality differences associated with religious affiliation can be attributed to differences in socioeconomic status (years of education and household wealth), attendance at religious services, or health behaviors, particularly cigarette and alcohol consumption. A baseline report of attendance at religious services is used to avoid confounding effects of deteriorating health. Socioeconomic status explains some but not all of the mortality difference. While Catholics, Evangelical Protestants, and Black Protestants benefit from favorable attendance patterns, attendance (or lack of) at services explains much of the higher mortality of those with no religious preference. Health behaviors do not mediate the relationship between mortality and religion, except among Evangelical Protestants. Not only does religion matter, but studies examining the effect of "religiosity" need to consider differences by religious affiliation.