Hospital-Acquired Infection at Time of Stroke and Cognitive Decline: The Cardiovascular Health Study.

Introduction Hospital-acquired infections (HAIs) after stroke are associated with additional morbidity and mortality, but whether HAIs increase long-term cognitive decline in stroke patients is unknown. We hypothesized that older adults with incident stroke with HAI experience faster cognitive decline than those having stroke without HAI and those without stroke. Methods We performed a longitudinal analysis in the population-based prospective Cardiovascular Health Study. Medicare-eligible participants aged >65 years with and without incident stroke had cognition assessed annually. HAIs were assessed by hospital discharge codes. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) and executive function by Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate the mean decline and 95% confidence intervals (95% CI) for 3MSE and DSST scores by incident stroke and HAI status, adjusted for demographics and vascular risk factors. Results Among 5,443 participants >65 years without previous history of stroke, 393 participants had stroke with HAI (SI), 766 had a stroke only (SO), and 4,284 had no stroke (NS) throughout a maximum 9-year follow-up. For 3MSE, compared with NS participants, SO participants had a similar adjusted mean decline (additional 0.08 points/year, 95%CI -0.15, 0.31), while SI participants had a more rapid decline (additional 0.28 points/year, 95%CI 0.16, 0.40). Adjusted mean decline was 0.20 points/year faster (95%CI -0.05, 0.45) among SI than SO participants. For DSST, compared with NS participants, SO participants had a faster adjusted mean decline (additional 0.17 points/year (95%CI 0.003, 0.33), as did SI participants (additional 0.27 points/year (95%CI 0.19, 0.35). Conclusion Stroke, when accompanied by HAI, leads to a faster long-term decline in cognitive ability than in those without stroke. The clinical and public health implications of the effect of infection on post-stroke cognitive decline warrant further attention.

Gender-Specific Interactions in a Visual Object Recognition Task in Persons with Opioid Use Disorder.

Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men reported at twice the rate for women. Using a controlled, cross-sectional, age-matched (18-56 y) design to better understand the cognitive neuroscience of OUD, we evaluated the electroencephalographic (EEG) responses of male and female participants with OUD vs. age- and gender-matched non-OUD controls during a simple visual object recognition Go/No-Go task. Overall, women had significantly slower reaction times (RTs) than men. In addition, EEG N200 and P300 event-related potential (ERP) amplitudes for non-OUD controls were significantly larger for men, while their latencies were significantly shorter than for women. However, while N200 and P300 amplitudes were not significantly affected by OUD for either men or women in this task, latencies were also affected differentially in men vs. women with OUD. Accordingly, for both N200 and P300, male OUD participants exhibited longer latencies while female OUD participants exhibited shorter ones than in non-OUD controls. Additionally, robust oscillations were found in all participants during a feedback message associated with performance in the task. Although alpha and beta power during the feedback message were significantly greater for men than women overall, both alpha and beta oscillations exhibited significantly lower power in all participants with OUD. Taken together, these findings suggest important gender by OUD differences in cognitive processing and reflection of performance in this simple visual task.

Cognitive function in UK adults seropositive for Helicobacter pylori.

Associated with gastritis, peptic-ulcer disease, and gastric carcinoma, Helicobacter pylori (H. pylori) also has been associated with decreased cognitive function and dementia. In this study, we used data from the UK Biobank to further examine associations between H. pylori seropositivity and serointensity and performance on several cognitive tasks in adults 40 to 70 years of age (M = 55.3, SD = 8.1). In these analyses, H. pylori seropositivity (i.e., either positive or negative for H. pylori) and serointensity (concentration of antibodies against H. pylori antigens) in adjusted models were associated with worse function on tasks of Numeric memory, Reasoning, and errors on the Pairs matching test but better function on the Tower rearrangement task. Together, these findings suggest that H. pylori seropositivity and serointensity might be associated with worse cognitive function in this age group.

Gap in the conditioned stimulus: Differential impacts on temporal expectancy in appetitive and aversive conditions in rats.

We analyzed, through a Pavlovian conditioning procedure in rats, the temporal pattern of behavior in appetitive and aversive conditions within subjects, and the difference in inferred temporal working memory functioning with the Gap paradigm. For both conditions, we paired a 60-s conditioned stimulus (CS: tone1 or tone2) with an unconditioned stimulus (US: shock or chocolate pellet) delivered 20s after CS onset. The analyses of mean response rate and individual-trial data were performed during Probe trials, consisting of CS alone, and trials in which gaps of different position or duration were inserted, to assess the effect of the temporal manipulation on behavior. The results showed: (1) An anticipatory peak time in the aversive condition but better accuracy in the appetitive condition, (2) constancy in the Weber fraction suggesting that the difference in peak time was under clock control, (3) a graded effect of gap parameters only in the aversive condition and (4) different gap effects between conditions when a gap was inserted early in the CS. These results highlight behavioral differences between aversive and appetitive conditions and suggest that the temporal working memory mechanism was not engaged in the same manner in each condition.

Association between toxocariasis seropositivity and serointensity and cognitive function in older U.S. adults.

The nematodes Toxocara canis (Werner, 1782) and Toxocara cati (Schrank, 1788) have been associated with worse human cognitive function in children and middle-aged adults. In this study, we sought to determine the association between Toxocara seropositivity and serointensity determined by detection of IgG antibodies against the Toxocara antigen recombinant Tc-CTL-1 and cognitive function in older adults, including approximately 1,350 observations from the 2013-2014 National Health and Nutrition Examination Survey. Mean fluorescence intensity was used to quantify IgG antibodies against the Toxocara recombinant Tc-CTL-1 antigen, and respondents were considered positive at values greater than 23.1. In adjusted models from sample sizes ranging from 1,274 to 1,288 depending on the individual cognitive task, we found that Toxocara seropositivity was associated with worse performance on the animal-fluency task (b = -1.245, 95% CI: -2.392 to -0.099, P< 0.05) and the digit-symbol coding task (b = -5.159, 95% CI: -8.337 to -1.980, P< 0.001). Toxocara serointensity assessed using log-transformed mean fluorescence intensity as a continuous variable was associated with worse performance on the digit-symbol coding task (b = -1.880, 95% CI: -2.976 to -0.783, P < 0.001). There were no significant associations with tasks assessing memory. Further, age modified the association between Toxocara and cognitive function, although sex, educational attainment, and income did not. These findings suggest that Toxocara might be associated with deficits in executive function and processing speed in older U.S. adults, although additional research is required to better describe cognitive function in older adults who are seropositive for Toxocara spp.

Cytomegalovirus is not associated with cognitive function in UK adults aged 40 to 70 years.

Infecting much of the world's population, the herpesviridae virus cytomegalovirus has been associated with lower cognitive function in some but not all studies. In this study, we further investigate associations between cytomegalovirus and cognitive function in a community-based sample of adults aged 40 to 70 years (M = 55.3; SD = 8.1) from the United Kingdom. Adjusted multiple-regression modeling showed no significant associations between cytomegalovirus and performance on nine cognitive tasks. Further, in adjusted interaction models, age, sex, educational attainment, and income did not moderate associations between cytomegalovirus and cognitive function. In this community-based adult sample, cytomegalovirus was not associated with cognitive function.

Association between Cognitive Function and Depression with Human T-Cell Lymphotropic Virus 1 Seropositivity and Serointensity in UK Adults.

Several viral, bacterial, and parasitic diseases have been associated with cognitive function and neuropsychiatric outcomes in humans, including human T-cell lymphotropic virus 1 (HTLV-1). In this study, we sought to further generalize previously reported associations of cognitive function and depression with HTLV-1 seropositivity and serointensity using a community-based sample of adults aged approximately 40 to 70 years (mean = 55.3 years) from the United Kingdom. In this sample, the results of adjusted linear regression models showed no associations of HTLV-1 seropositivity or serointensity with reasoning, pairs-matching, or reaction-time cognitive tasks or with depression. In addition, neither age, sex, educational attainment, nor income moderated associations of HTLV-1 seropositivity or serointensity with cognitive function or depression. In this middle-aged to older middle-aged adult community sample, HTLV-1 seropositivity and serointensity do not appear to be associated with reasoning, pairs-matching, and reaction-time tasks or with depression.

GenoRisk: A polygenic risk score for Alzheimer's disease.

INTRODUCTION: Recent clinical trials are considering inclusion of more than just apolipoprotein E (APOE) ε4 genotype as a way of reducing variability in analysis of outcomes. METHODS: Case-control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)-associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross-validation. Genotype and sex × age estimates from the best performing model were combined with age and intercept estimates from the general population to develop a personalized genetic risk score, termed age, and sex-adjusted GenoRisk. RESULTS: The elastic net model that included age, age x sex interaction, allelic APOE terms, and 29 additional SNPs performed the best. This model explained an additional 19% of the heritable risk compared to APOE genotype alone and achieved an area under the curve of 0.747. DISCUSSION: GenoRisk could improve the risk assessment of individuals identified for prevention studies.

Examining the Relationship between Toxoplasma gondii and Seropositivity and Serointensity and Depression in Adults from the United Kingdom and the United States: A Cross-Sectional Study.

Infecting approximately one-third of the world's population, the neurotropic protozoan Toxoplasma gondii has been associated with cognition and several neuropsychiatric diseases including schizophrenia and bipolar disorder. Findings have been mixed, however, about the relationship between Toxoplasma gondii and depression, with some studies reporting positive associations and others finding no associations. To further investigate the association between Toxoplasma gondii and depression, we used data from the UK Biobank and the National Health and Examination Survey (NHANES). Results from adjusted multiple-regression modeling showed no significant associations between Toxoplasma gondii and depression in either the UK Biobank or NHANES datasets. Further, we found no significant interactions between Toxoplasma gondii and age, sex, educational attainment, and income in either dataset that affected the association between Toxoplasma gondii and depression. These results from two community-based datasets suggest that in these samples, Toxoplasma gondii is not associated with depression. Differences between our findings and other findings showing an association between Toxoplasma gondii and depression could be due to several factors including differences in socioeconomic variables, differences in Toxoplasma gondii strain, and use of different covariates in statistical modeling.

Association between Toxoplasma gondii seropositivity and serointensity and brain volume in adults: A cross-sectional study.

The intracellular protozoal parasite Toxoplasma gondii has been associated with worsened cognitive function in animal models and in humans. Despite these associations, the mechanisms by which Toxoplasma gondii might affect cognitive function remain unknown, although Toxoplasma gondii does produce physiologically active intraneuronal cysts and appears to affect dopamine synthesis. Using data from the UK Biobank, we sought to determine whether Toxoplasma gondii is associated with decreased prefrontal, hippocampal, and thalamic gray-matter volumes and with decreased total gray-matter and total white-matter volumes in an adult community-based sample. The results from adjusted multivariable regression modelling showed no associations between Toxoplasma gondii and prefrontal, hippocampal, and thalamic brain gray-matter volumes. In contrast, natural-log transformed antibody levels against the Toxoplasma gondii p22 (b = -3960, 95-percent confidence interval, -6536 to -1383, p < .01) and sag1 (b = -4863, 95-percent confidence interval, -8301 to -1425, p < .01) antigens were associated with smaller total gray-matter volume, as was the mean of natural-log transformed p22 and sag1 titers (b = -6141, 95-percent confidence interval, -9886 to -2397, p < .01). There were no associations between any of the measures of Toxoplasma gondii and total white-matter volume. These findings suggest that Toxoplasma gondii might be associated with decreased total gray-matter in middle-aged and older middle-aged adults in a community-based sample from the United Kingdom.

Toxoplasma gondii seropositivity and serointensity and cognitive function in adults.

Infecting approximately one-third of the world's human population, Toxoplasma gondii has been associated with cognitive function. Here, we sought to further characterize the association between Toxoplasma gondii and cognitive function in a community sample of adults aged approximately 40 to70 years. Using adjusted linear regression models, we found associations of Toxoplasma gondii seropositivity with worse reasoning (b = -.192, p < .05) and matrix pattern completion (b = -.681, p < .01), of higher anti-Toxoplasma gondii p22 antibody levels with worse reasoning (b = -.078, p < .01) and slower Trails (numeric) performance (b = 5.962, p < .05), of higher anti-Toxoplasma gondii sag1 levels with worse reasoning (b = -.081, p < .05) and worse matrix pattern completion (b = -.217, p < .05), and of higher mean of the anti-Toxoplasma gondii p22 and sag1 levels with worse reasoning (b = -.112, p < .05), slower Trails (numeric) performance (b = 9.195, p < .05), and worse matrix pattern completion (b = -.245, p < .05). Neither age nor educational attainment moderated associations between the measures of Toxoplasma gondii seropositivity or serointensity. Sex, however, moderated the association between the sag1 titer and digit-symbol substitution and the association between the mean of the p22 and sag1 levels and digit-symbol substitution, and income moderated the association between Toxoplasma gondii seropositivity and numeric memory and the association between the p22 level and symbol-digit substitution. Based on the available neuropsychological tasks in this study, Toxoplasma gondii seropositivity and serointensity were associated with some aspects of poorer executive function in adults.

Non-symmetrical effects in the temporal bisection after selective food devaluation in rats.

The present study investigated the effects of selective food devaluation on performance in the temporal bisection procedure with rats. Differential outcomes (sucrose vs. grain pellets) were associated with correct responding for a short and a long duration in order to analyze the effects of a selective duration-specific food devaluation on the temporal bisection function. Selective prefeeding produced differential changes in proportion of responding, the p(long) function, and PSE. A more consistent impact was observed when the food associated with the long anchor duration was devalued than when the short anchor duration food was devalued. The results are discussed in relation to the bias as well as a choose-short effect.

Association between exposure to air pollution and thalamus volume in adults: A cross-sectional study.

BACKGROUND: Air pollution has been associated with cognitive function and brain volume. While most previous research has examined the association between air pollution and brain volume in cortical structures or total brain volume, less research has investigated associations between exposure to air pollution and subcortical structures, including the thalamus. Further, the few available previous studies investigating associations between air pollution and thalamic volume have shown mixed results. METHODS: In this study, we evaluated the association between PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides and volume of the thalamus in adults using the UK Biobank resource, a large community-based sample, while adjusting for multiple covariates that could confound an association between air pollution and thalamic volume. RESULTS: In adjusted models, the left but not right thalamus volume was significantly inversely associated with PM2.5-10, although there were no significant associations between PM2.5, PM10, nitrogen dioxide, and nitrogen oxides with either left or right thalamic volumes. In addition, interactions between age and PM2.5-10 and PM10 were inversely associated with thalamic volume, such that thalamic volume in older people appeared more vulnerable to the adverse effects of PM2.5-10 and PM10, and interactions between educational attainment and PM2.5, nitrogen dioxide, and nitrogen oxides and between self-rated health and PM2.5-10 were positively associated with thalamic volume, such that higher educational attainment and better self-rated health appeared protective against the adverse effects of air pollution on the thalamus. CONCLUSION: These findings suggest a possible association between thalamic volume and air pollution particularly in older people and in people with comparatively low educational attainment at levels of air pollution found in the United Kingdom.

Association between exposure to air pollution and prefrontal cortical volume in adults: A cross-sectional study from the UK biobank.

Associated with numerous cognitive and behavioral functions and with several diseases, the prefrontal cortex is vulnerable to environmental insult. Among other factors, toxins in air pollution have been associated with damage to the prefrontal cortex in children and older adults. We used data from the UK Biobank to assess further associations between an array of toxins in air pollution and gray matter in the prefrontal cortex including the left and right frontal poles, left and right superior frontal gyri, left and right frontal medial cortex, left and right orbitofrontal cortex, and left and right frontal opercula, using multivariate models adjusted for covariates that possibly could confound the association between air pollution and volume of prefrontal gray matter. The results showed inverse associations between PM 2.5, PM 10, and nitrogen oxides and prefrontal volume in models adjusted for age, sex, education, socioeconomic status, race-ethnicity, self-rated overall health, body mass index, total brain volume, smoking status, and alcohol use frequency. Education appeared to moderate the association between air pollution and prefrontal volume. The data in these analyses came from regions whose mean PM 2.5 was near the upper limit and whose mean PM 10 was under those recommended by the World Health Organization. These findings suggest that comparatively low levels of air pollution might be associated with reduced volume of the prefrontal cortex.

Association between Exposure to Air Pollution and Total Gray Matter and Total White Matter Volumes in Adults: A Cross-Sectional Study.

Total brain gray-matter and white-matter volumes can be indicators of overall brain health. Among the factors associated with gray-matter and white-matter volumes is exposure to air pollution. Using data from the UK Biobank, we sought to determine associations between several components of air pollution-PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides-and total gray-matter and total white-matter volumes in multivariable regression models in a large sample of adults. We found significant inverse associations between PM2.5 concentration and total white-matter volume and between PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxide concentrations and total gray-matter volume in models adjusted for age, sex, body-mass index, self-assessment of overall health, frequency of alcohol use, smoking status, educational attainment, and income. These findings of pollutant-associated decreases in total gray-matter and total white-matter volumes are in the context of mean PM2.5 concentrations near the upper limit of the World Health Organization's recommendations. Similarly, mean PM10 concentrations were below the recommended upper limit, and nitrogen dioxide concentration was slightly above. Still, there are many areas in the world with much higher concentrations of these pollutants, which could be associated with larger effects. If replicated, these findings suggest that air pollution could be a risk factor for neurodegeneration.

Data from timing fear cues in the temporal bisection task.

Research on emotion often involves the use of emotion-evoking stimuli that are used to manipulate emotional state across groups or conditions. One standardized set of stimuli that has been used for this purpose is the International Affective Picture System (IAPS) [1]. The data described in this article were obtained over the course of two experiments in which the primary task was for participants to judge the presentation duration of six IAPS pictures in the temporal bisection task [2-4]. Each of these experiments contained three types of phases (rating, training, and testing). In rating phases, participants rated the IAPS pictures for evoked valence, arousal, and fear. In training phases, participants were trained to classify the presentation duration of green squares (Experiment 1) or IAPS pictures (Experiment 2) as either "short" or "long." In testing phases, participants were instructed to use what they had learned in the preceding training phases to classify the IAPS pictures as either "short" or "long." The findings related to these data were published in Grommet, Hemmes, and Brown [5], and the data are available in Mendeley Data, DOI: 10.17632/xx6zh6mmjw.1 [6].

Association between exposure to air pollution and hippocampal volume in adults in the UK Biobank.

BACKGROUND: The hippocampus is important for memory processing. Several neuropsychiatric diseases including Alzheimer's disease are associated with reduced hippocampal volume, and further the hippocampus appears vulnerable to environmental insult. Air pollution has been associated with cardiovascular disease, abnormal brain structure, and cognitive deficits. OBJECTIVE: Because of hippocampal vulnerability to environmental insults and based on the association between exposure to air pollution and cognitive function and brain structure, we evaluated the association between exposure to toxins in air pollution and left and right hippocampal volume using brain-imaging and air-pollution data from the UK Biobank, a large community-based dataset. METHODS: We used regression modelling to evaluate the association between exposure to nitrogen dioxide, nitrogen oxides, PM2.5, PM2.5-10, and PM10. and left and right hippocampal volume controlling for age, sex, body-mass index, overall health, alcohol use, smoking, educational attainment, socioeconomic status, inverse distance from the nearest major road, and a measure of total brain volume. RESULTS: In these models, PM2.5 concentration was associated with smaller left hippocampal volume. None of the other measures of air pollution was associated with either left or right hippocampal volume, although interaction models provided some evidence that sex might moderate the relationship between air pollution and hippocampal volume. In adjusted models, age, sex, educational attainment, income, overall health, current smoking, alcohol intake, and body-mass index were associated with hippocampal volume. CONCLUSIONS: PM2.5 at levels found in the United Kingdom was associated with smaller left hippocampal volume. Additional associations between several covariates and hippocampal volumes indicate that hippocampal volume might be associated with several potentially modifiable variables.

Cardiovascular factors moderate the association of infection burden with cognitive function in young to middle-aged U.S. adults.

BACKGROUND: Infectious diseases might affect cognitive aging and dementia risk, possibly via neuroinflammation. Similarly, risk factors for cardiovascular and cerebrovascular diseases are associated with cognitive function and dementia. We hypothesized that cardiovascular risk factors moderate the association of exposure to infectious diseases with cognitive function. METHODS: We studied 5662 participants aged 20 to 59 years from the third National Health and Nutrition Examination Survey (1988-1994) in the United States. We used linear regression to investigate whether the Framingham general cardiovascular risk index moderated the association of infection burden based on exposure to eight different infectious diseases with cognitive functioning as measured by the Symbol Digit Substitution, Serial Digit Learning, and Reaction Time tests. RESULTS: The multiplicative interaction between the infection-burden index and the cardiovascular-risk index was associated with performance on the Symbol Digit Substitution (B = .019 [95% CI: .008, .031], p < .001) but not on the Serial Digit Learning (B = .034 [95% CI: -.025, .094]) or for Reaction Time (B = -.030 [95% CI: -.848, .787]). Participants with a lower cardiovascular risk appeared to be more resilient against the potential adverse effects of higher infection burden on the Symbol Digit Substitution task. CONCLUSIONS: Participants at zero risk for a cardiovascular event in the next 10 years had no differences in processing speed with increasing exposure to infectious disease, whereas participants with higher risk for a cardiovascular event had worse processing speed with increased exposure to infectious disease.

The Role of Clock and Memory Processes in the Timing of Fear Cues by Humans in the Temporal Bisection Task.

Recent research on the effects of fear on timing has focused on two accounts proposed by Scalar Expectancy Theory for why the durations of fear stimuli are overestimated in comparison to the durations of neutral stimuli. One possibility is that fear serves as an arouser that increases the speed of a hypothetical internal clock. The other possibility is that fear increases attention to time, which results in organisms' beginning to time fear-evoking stimuli sooner than they do neutral stimuli. In Experiment 1, we asked which of these two possibilities was the underlying mechanism of temporal overestimation of fear cues by presenting emotion-evoking pictures (fear-evoking vs. neutral) across multiple duration ranges in the temporal bisection task. Larger effects of fear were observed at the longest duration range in comparison to the shortest duration range, supporting the arousal hypothesis. Penney et al. 1998 and Penney et al., 2000 memory-mixing hypothesis proposes that overestimation is only possible in preparations that allow for recalled reference memories for stimulus durations to be mixed across conditions. Therefore, in Experiment 2, we manipulated whether or not fear and neutral cues were presented within the same session, a condition that may be necessary for memory mixing to occur. Fear cues were overestimated relative to neutral cues within the session in which fear and neutral cues were both presented, but no effect of emotion was observed between the two sessions in which fear and neutral cues were presented separately.

Duration-specific effects of outcome devaluation in temporal control are differentially sensitive to amount of training.

This study demonstrates that overtraining in temporal discrimination modifies temporal stimulus control in a bisection task and produces habitual responding, as evidenced through insensitivity to food devaluation. Rats were trained or overtrained in a 2- versus 8-sec temporal discrimination task, with each duration associated with a lever (left or right) and food (grain or sucrose). Overtraining produced a leftward shift in the bisection point. Devaluation treatment induced a differential loss of responding depending on stimulus duration (short versus long) and the level of training (training versus overtraining). The relationships between timing behavior and habitual behavior are discussed.