Infection burden, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer's disease dementia in a large national survey.

INTRODUCTION: Relationships and interplay of an infection burden (IB) and periodontal pathogens or periodontal disease (Pd) markers with Alzheimer's disease (AD) and all-cause dementia among US adults were examined. METHODS: Less than or equal to 2997 participants from the National Health and Nutrition Survey III were linked to CMS-Medicare [≥45 years (1988-1994); ≤30 years follow-up]. RESULTS: Hepatitis C (hazard ratio = 3.33, p = 0.004) and herpes simplex virus 2 were strongly associated with greater all-cause dementia risk. Porphyromonas gingivalis and Streptococcus oralis were associated with greater AD risk at higher IB. The red-green periodontal pathogen cluster coupled with higher IB count increased the risk of all-cause dementia among minority racial groups. Pocket probing depth associated with dementia risk at lower IB in the overall sample. DISCUSSION: Select viruses and bacteria were associated with all-cause and AD dementia, while the IB interacted with Pd markers in relation to these outcomes. HIGHLIGHTS: Interplay of infection burden (IB) and periodontal disease with dementia was tested. ≤2997 participants from NHANES III were linked to Medicare. Hepatitis C and herpes simplex virus 2 strongly associated with dementia risk. Tetanus sero-positivity increased Alzheimer's disease (AD) risk. Porphyromonas gingivalis and Streptococcus oralis associated with AD at higher IB. Red-green periodontal cluster at high IB, increased dementia in racial minorities. Pocket probing depth associated with dementia risk at lower IB.

Cardiovascular health, infection burden and their interactive association with brain volumetric and white matter integrity outcomes in the UK Biobank.

BACKGROUND: Cardiovascular health is associated with brain magnetic resonance imaging (MRI) markers of pathology and infections may modulate this association. METHODS: Using data from 38,803 adults (aged 40-70 years) and followed-up for 5-15 years, we tested associations of prevalent total (47.5%) and hospital-treated infection burden (9.7%) with brain structural and diffusion-weighted MRI (i.e., sMRI and dMRI, respectively) common in dementia phenome. Poor white matter tissue integrity was operationalized with lower global and tract-specific fractional anisotropy (FA) and higher mean diffusivity (MD). Volumetric sMRI outcomes included total, gray matter (GM), white matter (WM), frontal bilateral GM, white matter hyperintensity (WMH), and selected based on previous associations with dementia. Cardiovascular health was measured with Life's Essential 8 score (LE8) converted to tertiles. Multiple linear regression models were used, adjusting for intracranial volumes (ICV) for subcortical structures, and for demographic, socio-economic, and the Alzheimer's Disease polygenic risk score for all outcomes, among potential confounders. RESULTS: In fully adjusted models, hospital-treated infections were inversely related to GM (ß ± SE: -1042 ± 379, p = 0.006) and directly related to WMH as percent of ICV (Loge transformed) (ß ± SE:+0.026 ± 0.007, p < 0.001). Both total and hospital-treated infections were associated with poor WMI, while the latter was inversely related to FA within the lowest LE8 tertile (ß ± SE:-0.0011 ± 0.0003, p < 0.001, PLE8×IB < 0.05), a pattern detected for GM, Right Frontal GM, left accumbens and left hippocampus volumes. Within the uppermost LE8 tertile, total infection burden was linked to smaller right amygdala while being associated with larger left frontal GM and right putamen volumes, in the overall sample. Within that uppermost tertile of LE8, caudate volumes were also positively associated with hospital-treated infections. CONCLUSIONS: Hospital-treated infections had more consistent deleterious effects on volumetric and white matter integrity brain neuroimaging outcomes compared with total infectious burden, particularly in poorer cardiovascular health groups. Further studies are needed in comparable populations, including longitudinal studies with multiple repeats on neuroimaging markers.

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.

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.

Predicting eye-movement characteristics across multiple tasks from working memory and executive control.

Individual differences in working memory (WM) and executive control are stable, related to cognitive task performance, and clinically predictive. Between-participant differences in eye movements are also highly reliable (Carter & Luke, Journal of Experimental Psychology: Human Perception and Performance, 2018; Henderson & Luke, Journal of Experimental Psychology: Human Perception and Performance, 40(4), 1390-1400, 2014). However, little is known about how higher order individual differences in cognition are related to these eye-movement characteristics. In the present study, healthy college-age participants performed several individual difference tasks to measure WM span and executive control. Participants also performed three eye-movement tasks: reading, visual search, and scene viewing. Across all tasks, higher WM scores were related to reduced skewness in fixation duration distributions. In reading, higher WM scores predicted longer saccades. In scene viewing, higher WM scores predicted longer fixations. Theoretical and clinical implications of these findings are discussed.

Toxoplasma gondii seropositivity and substance use in US adults.

The intracellular parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) infects humans resulting in acute toxoplasmosis, an infection that in immunocompetent people is typically mild but results in persistent latent toxoplasmosis. In that T. gondii appears to affect dopamine synthesis and because addicting drugs affect midbrain dopamine transmission, latent toxoplasmosis could influence substance use. Using both the third and continuous National Health and Nutrition Examination Surveys from the US Centers for Disease Control and Prevention, we used logistic regression to test for associations between T. gondii seropositivity and subject self-report of having ever used tobacco, alcohol, marijuana, cocaine, heroin, or methamphetamine. In the third NHANES dataset, which included data for tobacco, alcohol, marijuana and cocaine, T. gondii seropositivity was associated with a reduced likelihood of self-reported marijuana (OR = 0.71 [95% CI: 0.58; 0.87]; p = 0.001) and cocaine use (OR = 0.72 [95% CI: 0.56; 0.91]; p = 0.006). In the continuous National Health and Nutrition Examination Surveys dataset, which included data for all six substances, T. gondii seropositivity was associated with a reduced likelihood of self-reported tobacco (OR = 0.87 [95% CI: 0.76; 1.00]; p = 0.044), marijuana (OR = 0.60 [95% CI: 0.50; 0.72]; p < 0.001), heroin (OR = 0.60 [95% CI: 0.42; 0.85]; p = 0.005) and methamphetamine use (OR = 0.54 [95% CI: 0.38; 0.77]; p = 0.001). We observed interactions between sex and T. gondii seropositivity in the prediction of self-reported use of tobacco and alcohol. Further, T. gondii seropositivity appeared to remove the protective effect of education and economic status against self-reported cigarette smoking. These findings suggest that T. gondii seropositivity may be inversely associated with some but not all types of substance use in US adults.

Long-term cognitive and neuroanatomical stability in patients with anoxic amnesia: A Case Report.

BACKGROUND: Anoxia can result in selective hippocampal damage with associated impairments in declarative memory. Whilst memory impairments and brain structures are thought to be stable, there are little data regarding the effects of ageing or change over time in patients with amnesia from anoxic brain injury. METHODS: To assess change over time, we compared structural magnetic resonance imaging (MRI) with data obtained over ten years previously in two well-characterized patients with amnesia (JRW and RS) who experienced an anoxic brain injury. Six healthy, age-matched control participants were recruited to compare brain volumes with the patients at Time 2. Wechsler adult intelligence scale-revised and Wechsler memory scale-revised scores were compared to scores on the same tests administered 13 and 19 years prior. RESULTS: Patients with amnesia had significantly smaller hippocampal volumes than controls, but comparable medial temporal lobe and ventricular volumes. Memory, intellectual function and brain volumes were stable over time. CONCLUSION: Patients with an amnesia due to anoxia have memory impairments and smaller hippocampal volumes compared to controls; however, memory, intelligence and structural volumes remain stable over time. At ages 50 and 57, they do not appear to have early age-associated cognitive decline that is sometimes observed in patients with traumatic brain injury.

Infectious disease burden and cognitive function in young to middle-aged adults.

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults.

Folate and Inflammatory Markers Moderate the Association Between Helicobacter pylori Exposure and Cognitive Function in US Adults.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with cognitive deficits in humans, an association potentially mediated or moderated by folate concentration or inflammation. MATERIALS AND METHODS: We used the National Health and Nutrition Examination Survey (NHANES) datasets to examine whether folate concentration or inflammation mediates or moderates the relationship between H. pylori and cognitive function. Models were performed using linear, Poisson, and zero-inflated Poisson regression, and we performed separate analyses for groups aged 20-59 and 60-90 years with sample sizes ranging from 700 to 1700. RESULTS: We did not find evidence of mediation in either age group. In the 20- to 59-year group, interactions between H. pylori and ferritin (p values ranging from .004 to .039) were associated with worse processing speed, better working memory, and worse reaction time. Interactions between H. pylori and fibrinogen (p values ranging from .023 to .045), C-reactive protein (CRP) (p = .023), and the inflammatory index (p = .045) were associated with worse processing speed. In 60- to 90-year-olds, H. pylori interacted with ferritin and the inflammatory index to predict fewer mathematical errors (p values of .036 and .023). Interactions with folate (p values of .016 and .006) and C-reactive protein (p values ranging from <.001 to .048) were inconsistent in directionality. CONCLUSIONS: In this dataset, representative of the US population, inflammation and folate concentrations moderated but did not mediate the association between H. pylori seropositivity and cognition.

Executive Function in Pediatric Sleep-Disordered Breathing: A Meta-analysis.

OBJECTIVES: Evaluate the association between pediatric sleep-disordered breathing (SDB) and executive functioning. METHODS: We searched multiple electronic databases for peer-reviewed journal articles related to pediatric SDB and executive functioning. We included studies that assessed SDB via polysomnography, included objective or questionnaire measures of executive function, and had an age-matched control group. Fourteen articles met inclusion criteria with a total sample of 1697 children ages 5 to 17 years (M=9.81 years; SD=0.34). We calculated an overall effect size for each of the five executive domains (vigilance, inhibition, working memory, shifting, and generativity) as well as effect sizes according to SDB severity: mild, moderate, severe. We also calculated effect sizes separately for objective and subjective questionnaires of executive functioning. RESULTS: We found a medium effect size (-0.427) for just one of five executive function domains on objective neuropsychological measures (generativity). In contrast, effect sizes on all three executive domains measured via questionnaire data were significant, with effect sizes ranging from medium (-0.64) to large (-1.06). We found no difference between executive domains by severity of SDB. CONCLUSIONS: This meta-analysis of executive function separated into five domains in pediatric SDB suggested lower performance in generativity on objective neuropsychological measures. There were no differences associated with SDB severity. Questionnaire data suggested dysfunction across the three executive domains measured (inhibition, working memory, shifting). Overall, limited evidence suggested poorer performance in executive function in children with SDB according to objective testing, and subjective ratings of executive function suggested additional worsened performance. (JINS, 2016, 22, 839-850).

Seroprevalence and Serointensity of Latent Toxoplasma gondii in a Sample of Elderly Adults With and Without Alzheimer Disease.

INTRODUCTION: Latent infection with Toxoplasma gondii has been associated with behavioral and cognitive changes in animal models and in humans. Early findings have suggested an association between latent toxoplasmosis and Alzheimer disease (AD). On the basis of these factors, we sought to determine whether there is an association between latent toxoplasmosis and AD using a large, well-characterized sample of subjects with AD and age-matched and sex-matched controls without dementia. METHODS: Using ELISA, we determined anti-T. gondii IgG antibody titers in 114 control subjects and in 105 subjects diagnosed with AD through an Alzheimer's Disease Research Center. RESULTS: There were no group differences between groups in age, ethnicity, or sex. Education and socioeconomic status was slightly higher in the control group. Neither the prevalence of anti-T. gondii IgG antibodies (33% in the nondemented control group compared with 41% in the AD group, P=0.25) nor log-transformed antibody concentration (106.6 IU/mL in the control group compared with 140.9 IU/mL in the AD group, P=0.85) differed between the control and AD groups. DISCUSSION: In this sample, we found neither a higher prevalence of latent toxoplasmosis in the AD group compared with the control group nor differences in serum anti-T. gondii IgG titers between groups.

No association between latent toxoplasmosis and multiple body measures in U.S. adults.

Toxoplasma gondii (Nicolle et Manceaux, 1908) is an intracellular parasite that can cause ongoing latent infection persisting for the duration of a non-definitive host's life. Affecting approximately one-third of the world's population, latent toxoplasmosis has been associated with neuropsychological outcomes and a previous report suggested an association between latent toxoplasmosis and adult height. Given the large number of people with latent toxoplasmosis and its potential associations with human height, we sought to better understand the association between latent toxoplasmosis and human morphology by evaluating seropositivity for T. gondii and multiple body measures reported in the National Health and Nutrition Examination Survey III (NHANES III) and in the more recent continuous NHANES data sets from the United States Centers for Disease Control and Prevention for which data on T. gondii are available. In these analyses, latent toxoplasmosis was not associated with any of the body measures assessed in the NHANES datasets even after taking into account interactions between latent toxoplasmosis and testosterone suggesting that in these samples, latent toxoplasmosis is not associated with adult morphology including height.

No association between current depression and latent toxoplasmosis in adults.

Changes in behaviour and cognition have been associated with latent infection from the apicomplexan protozoan Toxoplasma gondii (Nicolle et Manceaux, 1908) in both animal and human studies. Further, neuropsychiatric disorders such as schizophrenia have also been associated with latent toxoplasmosis. Previously, we found no association between T. gondii immunoglobulin G antibody (IgG) seropositivity and depression in human adults between the ages of 20 and 39 years (n = 1 846) in a sample representative of the United States collected by the Centers for Disease Control as part of a National Health and Nutrition Examination Survey (NHANES) from three datasets collected between 1999-2004. In the present study, we used NHANES data collected between 2009 and 2012 that included subjects aged 20 to 80 years (n = 5 487) and used the Patient Health Questionnaire 9 (PHQ-9) to assess depression with the overall aim of testing the stability of the results of the prior study. In the current study, the seroprevalence of T. gondii was 13%. The percentage of subjects reporting clinical levels of depression assessed with the PHQ-9 was 8%. As before, we found no association between T. gondii IgG seroprevalence and depression (OR = 1.01, 95% CI = 0.81-1.25; p = 0.944) while controlling for sex, educational attainment, race-ethnicity, age, poverty-to-income ratio and cigarette smoking. We also found no positive associations between anti-T. gondii antibody titre and depression (OR = 1.00, 95% CI = 0.96-1.06; p = 0.868). Moreover, we found no association between T. gondii seroprevalence or antibody titre and suicidal ideation (seroprevalence: OR = 1.22, 95% CI = .85-1.75; p = 0.277, titre: OR = 1.05, 95% CI = 0.98-1.14; p = 0.177). Defining depression to also include subjects currently taking antidepressant medication even with non-elevated questionnaires did not find evidence of a positive association between latent toxoplasmosis and depression. In the present study, neither T. gondii seroprevalence nor anti-T. gondii antibody titre was positively associated with depression or suicidal ideation among subjects aged 20 to 80 years.

Right frontal pole cortical thickness and social competence in children with chronic traumatic brain injury: cognitive proficiency as a mediator.

OBJECTIVE: To examine the association between right frontal pole cortical thickness, social competence, and cognitive proficiency in children participants with a history of chronic traumatic brain injury (TBI). PARTICIPANTS: Twenty-three children (65% male; M age = 12.8 years, SD = 2.3 years) at least 1 year post-injury (M = 3.3 years, SD = 1.7 years) were evaluated with the Cognitive Proficiency Index (CPI) from the Wechsler Intelligence Scale for Children, 4th Edition, and their caregiver completed the Child Behavior Checklist. Social competence was evaluated with the Social Competence and Social Problems subscales from the Child Behavior Checklist. Right frontal pole cortical thickness was calculated via FreeSurfer from high-resolution 3-dimensional T1 magnetic resonance imaging scans. RESULTS: Direct effect of right frontal pole cortical thickness on social competence was significant (ß = 14.09, SE = 4.6, P < .01). Right frontal pole cortical thickness significantly predicted CPI (ß = 18.44, SE = 4.9, P < .05), and CPI significantly predicted social competence (ß = 0.503, SE = 0.17, P < .01). Findings were consistent with the hypothesized mediation model. CONCLUSIONS: The association between right frontal lobe cortical integrity and social competence in pediatric participants with chronic TBI may be mediated through cognitive proficiency.

Association between toxocariasis and cognitive function in young to middle-aged adults.

The ascarid nematodes Toxocara canis (Werner, 1782) and Toxocara cati (Schrank, 1788) may infect humans resulting in toxocariasis. A prior study associated species of Toxocara Stiles, 1905 with cognitive deficits in children. To determine if a similar association between toxocariasis and cognition exists in adults, we analysed a large dataset from the United States' Center for Disease Control's National Health and Nutrition Examination Survey. We used linear-regression and multivariate models to examine the association between toxocariasis as assessed by the presence of anti-Toxocara IgG antibodies and three measures of cognitive function - simple reaction time (SRT), symbol-digit substitution (SDS) and serial-digit learning (SDL) in 4 279 adults aged 21 to 59 years. Toxocara seroprevalence did not vary with age or blood-lead concentration but did vary with gender, ethnicity, educational attainment and poverty-to-income ratio. Controlling for gender, age, blood-lead concentration, educational attainment, ethnic background and the poverty-to-income ratio, we found that toxocariasis predicted worse performance on the SDS but not on the SRT or the SDL. Moreover, there were significant interactions between toxocariasis and age, gender and educational attainment. In conclusion, toxocariasis appears to be associated with decreased cognitive function. Interactions between toxocariasis and gender, age and educational attainment further suggest that certain groups may be more susceptible than others to the cognitive dysfunction associated with toxocariasis in adults.

Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults.

Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.

Psychiatric Disease as a Potential Risk Factor for Dementia: A Narrative Review.

Neurodegenerative disease is a major global health problem with 150 million people predicted to have dementia by 2050. Genetic factors, environmental factors, demographics, and some diseases have been associated with dementia. In addition to associations between diseases such as hypertension and cerebrovascular disease and dementia, emerging findings associate some psychiatric disorders with incident dementia. Because of the high and increasing global prevalence of dementia and the high worldwide prevalence of psychiatric disorders, the primary objective of this narrative review was to evaluate published findings that evaluate the association between bipolar disorder, depression, anxiety, post-traumatic stress disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, schizophrenia and other psychosis syndromes, and personality disorders and personality traits and incident dementia. Here, we highlight findings indicating possible associations between these psychiatric disorders and subsequent dementia and suggest that some psychiatric disorders may be risk factors for incident dementia. Further research, including more large longitudinal studies and additional meta-analyses, however, is needed to better characterize the associations between psychiatric disorders and incident dementia, to identify possible mechanisms for these putative associations, and to identify risk factors within psychiatric disorders that predispose some people with a psychiatric disorder but not others to subsequent dementia. Additional important questions concern how the treatment of psychiatric disorders might affect the risk of incident dementia.

Human Cytomegalovirus Infection and Neurocognitive and Neuropsychiatric Health.

A common infection, human cytomegalovirus (HCMV) has been associated with a variety of human diseases, including cardiovascular disease and possibly certain cancers. HCMV has also been associated with cognitive, psychiatric, and neurological conditions. Children with congenital or early-life HCMV are at risk for microcephaly, cerebral palsy, and sensorineural hearing loss, although in many cases sensorineural loss may resolve. In addition, HCMV can be associated with neurodevelopmental impairment, which may improve with time. In young, middle-aged, and older adults, HCMV has been adversely associated with cognitive function in some but not in all studies. Research has linked HCMV to Alzheimer's and vascular dementia, but again not all findings consistently support these associations. In addition, HCMV has been associated with depressive disorder, bipolar disorder, anxiety, and autism-spectrum disorder, although the available findings are likewise inconsistent. Given associations between HCMV and a variety of neurocognitive and neuropsychiatric disorders, additional research investigating reasons for the considerable inconsistencies in the currently available findings is needed. Additional meta-analyses and more longitudinal studies are needed as well. Research into the effects of antiviral medication on cognitive and neurological outcomes and continued efforts in vaccine development have potential to lower the neurocognitive, neuropsychiatric, and neurological burden of HCMV infection.

Helicobacter pylori, persistent infection burden and structural brain imaging markers.

Persistent infections, whether viral, bacterial or parasitic, including Helicobacter pylori infection, have been implicated in non-communicable diseases, including dementia and other neurodegenerative diseases. In this cross-sectional study, data on 635 cognitively normal participants from the UK Biobank study (2006-21, age range: 40-70 years) were used to examine whether H. pylori seropositivity (e.g. presence of antibodies), serointensities of five H. pylori antigens and a measure of total persistent infection burden were associated with selected brain volumetric structural MRI (total, white, grey matter, frontal grey matter (left/right), white matter hyperintensity as percent intracranial volume and bi-lateral sub-cortical volumes) and diffusion-weighted MRI measures (global and tract-specific bi-lateral fractional anisotropy and mean diffusivity), after an average 9-10 years of lag time. Persistent infection burden was calculated as a cumulative score of seropositivity for over 20 different pathogens. Multivariable-adjusted linear regression analyses were conducted, whereby selected potential confounders (all measures) and intracranial volume (sub-cortical volumes) were adjusted, with stratification by Alzheimer's disease polygenic risk score tertile when exposures were H. pylori antigen serointensities. Type I error was adjusted to 0.007. We report little evidence of an association between H. pylori seropositivity and persistent infection burden with various volumetric outcomes (P > 0.007, from multivariable regression models), unlike previously reported in past research. However, H. pylori antigen serointensities, particularly immunoglobulin G against the vacuolating cytotoxin A, GroEL and outer membrane protein antigens, were associated with poorer tract-specific white matter integrity (P < 0.007), with outer membrane protein serointensity linked to worse outcomes in cognition-related tracts such as the external capsule, the anterior limb of the internal capsule and the cingulum, specifically at low Alzheimer's disease polygenic risk. Vacuolating cytotoxin A serointensity was associated with greater white matter hyperintensity volume among individuals with mid-level Alzheimer's disease polygenic risk, while among individuals with the highest Alzheimer's disease polygenic risk, the urease serointensity was consistently associated with reduced bi-lateral caudate volumes and the vacuolating cytotoxin A serointensity was linked to reduced right putamen volume (P < 0.007). Outer membrane protein and urease were associated with larger sub-cortical volumes (e.g. left putamen and right nucleus accumbens) at middle Alzheimer's disease polygenic risk levels (P < 0.007). Our results shed light on the relationship between H. pylori seropositivity, H. pylori antigen levels and persistent infection burden with brain volumetric structural measures. These data are important given the links between infectious agents and neurodegenerative diseases, including Alzheimer's disease, and can be used for the development of drugs and preventive interventions that would reduce the burden of those diseases.

Association between Toxoplasma gondii Infection and Type-1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Type-1 diabetes, an autoimmune disease characterized by damage to pancreatic insulin-producing beta cells, is associated with adverse renal, retinal, cardiovascular, and cognitive outcomes, possibly including dementia. Moreover, the protozoal parasite Toxoplasma gondii has been associated with type-1 diabetes. To better characterize the association between type-1 diabetes and Toxoplasma gondii infection, we conducted a systematic review and meta-analysis of published studies that evaluated the relationship between type-1 diabetes and Toxoplasma gondii infection. A random-effects model based on nine primary studies (total number of participants = 2655) that met our inclusion criteria demonstrated a pooled odds ratio of 2.45 (95% confidence interval, 0.91-6.61). Removing one outlying study increased the pooled odds ratio to 3.38 (95% confidence interval, 2.09-5.48). These findings suggest that Toxoplasma gondii infection might be positively associated with type-1 diabetes, although more research is needed to better characterize this association. Additional research is required to determine whether changes in immune function due to type-1 diabetes increase the risk of infection with Toxoplasma gondii, infection with Toxoplasma gondii increases the risk of type-1 diabetes, or both processes occur.