Quantitative T2 mapping-based longitudinal assessment of brain injury and therapeutic rescue in the rat following acute organophosphate intoxication.

Acute intoxication with organophosphate (OP) cholinesterase inhibitors poses a significant public health risk. While currently approved medical countermeasures can improve survival rates, they often fail to prevent chronic neurological damage. Therefore, there is need to develop effective therapies and quantitative metrics for assessing OP-induced brain injury and its rescue by these therapies. In this study we used a rat model of acute intoxication with the OP, diisopropylfluorophosphate (DFP), to test the hypothesis that T2 measures obtained from brain magnetic resonance imaging (MRI) scans provide quantitative metrics of brain injury and therapeutic efficacy. Adult male Sprague Dawley rats were imaged on a 7T MRI scanner at 3, 7 and 28 days post-exposure to DFP or vehicle (VEH) with or without treatment with the standard of care antiseizure drug, midazolam (MDZ); a novel antiseizure medication, allopregnanolone (ALLO); or combination therapy with MDZ and ALLO (DUO). Our results show that mean T2 values in DFP-exposed animals were: (1) higher than VEH in all volumes of interest (VOIs) at day 3; (2) decreased with time; and (3) decreased in the thalamus at day 28. Treatment with ALLO or DUO, but not MDZ alone, significantly decreased mean T2 values relative to untreated DFP animals in the piriform cortex at day 3. On day 28, the DUO group showed the most favorable T2 characteristics. This study supports the utility of T2 mapping for longitudinally monitoring brain injury and highlights the therapeutic potential of ALLO as an adjunct therapy to mitigate chronic morbidity associated with acute OP intoxication.

Caregivers of People With Mild Cognitive Impairment and Dementia: Characterizing Social and Psychological Outcomes.

OBJECTIVE: Little is known about caregiving across the spectrum of cognitive impairment [mild cognitive impairment (MCI) to dementia] and how early life and sociocultural factors affect caregiver health. In this study, we characterized differences between caregivers of those with MCI versus those with dementia. METHODS: A total of 158 caregivers were enrolled in this cross-sectional study, most of whom were dementia caregivers (65%). Caregivers completed questionnaires on depressive symptoms, self-rated health (SRH), perceived burden and stress, as well as psychosocial and demographic measures. RESULTS: Caregivers of those with MCI reported fewer depressive symptoms and lower stress and burden compared with dementia caregivers. In adjusted analyses caregivers with greater stress reported more depressive symptoms. For SRH, at lower stress levels, having a sibling die before age 18 (ie, early life adversity) was associated with poorer SRH; at higher stress levels, having early life adversity was associated with better SRH. At lower burden levels, more live births were associated with worse SRH; at higher burden levels, more live births were associated with better SRH. CONCLUSIONS: Early life factors are relevant for caregivers of those with cognitive impairment and targeted prevention and early intervention may be helpful in alleviating caregiver burden and stress.

The Impact of Sociodemographic Disadvantage on Cognitive Outcomes in Children With Newly Diagnosed Seizures and Their Unaffected Siblings Over 36 Months.

BACKGROUND: Accumulating evidence indicates that children with newly diagnosed epilepsy have comorbidities including cognitive challenges. Research investigating comorbidities has focused on clinical epilepsy characteristics and neurobiological/genetic correlates. The role that sociodemographic disadvantage (SD) may play has received less attention. We investigated the role of SD in cognitive status in youth with newly diagnosed epilepsy over a follow-up of 36 months to determine the degree, extent, and duration of the role of disadvantage. METHODS: A total of 289 children (six to 16 years) within six weeks of their first seizure along with 167 siblings underwent comprehensive neuropsychological assessments (intelligence, language, memory, executive function, processing speed, and academic achievement) at baseline, 18 months later, and at 36 months from baseline. Baseline demographic information (race, caregivers education, household income, and parental marital status), clinical epilepsy characteristics (e.g., age of onset), and magnetic resonance imaging (MRI) and electroencephalographic (EEG) information was collected. RESULTS: An SD index was computed for each family and categorized into four groups by level of disadvantage. In children and siblings, the least disadvantaged group exhibited the highest Full-Scale IQ, neuropsychological factor scores, and academic performances, whereas the most disadvantaged showed the polar opposite with the worst performances across all tests. Findings remained stable and significant over 36 months. Linear regression analyses indicated that disadvantage was a more constant and stable predictor of cognitive and academic performance over time compared with clinical epilepsy characteristics and MRI/EEG abnormalities. CONCLUSIONS: This study indicates the strong association between SD and cognitive/academic performance in children with newly diagnosed epilepsy and their siblings is significant and predictive of three-year cognitive outcomes.

Inclusion of Vietnamese Americans: Opportunities to understand dementia disparities.

There is a dearth of research on cognitive aging and dementia in Asian Americans, particularly Vietnamese Americans, who are the fourth largest Asian subgroup in the United States. The National Institutes of Health is mandated to make certain that racially and ethnically diverse populations are included in clinical research. Despite the widespread recognition to ensure that research findings can be generalizable to all groups, there are no estimates of the prevalence or incidence of mild cognitive impairment and Alzheimer's disease and related dementias (ADRD) in Vietnamese Americans, nor do we understand ADRD risk and protective factors in this group. In this article, we posit that studying Vietnamese Americans contributes to a better understanding of ADRD in general and offers unique opportunities for elucidating life course and sociocultural factors that contribute to cognitive aging disparities. That is, the unique context of Vietnamese Americans may provide understanding in terms of within-group heterogeneity and key factors in ADRD and cognitive aging. Here, we provide a brief history of Vietnamese American immigration and describe the large but often ignored heterogeneity of Asian Americans in the United States, elucidate how early life adversity and stress might influence late-life cognitive aging, and provide a basis for the role of sociocultural and health factors in the study of Vietnamese cognitive aging disparities. Research with older Vietnamese Americans provides a unique and timely opportunity to more fully delineate the factors that contribute to ADRD disparities for all populations.

A Review of Sedentary Behavior Assessment in National Surveillance Systems.

BACKGROUND: Temporal changes in sedentary behavior patterns reflect the evolving nature of our built and social environments, particularly the expanding availability of electronic media. It is important to understand what types of sedentary behavior are assessed in national surveillance to determine whether, and to what extent, they reflect contemporary patterns. The aims of this review were to describe the characteristics of questionnaires used for national surveillance of sedentary behavior and to identify the types of sedentary behaviors being measured. METHOD: We reviewed questionnaires from national surveillance systems listed on the Global Observatory for Physical Activity (GoPA!) country cards to locate items on sedentary behavior. Questionnaire characteristics were categorized using the Taxonomy of Self-reported Sedentary Behavior Tools (TASST). The purpose and type of sedentary behaviors captured were classified using the Sedentary Behavior International Taxonomy (SIT). RESULTS: Overall, 346 surveillance systems were screened for eligibility, of which 93 were included in this review. Most questionnaires used a single-item direct measure of sitting time (n = 78, 84%). Work and domestic were the most frequently captured purposes of sedentary behavior, while television viewing and computer use were the most frequently captured types of behaviors. CONCLUSION: National surveillance systems should be periodically reviewed in response to evidence on contemporary behavior patterns in the population and the release of updated public health guidelines.

Exploring the feasibility of collecting multimodal multiperson assessment data via distance in families affected by fragile X syndrome.

INTRODUCTION: Telehealth is an important tool in helping to provide services for hard-to-reach populations. One population that might benefit from telehealth are individuals with fragile X syndrome (FXS). Although FXS is the leading inherited cause of intellectual disability, it is nonetheless a low incidence disorder. Individuals with FXS and their families are involved in research studies, clinical trials and receive interventions - many of which are only offered in a few locations in the United States and thus, not easily accessible to many families. The current project explored the feasibility of using telehealth procedures to collect multimodal behavioural and psychological assessment data from these families. METHODS: Participation in the current study involved online surveys, measures of physiological indices of stress, live interviews and observations of mother-child interactions conducted via distance videoconferencing using the family's own technology when possible. Across all modes of data collection, we obtained information regarding the feasibility of participating entirely via distance by documenting missing data as well as each mother's overall impression of participating via distance. RESULTS: Our telehealth procedures were successfully implemented across a wide range of technology platforms with limited difficulty, and we documented little missing data due to technology-related challenges. Perhaps most importantly, however, our sample of mothers reported high satisfaction with participating via distance. DISCUSSION: These findings suggest that a wide range of services and types of assessments may be amenable to telehealth procedures. Further, the findings have immediate applications as the field shifts towards telehealth due to the coronavirus disease 2019 (COVID-19) pandemic.

Assessment of Physician Knowledge, Attitudes, and Practice for Lyme Disease in a Low-Incidence State.

Lyme disease (LD), caused by the bacterium Borrelia burgdorferi, is transmitted to humans in California through the bite of infected blacklegged ticks (Ixodes pacificus). Overall, the incidence of LD in California is low: approximately 0.2 confirmed cases per 100,000 population. However, California's unique ecological diversity results in wide variation in local risk, including regions with local foci at elevated risk of human disease. The diagnosis of LD can be challenging in California because the prior probability of infection for individual patients is generally low. Combined with nonspecific symptoms and complicated laboratory testing, California physicians need a high level of awareness of LD in California to recognize and diagnose LD efficiently. This research addresses an under-studied area of physicians' knowledge and practice of the testing and treatment of LD in a low-incidence state. We assessed knowledge and practices related to LD diagnosis using an electronic survey distributed to physicians practicing in California through mixed sampling methods. Overall, responding physicians in California had a general awareness of Lyme disease and were knowledgeable regarding diagnosis and treatment. However, we found that physicians in California could benefit from further education to improve test-ordering practices, test interpretation, and awareness of California's disease ecology with elevated levels of focal endemicity, to improve recognition, diagnosis, and treatment of LD in California patients.

Vascular Burden Score Impacts Cognition Independent of Amyloid PET and MRI Measures of Alzheimer's Disease and Vascular Brain Injury.

BACKGROUND/OBJECTIVE: To determine the impact of vascular burden on rates of decline in episodic memory and executive function. We hypothesize that greater vascular burden will have an additive negative impact on cognition after accounting for baseline cognitive impairment, positron emission tomography (PET) amyloid burden, and magnetic resonance imaging (MRI) measures. METHODS: Individuals were followed an average of 5 years with serial cognitive assessments. Predictor variables include vascular burden score (VBS), quantitative brain MRI assessment, and amyloid imaging. Subjects consisted of 65 individuals, 53% of whom were male, aged 73.2±7.2 years on average with an average of 15.5±3.3 years of educational achievement. RESULTS: Baseline cognitive impairment was significantly associated poorer episodic memory (p < 0.0001), smaller hippocampal volume (p < 0.0001), smaller brain volume (p = 0.0026), and greater global Pittsburg Imaging Compound B (PiB) index (p = 0.0008). Greater amyloid burden was associated with greater decline in episodic memory over time (ß= -0.20±0.07, p < 0.005). VBS was significantly associated with the level of executive function performance (ß= -0.14±0.05, p < 0.005) and there was a significant negative interaction between VBS, cognitive impairment, and PiB index (ß= -0.065±0.03, p = 0.03). CONCLUSIONS: Our results find a significant influence of VBS independent of standard MRI measures and cerebral amyloid burden on executive function. In addition, VBS reduced the amount of cerebral amyloid burden needed to result in cognitive impairment. We conclude that the systemic effects of vascular disease as reflected by the VBS independently influence cognitive ability.

A multivariate cure model for left-censored and right-censored data with application to colorectal cancer screening patterns.

We develop a multivariate cure survival model to estimate lifetime patterns of colorectal cancer screening. Screening data cover long periods of time, with sparse observations for each person. Some events may occur before the study begins or after the study ends, so the data are both left-censored and right-censored, and some individuals are never screened (the 'cured' population). We propose a multivariate parametric cure model that can be used with left-censored and right-censored data. Our model allows for the estimation of the time to screening as well as the average number of times individuals will be screened. We calculate likelihood functions based on the observations for each subject using a distribution that accounts for within-subject correlation and estimate parameters using Markov chain Monte Carlo methods. We apply our methods to the estimation of lifetime colorectal cancer screening behavior in the SEER-Medicare data set. Copyright © 2016 John Wiley & Sons, Ltd.

Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.