Registered replication report of the construct validity of the error-related negativity (ERN): A multi-site study of task-specific ERN correlations with internalizing and externalizing symptoms.

Intact cognitive control is critical for goal-directed behavior and is widely studied using the error-related negativity (ERN). A common assumption in such studies is that ERNs recorded during different experimental paradigms reflect the same construct or functionally equivalent processes and that ERN is functionally distinct from other error-monitoring event-related brain potentials (ERPs; error positivity [Pe]), other neurophysiological indices of cognitive control (N2), and even other theoretically unrelated indices (visual N1). The present registered report represents a replication-plus-extension study of the psychometric validity of cognitive control ERPs and evaluated the convergent and divergent validity of ERN, Pe, N2, and visual N1 recorded during flanker, Stroop, and Go/no-go tasks. Data from 182 participants were collected from two study sites, and ERP psychometric reliability and validity were evaluated. Findings supported replication of convergent and divergent validity of ERN, Pe, and ΔPe (error minus correct)-these ERPs correlated more with themselves across tasks than with other ERPs measured during the same task. Convergent validity of ΔERN across tasks was not replicated, despite high internal consistency. ERN strongly correlated with N2 at levels similar or higher than those in support of convergent validity for other ERPs, and the present study failed to provide evidence of divergent validity for ERN and Pe from N2 or N1. ERN and ΔERN were unrelated to internalizing or externalizing symptoms. Findings underscore the importance of considering the psychometric validity of ERPs, as it provides a foundation for interpreting and comparing ERPs across tasks and studies.

Trends in Screen Time Use Among Children During the COVID-19 Pandemic, July 2019 Through August 2021.

Importance: The COVID-19 pandemic led to widespread lockdowns and school closures that may have affected screen time among children. Although restrictions were strongest early in the pandemic, it is unclear how screen time changed as the pandemic progressed. Objective: To evaluate change in children's screen time from before the pandemic to during the pandemic, from July 2019 through August 2021. Design, Setting, and Participants: This is a longitudinal cohort study with repeated measures of screen time collected before the pandemic and during 2 pandemic periods. Children aged 4 to 12 years and their parent were enrolled in 3 pediatric cohorts across 3 states in the US participating in the Environmental Influences of Child Health Outcomes (ECHO) Program. Data analysis was performed from November 2021 to July 2022. Exposures: COVID-19 pandemic period: prepandemic (July 2019 to March 2020), pandemic period 1 (December 2020 to April 2021), and pandemic period 2 (May 2021 to August 2021). Main Outcomes and Measures: The primary outcomes were total, educational (not including remote school), and recreational screen time assessed via the ECHO Child Media Use questionnaire. Linear mixed-effects models were used for screen time adjusted for child's age, number of siblings, sex, race, ethnicity, and maternal education. Results: The cohort included 228 children (prepandemic mean [SD] age, 7.0 [2.7] years; 100 female [43.9%]) with screen time measured during the prepandemic period and at least once during the pandemic period. Prepandemic mean (SD) total screen time was 4.4 (3.9) hours per day and increased 1.75 hours per day (95% CI, 1.18-2.31 hours per day) in the first pandemic period and 1.11 hours per day (95% CI, 0.49-1.72 hours per day) in the second pandemic period, in adjusted models. Prepandemic mean (SD) recreational screen time was 4.0 (3.5) hours per day and increased 0.89 hours per day (95% CI, 0.39-1.39 hours per day) in the first pandemic period and 0.70 hours per day (95% CI, 0.16-1.25 hours per day) in the second pandemic period. Prepandemic mean (SD) educational screen time was 0.5 (1.2) hours per day (median [IQR], 0.0 [0.0-0.4] hours per day) and increased 0.93 hours per day (95% CI, 0.67-1.19 hours per day) in the first pandemic period and 0.46 hours per day (95% CI, 0.18-0.74 hours per day) in the second pandemic period. Conclusions and Relevance: These findings suggest that screen time among children increased during the COVID-19 pandemic and remained elevated even after many public health precautions were lifted. The long-term association of increased screen time during the COVID-19 pandemic with children's health needs to be determined.

Threat-induced alterations in cognition and associations with dysregulated behavior.

Previous literature suggests that threat disrupts cognitive control, especially for those prone to engaging in dysregulated behaviors (i.e., maladaptive attempts at regulating stress). However, this relationship is not well understood and has yet to be directly examined. The current study extends previous literature by examining the link between individual differences in dysregulation and threat-related alterations in neurocognitive and behavioral indicators of cognitive control. Using a diverse community sample (N = 143), we recorded participants' brain activity during a flanker task under conditions of predictable, unpredictable, and no threat-of-shock. Findings revealed a nuanced relationship, whereby predictable threat, relative to unpredictable threat, was associated with larger N2 to flankers, perhaps at the expense of a reduced later P3. We also found a relationship between proneness toward dysregulated behaviors and threat-induced alterations of cognitive control, with those higher in dysregulation showing reduced conflict P3 differentiation and accuracy interference during threat vs. no threat conditions. This research expands what is known about how threat can modulate cognition in everyday life and linked it to dysregulated behaviors with high societal burden.

Impact of the COVID-19 pandemic on children's sleep habits: an ECHO study.

BACKGROUND: Sleep in childhood is affected by behavioral, environmental, and parental factors. We propose that these factors were altered during the COVID-19 pandemic. This study investigates sleep habit changes during the pandemic in 528 children 4-12 years old in the US, leveraging data from the Environmental Influences on Child Health Outcomes (ECHO) Program. METHODS: Data collection occurred in July 2019-March 2020 (pre-pandemic) and two pandemic periods: December 2020-April 2021 and May-August 2021. Qualitative interviews were performed in 38 participants. RESULTS: We found no changes in sleep duration, but a shift to later sleep midpoint during the pandemic periods. There was an increase in latency at the first pandemic collection period but no increase in the frequency of bedtime resistance, and a reduced frequency of naps during the pandemic. Qualitative interviews revealed that parents prioritized routines to maintain sleep duration but were more flexible regarding timing. Children from racial/ethnic minoritized communities slept less at night, had later sleep midpoint, and napped more frequently across all collection periods, warranting in-depth investigation to examine and address root causes. CONCLUSIONS: The COVID-19 pandemic significantly impacted children sleep, but parental knowledge of the importance of sleep might have played a significant protective role. IMPACT: During the COVID-19 pandemic, US children changed their sleep habits, going to bed and waking up later, but their sleep duration did not change. Sleep latency was longer. Parental knowledge of sleep importance might have played a protective role. Regardless of data collection periods, children from racial/ethnic minoritized communities slept less and went to bed later. This is one of the first study on this topic in the US, including prospective pre-pandemic qualitative and quantitative data on sleep habits. Our findings highlight the pandemic long-term impact on childhood sleep. Results warrants further investigations on implications for overall childhood health.

Threat effects on cognitive systems: Testing links to aggression proneness.

The biobehavioral study of aggression has implications for expanding our understanding of transdiagnostic processes that increase risk for disinhibited behaviors. Toward this end, our study tested tenets from the process model of aggression (Verona & Bresin, 2015). First, we expected that the predictability of threat would differentially alter cognitive networks, including attentional alerting and executive control. Second, we examined the moderating effects of self- and informant reports of aggression on threat-related changes in cognitive functioning. Using event-related potential (ERP) measures of cognitive-attentional processes, 143 community individuals participated in a well-validated and translational threat manipulation (NPU) task (Schmitz & Grillon, 2012) while completing the Attention Network Test (Fan et al., 2002). Analyses revealed that relatively unpredictable threat quickened alerting-related reaction time, whereas predictable threat interfered with processing of flanker task stimuli. The results, however, failed to show reliable relationships between aggression proneness and threat-related cognitive alterations. The findings fit with a broader literature on cognitive and behavioral outputs of threat activation and provide fruitful avenues for better understanding threat-related aggression. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Threat effects on attention networks in individuals with a history of externalizing behaviors.

Research identifying the biobehavioral processes that link threat exposure to cognitive alterations can inform treatments designed to reduce perpetration of stress-induced aggression. The present study attempted to specify the effects of relatively predictable versus unpredictable threat on two attention networks, attentional alerting and executive control. In a sample of adults (n = 74, 35 % identifying as women, Mage = 32.85) with high rates of externalizing behaviors (e.g., substance use, criminal/legal system involvement, aggressivity), we measured event-related brain activity during an attention network test that manipulated cognitive systems activation under relatively unpredictable and predictable threat conditions. Results showed that threat exposure alters attentional alerting and executive control. The predictable threat condition, relative to unpredictable threat, increased visual alerting (N1 amplitude to alert vs. no alert cue conditions) and decreased attention to the task (P3 amplitude to subsequent task-relevant flankers, but these effects did not survive adjusting for multiple tests. In contrast, overall threat and unpredictable threat conditions were associated with faster response time to alert cue (versus no cue) and poorer conflict processing, operationalized as flanker N2 reductions and slower response time to incongruent (versus congruent) flanker trials. These results expand what is known about threat-related modulation of cognition in a sample of individuals with histories of externalizing behaviors.

Health Behavior Changes during the COVID-19 Pandemic: A Longitudinal Analysis among Children.

This longitudinal study compared children's health behaviors before the COVID-19 pandemic versus during the pandemic. This analysis examined the association between individual-level characteristics and health behavior change. Four prospective cohort studies in the Environmental influences on Child Health Outcomes (ECHO) Program contributed data. Children aged 4−12 years and their caregivers were recruited in California, Colorado, North Dakota, and New Hampshire. Dietary intake, physical activity, screen time, and sleep duration were assessed with questionnaires pre-pandemic and during the pandemic. The final sample included 347 children: 47% female and 62% non-Hispanic White. Compared with pre-pandemic, weekday screen time duration was higher during the pandemic (3.0 vs. 4.5 h, p < 0.001). Unadjusted increases in screen time duration differed by race and ethnicity: 1.3 h/day for non-Hispanic White children, 2.3 h/day for Hispanic children, and 5.3 h/day for non-Hispanic Black children. Overall, no changes occurred in sugar-sweetened beverage (SSB) intake (p = 0.26), discretionary food intake (p = 0.93), and physical activity (p = 0.15). Sleep duration increased by 30 min among children who did not meet sleep recommendations pre-pandemic. Child sex and maternal education level were not associated with health behavior change. The pandemic may have exacerbated disparities in some health behaviors. Families may need support to re-establish healthy routines.

Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [18F]FPEB PET.

OBJECTIVE: Metabotropic glutamate receptor subtype 5 (mGluR5) is integral to the brain glutamatergic system and cognitive function. This study investigated whether aging is associated with decreased brain mGluR5 availability. METHODS: Cognitively normal participants (n = 45), aged 18 to 84 years, underwent [18F]FPEB positron emission tomography scans to quantify brain mGluR5. Distribution volume (VT) was computed using a venous or arterial input function and equilibrium modeling from 90 to 120 min. In the primary analysis, the association between age and VT in the hippocampus and association cortex was evaluated using a linear mixed model. Exploratory analyses assessed the association between age and VT in multiple brain regions. The contribution of gray matter tissue alterations and partial volume effects to associations with age was also examined. RESULTS: In the primary analysis, older age was associated with lower [18F]FPEB binding to mGluR5 (P = 0.026), whereas this association was not significant after gray matter masking or partial volume correction to account for age-related tissue loss. Post hoc analyses revealed an age-related decline in mGluR5 availability in the hippocampus of 4.5% per decade (P = 0.007) and a non-significant trend in the association cortex (P = 0.085). An exploratory analysis of multiple brain regions revealed broader inverse associations of age with mGluR5 availability, but not after partial volume correction. CONCLUSION: Reductions in mGluR5 availability with age appear to be largely mediated by tissue loss. Quantification of [18F]FPEB binding to mGluR5 may expand our understanding of age-related molecular changes and the relationship with brain tissue loss.

Psychopathic traits, inhibition, and positive and negative emotion: Results from an emotional Go/No-Go task.

Difficulty stopping unwanted or inappropriate actions (i.e., inhibitory control) is implicated in antisocial behaviors, which are common in people high in psychopathic traits. Recent research indicates that, for those with antisocial personality, inhibitory control is impaired under negative emotional contexts; however, it is unclear whether this impairment extends to persons with psychopathic traits and to impairments under positive emotional contexts. Identifying some of these distinctions can point to therapeutics that target negative emotion specifically or emotion dysregulation broadly. We sought to identify unique relationships between distinct facets of psychopathy and inhibitory control in the context of positive, negative, and neutral stimuli. Using a community sample (N = 117), event-related potentials were recorded during an emotional-linguistic Go/No-Go task. Results indicated distinct cognition-emotion relationships for each psychopathy facet. Higher interpersonal facet scores related to reciprocal interference between cognition and emotion. Higher callous affect facet scores related to reduced inhibitory and emotional processing, except when stimuli were most engaging (emotional No-Go trials). Higher erratic lifestyle facet scores related to increased effort required to process both emotion and inhibition cues. Finally, higher antisocial facet scores related to poorer behavioral inhibition overall. This research challenges the theoretical accounts of psychopathy focused on specific deficits in negative emotion, such as fearlessness, while offering some support for theories related to attentional dysfunction. Results also highlight the importance of facet-level theorizing, as results varied by facet. This study may inform efforts to reduce disinhibited behaviors, particularly in emotional contexts, among those high in certain psychopathic traits.

Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer's disease: A tracer kinetic modeling study.

[11C]UCB-J PET for synaptic vesicle glycoprotein 2 A (SV2A) has been proposed as a suitable marker for synaptic density in Alzheimer's disease (AD). We compared [11C]UCB-J binding for synaptic density and [18F]FDG uptake for metabolism (correlated with neuronal activity) in 14 AD and 11 cognitively normal (CN) participants. We assessed both absolute and relative outcome measures in brain regions of interest, i.e., K1 or R1 for [11C]UCB-J perfusion, VT (volume of distribution) or DVR to cerebellum for [11C]UCB-J binding to SV2A; and Ki or KiR to cerebellum for [18F]FDG metabolism. [11C]UCB-J binding and [18F]FDG metabolism showed a similar magnitude of reduction in the medial temporal lobe of AD -compared to CN participants. However, the magnitude of reduction of [11C]UCB-J binding in neocortical regions was less than that observed with [18F]FDG metabolism. Inter-tracer correlations were also higher in the medial temporal regions between synaptic density and metabolism, with lower correlations in neocortical regions. [11C]UCB-J perfusion showed a similar pattern to [18F]FDG metabolism, with high inter-tracer regional correlations. In summary, we conducted the first in vivo PET imaging of synaptic density and metabolism in the same AD participants and reported a concordant reduction in medial temporal regions but a discordant reduction in neocortical regions.

Electrocortical Effects of Acetaminophen during Emotional Picture Viewing, Cognitive Control, and Negative Feedback.

Acetaminophen, the active ingredient in Tylenol, may have psychological effects, such as reducing social and emotional pain. The current study (N = 173) used electroencephalography (EEG) to extend past research on acetaminophen. Healthy undergraduate students (64.7% women, age M = 18.15, SD = 3.33) were randomly assigned to ingest 1,000 mg of acetaminophen or placebo before completing emotional picture viewing (n = 143), a flanker task (n = 69), and a probabilistic learning task (n = 143) while EEG was recorded. (Sample sizes used for the analyses of each task differ from the total N due to data loss.) We observed standard event-related potentials (ERPs), including emotion-modulated late positive potentials during picture viewing and feedback-related negativity during feedback on the probabilistic learning task. We also observed standard error-related and conflict-related ERPs in the flanker task but could not adequately assess acetaminophen's effect on flanker ERPs due to excessive data loss. Acetaminophen did not alter any of the ERPs, in contrast to predictions based on prior research. Exploratory analyses revealed that acetaminophen reduced the relationship between trait behavioral inhibition system sensitivity and emotion-modulated late positive potentials. Together these findings suggest that a standard dose of acetaminophen did not reliably alter neural indicators of emotional or feedback processing. Instead, preliminary findings from our study suggested that a more nuanced relationship may exist between acetaminophen and individual differences in emotional processing, although this latter finding calls for further replication.

Facets of externalizing psychopathology in relation to inhibitory control and error processing.

A prominent characteristic of externalizing psychopathology is the inability to suppress or modulate behavioral responses and impulses. These tendencies have been associated with cognitive indicators of inhibitory control (P3) and error processing (error-related negativity [ERN] and positivity [Pe]). However, the extent to which these trait-like components are characteristic of specific manifestations, or externalizing proneness more generally, remains unclear. Our study aimed to further contextualize externalizing behaviors by examining associations between distinct facets of externalizing symptoms and relevant behavioral phenotypes (substance use, aggression, pathological personality and internalizing symptoms) as well as electrophysiological and behavioral indices of inhibitory control (congruence and no-go P3, flanker interference, commission errors) and error processing (ERN and Pe, post-error slowing). Using a sample of community and jail dwelling offenders (N = 497), we used Confirmatory Factor Analyses to estimate a general externalizing factor (EXT), representing shared variance, and latent factors representing symptoms related to callous-aggression (CAL; conduct disorder and antisocial personality disorder) and alcohol and drug dependence (AD and DD). Additionally, a subset of participants (N = 89) had their brain activity recorded during a flanker task. Factor analyses supported general EXT and CAL factors; however, unique AD/DD overlapped highly with shared EXT, suggesting that DSM substance use symptoms in our study reflect more general problems with disconstraint/impulsivity rather than variance specific to substances. The general EXT was marked by behavioral correlates of impulsivity and negative affect, and laboratory task deficits in error monitoring, but with greater differential processing of inhibitory cues. The CAL specific factor was associated with affective shallowness phenotype, and, interestingly, laboratory measures of enhanced processing of inhibitory cues and error adjustment. This research has implications for understanding neurocognitive processes associated with distinct manifestations of disordered behavioral inhibition.

Evaluation of a Vaccine-Communication Tool for Physicians.

OBJECTIVES: To evaluate a Kaiser Permanente Northern California physician training tool entitled "Effective Communication without Confrontation" aimed at improving communication with vaccine-hesitant parents, building trust, and alleviating physician stress surrounding vaccination visits. STUDY DESIGN: Trainings were held May to July 2015. Pre- and post-training surveys assessed physician comfort and perceived effectiveness in communicating with vaccine-hesitant parents. We measured vaccination coverage at the 2-, 4-, and 6-month well-child visits, and days undervaccinated at 9 months of age. We compared vaccination rates before and after the training. RESULTS: Of 415 physicians who received training, 249 completed post-training surveys. Physicians reported that the training helped them feel "much more or more" comfortable talking with parents who are unsure (72.3%), want to delay (73.9%), or refuse (63.5%) vaccinations and "much more or more" effective at persuading parents who are unsure (67.5%) or want to delay vaccinations (61.4%). They reported feeling "the same or less" effective persuading parents who refuse vaccinations (66.3%). Vaccine coverage remained unchanged and high from before to after the training (95%-96%), as did parent satisfaction with his or her child's provider (4.73/5.00). CONCLUSIONS: The Effective Communication without Confrontation training did not increase vaccine coverage, but did improve physicians' comfort and perceived effectiveness communicating with most vaccine-hesitant parents and may help to ease potentially stressful vaccination visits.

Comparative Effectiveness of 2 Diabetes Prevention Lifestyle Programs in the Workplace: The City and County of San Francisco Diabetes Prevention Trial.

INTRODUCTION: Data on the comparative effectiveness of Diabetes Prevention Programs (DPPs) in the workplace are limited. METHODS: Between September 2015 and July 2016, employees of the City and County of San Francisco who were at risk for type 2 diabetes (N = 158) were randomly assigned to one of 2 DPP-derived programs recognized by the Centers for Disease Control and Prevention: an in-person YMCA-DPP (n = 78) or an online virtual lifestyle management DPP (VLM-DPP) offered through Canary Health (n = 80). The primary outcome was change in body weight assessed at 6 and 12 months. Follow-up ended in August 2017. RESULTS: Both the YMCA-DPP and VLM-DPP yielded a significant reduction in percentage body weight at 6 months. For the YMCA-DPP, mean percentage change at 6 months was -2.70% (95% confidence interval [CI], -3.91% to -1.48%) and at 12 months was -2.46% (95% CI, -4.24% to -0.68%). For the VLM-DPP, mean percentage change at 6 months was -2.41% (95% CI, -4.07% to -0.77%) and at 12 months was -1.59% (95% CI, -3.51% to 0.33%). The mean between-condition difference at 6 months was -0.25% (95% CI, -2.04% to 1.55%) and at 12 months was -0.84% (95% CI, -3.03% to 1.34%). No significant differences were observed between conditions. The YMCA-DPP had a slightly higher reduction in waist circumference than VLM-DDP at 6 months (mean between-condition difference -2.00 cm [95% CI, -4.24 to 0.25 cm]). Participant engagement, expressed as mean number of completed core program sessions, was significantly higher for the YMCA-DPP than the VLM-DPP. Participants of the YMCA-DPP completed an average of 10.2 sessions (95% CI, 9.0 to 11.4), and participants of the VLM-DPP completed an average of 5.9 sessions (95% CI, 4.7 to 7.1). The adjusted mean between-condition difference was 4.2 sessions (95% CI, 2.54 to 5.99). CONCLUSION: Both the YMCA-DPP and VLM-DPP yielded weight loss at 6 months, which was maintained at 12 months in the YMCA-DPP. The workplace may be an effective setting to offer DPPs.

PET imaging of mGluR5 in Alzheimer's disease.

BACKGROUND: Metabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer's disease (AD) by mediating the synaptotoxic action of amyloid-ß oligomers. We utilized the positron emission tomography (PET) radioligand [18F]FPEB to investigate mGluR5 binding in early AD. METHODS: Sixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid. Diagnostic groups were well balanced for age, sex, and education. Dynamic PET scans were acquired for 60 min, starting at 60 min after the initial administration of up to 185 MBq of [18F]FPEB using a bolus-plus-constant-infusion method (Kbol = 190 min). Equilibrium modeling with a cerebellum reference region was used to estimate [18F]FPEB binding (BPND) to mGluR5. Analyses were performed with and without corrections for gray matter atrophy and partial volume effects. RESULTS: Linear mixed model analysis demonstrated a significant effect of group (p = 0.011) and the group × region interaction (p = 0.0049) on BPND. Post hoc comparisons revealed a significant reduction (43%) in mGluR5 binding in the hippocampus of AD (BPND = 0.76 ± 0.41) compared to CN (BPND = 1.34 ± 0.58, p = 0.003, unpaired t test) participants, and a nonsignificant trend for a reduction in a composite association cortical region in AD (BPND = 1.57 ± 0.25) compared to CN (BPND = 1.86 ± 0.63, p = 0.093) participants. Exploratory analyses suggested additional mGluR5 reductions in the entorhinal cortex and parahippocampal gyrus in the AD group. In the overall sample, hippocampal mGluR5 binding was associated with episodic memory scores and global function. CONCLUSIONS: [18F]FPEB-PET revealed reductions in hippocampal mGluR5 binding in early AD. Quantification of mGluR5 binding in AD may expand our understanding of AD pathogenesis and accelerate the development of novel biomarkers and treatments.

Statin Use and Risk of Cognitive Decline in the ADNI Cohort.

OBJECTIVE: To investigate associations between statin use and cognitive change, as well as diagnostic conversion, in individuals with cognitively normal (CN) status, mild cognitive impairment (MCI), and dementia due to Alzheimer disease (AD-dementia). METHODS: A multicenter cohort study with 1629 adults 48 to 91 years old with CN status, early MCI (EMCI), late MCI (LMCI), or AD-dementia at baseline followed prospectively for 24 months. Statin use was assessed at baseline, and cognition was measured over time with a composite memory score, a composite executive function score, and a global cognition score (Alzheimer's Disease Assessment Scale). Conversion to a more impaired diagnostic category was determined by clinician assessment. Repeated measures linear mixed-effects models were used to evaluate associations between statin use and change in cognition over time. Cox proportional hazards models were used to evaluate associations between statin use and time to diagnostic conversion. All models were stratified by baseline diagnostic group. RESULTS: Statin use was not associated with change in cognitive measures for CN, LMCI, or AD-dementia participants. Among EMCI participants, statin use was associated with a significantly slower rate of decline on the memory composite, but no other cognitive measure. Statin use was not associated with time to conversion for any diagnostic group. CONCLUSIONS: This study did not support an association between statin use and diagnostic conversion but suggested a possible association between statin use and cognitive change in EMCI. Additional randomized clinical trials of statins may be warranted in the prodromal EMCI stage of AD.

Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging.

Importance: Synaptic loss is well established as the major structural correlate of cognitive impairment in Alzheimer disease (AD). The ability to measure synaptic density in vivo could accelerate the development of disease-modifying treatments for AD. Synaptic vesicle glycoprotein 2A is an essential vesicle membrane protein expressed in virtually all synapses and could serve as a suitable target for synaptic density. Objective: To compare hippocampal synaptic vesicle glycoprotein 2A (SV2A) binding in participants with AD and cognitively normal participants using positron emission tomographic (PET) imaging. Design, Setting, and Participants: This cross-sectional study recruited 10 participants with AD and 11 participants who were cognitively normal between November 2015 and June 2017. We hypothesized a reduction in hippocampal SV2A binding in AD, based on the early degeneration of entorhinal cortical cell projections to the hippocampus (via the perforant path) and hippocampal SV2A reductions that had been observed in postmortem studies. Participants underwent high-resolution PET scanning with ((R)-1-((3-(11C-methyl-11C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one), a compound more commonly known as 11C-UCB-J, for SV2A. They also underwent high-resolution PET scanning with carbon 11-labeled Pittsburgh Compound B (11C-PiB) for ß-amyloid, magnetic resonance imaging, and cognitive and neurologic evaluation. Main Outcomes and Measures: Outcomes were 11C-UCB-J-specific binding (binding potential [BPND]) via PET imaging in brain regions of interest in participants with AD and participants who were cognitively normal. Results: Ten participants with AD (5 male and 5 female; mean [SD] age, 72.7 [6.3] years; 10 [100%] ß-amyloid positive) were compared with 11 participants who were cognitively normal (5 male and 6 female; mean [SD] age, 72.9 [8.7] years; 11 [100%] ß-amyloid negative). Participants with AD spanned the disease stages from amnestic mild cognitive impairment (n = 5) to mild dementia (n = 5). Participants with AD had significant reduction in hippocampal SV2A specific binding (41%) compared with cognitively normal participants, as assessed by 11C-UCB-J-PET BPND (cognitively normal participants: mean [SD] BPND, 1.47 [0.37]; participants with AD: 0.87 [0.50]; P = .005). These reductions remained significant after correction for atrophy (ie, partial volume correction; participants who were cognitively normal: mean [SD], 2.71 [0.46]; participants with AD: 2.15 [0.55]; P = .02). Hippocampal SV2A-specific binding BPND was correlated with a composite episodic memory score in the overall sample (R = 0.56; P = .01). Conclusions and Relevance: To our knowledge, this is the first study to investigate synaptic density in vivo in AD using 11C-UCB-J-PET imaging. This approach may provide a direct measure of synaptic density, and it therefore holds promise as an in vivo biomarker for AD and as an outcome measure for trials of disease-modifying therapies, particularly those targeted at the preservation and restoration of synapses.

Sleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort.

BACKGROUND: We investigated the relationship between sleep disturbance and cognitive decline or clinical conversion in individuals with normal cognition (CN), as well as those with mild cognitive impairment (MCI) and dementia due to Alzheimer disease (AD-dementia). METHODS: Secondary analysis of 1,629 adults between 48 and 91 years of age with up to 24 months of follow-up from the ADNI (Alzheimer's Disease Neuroimaging Initiative), a longitudinal cohort study. RESULTS: Sleep disturbance was not associated with decline in memory, executive function, or global cognition. The presence of sleep disturbance did not significantly increase the risk of diagnostic conversion in CN, early MCI, or late MCI participants. CONCLUSION: This study investigated the effect of sleep disturbance on cognitive decline using several outcomes and does not support the hypothesis that sleep disturbance predicts subsequent cognitive decline.

Risk factors and familial clustering for fever 7-10days after the first dose of measles vaccines.

BACKGROUND: Seven to ten days after a first dose of a measles-containing vaccine (MCV; i.e., MMR or MMRV), children have elevated fever risk which can be associated with febrile seizures. This study investigated individual and familial factors associated with fever 7-10days after MCV. METHODS: Retrospective cohort study among children who were <36months of age at receipt of MCV in six sites of the Vaccine Safety Datalink from 1/1/2000 to 12/31/2012. We evaluated medically-attended clinic or emergency department visits with a code for fever 7-10days after any MCV ("MCV- associated"). We evaluated factors associated with MCV-associated fever using χ2 and multivariable logistic regression analyses. RESULTS: Among 946,806 children vaccinated with MCV, we identified 7480 (0.8%) MCV-associated fever visits. Compared with children without fever after MCV, children with MCV-associated fever were more likely to have received MMRV than MMR (OR 1.3 95% CI 1.2, 1.5), have had medically attended fever both following previous vaccines (OR 1.3 95% CI 1.1, 1.6) and at any other previous time (OR 1.7 95% CI 1.6, 1.8), have had at least 1 prior seizure (OR 2.2 95% CI 1.7, 2.7), and have had >3 medical visits within the 6months before MCV (OR 1.7 95% CI 1.6, 1.8). In families with multiple MCV-immunized children, after adjusting for healthcare seeking behavior care for fever, those whose siblings had MCV-associated fever were more likely to also have MCV-associated fever (OR 3.5 95% CI 2.5, 4.8). DISCUSSION: Children who received MMRV vaccine or who had prior medically-attended fevers and seizures during the first year of life had increased risk of fever after a first dose of measles vaccine. After adjusting for familial propensity to seek care, MCV-associated fever still clustered within families, suggesting a possible genetic basis for susceptibility to developing fever due to measles vaccines.

Randomized trial of a prevention intervention that embeds weight-related messages within a general parenting program.

OBJECTIVE: To assess the extent to which an obesity prevention intervention that embeds obesity-related messages within a parenting program, compared with controls who received weekly mailings, resulted in a smaller increase in children's BMI (primary outcome) and improvements in weight-related behaviors from baseline to 9-month follow-up. METHODS: Fifty-six families were randomly assigned to the intervention and 56 to control. Children were primarily Hispanic (58%) or Black/African American (23%). Intervention included nine weekly: group parenting sessions, children's sessions, and homework assignments. At baseline, post-intervention, and 9-month follow-up, staff assessed children's weight and height. Parents completed surveys assessing parenting skills, feeding behaviors, and children's weight-related behaviors. RESULTS: From baseline to 9-month follow-up, BMI decreased by a mean of 0.13 kg m(-2) among children in the intervention and increased by 0.21 kg m(-2) among children in the control, resulting in a nonsignificant difference (multivariate adjusted difference = -0.36; 95% confidence interval [CI] -1.23, 0.51; P = 0.41). Parents in the intervention decreased restrictive feeding practices relative to control (-0.30; 95% CI -0.53, -0.07; P = 0.01). Intervention and control arms showed similar changes in children's weight-related behaviors. CONCLUSIONS: The intervention improved restrictive feeding but did not influence children's BMI or weight-related behaviors compared to controls who received weekly mailings.