Consistency of the Disposition Index in the Face of Diet Induced Insulin Resistance: Potential Role of FFA

Objective Insulin resistance induces hyperinsulinemic compensation, which in turn maintains almost a constant disposition index. However, the signal that gives rise to the hyperinsulinemic compensation for insulin resistance remains unknown. Methods In a dog model of obesity we examined the possibility that potential early-week changes in plasma FFA, glucose, or both could be part of a cascade of signals that lead to compensatory hyperinsulinemia induced by insulin resistance. Results Hypercaloric high fat feeding in dogs resulted in modest weight gain, and an increase in adipose tissue with no change in the non-adipose tissue size. To compensate for the drop in insulin sensitivity, there was a significant rise in plasma insulin, which can be attributed in part to a decrease in the metabolic clearance rate of insulin and increased insulin secretion. In this study we observed complete compensation for high fat diet induced insulin resistance as measured by the disposition index. The compensatory hyperinsulinemia was coupled with significant changes in plasma FFAs and no change in plasma glucose. Conclusions We postulate that early in the development of diet induced insulin resistance, a change in plasma FFAs may directly, through signaling at the level of β-cell, or indirectly, by decreasing hepatic insulin clearance, result in the observed hyperinsulinemic compensation

Traumatic brain injury alters neuropsychiatric symptomatology in all-cause dementia.

INTRODUCTION: Traumatic brain injury (TBI) may alter the course of neuropsychiatric symptom (NPS) onset during dementia development. The connection among TBI, NPS, and dementia progression is of increasing interest to researchers and clinicians. METHODS: Incidence of NPS was examined in participants with normal cognition who progressed to all-cause dementia based on whether TBI history was present (n = 130) or absent (n = 849). Survival analyses were used to examine NPS incidence across 7.6 ± 3.0 years of follow-up. RESULTS: Participants with TBI history had increased prevalence and incidence of apathy (44.7% vs 29.9%, P = .0062; HR DISCUSSION: History of TBI is associated with increased risk for and earlier onset of NPS in the trajectory of dementia development

Use of a Mobile App to Augment Psychotherapy in a Community Psychiatric Clinic: Feasibility and Fidelity Trial.

BACKGROUND: Even though 1 in 5 Americans experience some form of mental illness each year, 80% have been shown to discontinue psychotherapy prematurely. The traditional psychotherapy service delivery model, consisting of isolated clinical sessions, lacks the ability to keep patients engaged outside clinical sessions. Newer digital mental health platforms can address the clinical need for a robust tool that tracks mental well-being and improves engagement in patients with depressive symptoms. OBJECTIVE: The primary goals of this feasibility study were to (1) assess compliance among providers and their patients with a digital mental health platform protocol, and (2) examine the usability and fidelity of a mobile app through structured participant feedback. METHODS: A sample of 30 participants was recruited for a 5-week study from a community-based mental health clinic in Baltimore, Maryland, USA. Inclusion criteria were: aged 18 years or older, having access to a smartphone, and having at least mild-to-moderate depression and/or anxiety as measured by the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales, respectively. Eligible participants were randomized into one of two study arms: (1) the intervention arm or (2) the waitlist control arm. Participants in the intervention arm were asked to download the Rose app and were prompted to complete clinical assessments (PHQ-9 and GAD-7) every other week, daily mood and anxiety Likert scales, and daily journal entries. The participants in the waitlist arm served as controls for the study and completed the clinical assessments only. Both arms engaged in weekly psychotherapy sessions, with participant in-app input informing the psychotherapy process of the intervention arm, while those in the waitlist control arm continued their standard care. Outcomes of interest included adherence to completion of in-app assessments and usability of the Rose mobile app assessed through the modified Mobile Application Rating Scale. RESULTS: Over the study period, a sample of 30 participants used the Rose app 2834 times to complete clinical assessments. On average, 70% (21; 95% CI 61.14%-77.41%) of participants completed mood and anxiety daily check-ins and journal entries 5 days per week. Nearly all participants (29/30, 97%) completed all PHQ-9 and GAD-7 in-app scales during the study. Subjective impressions showed that 73% (22/30) of participants found the mobile app to be engaging and in line with their needs, and approximately 70% (21/30) of participants reported the app functionality and quality of information to be excellent. Additionally, more than two-thirds of the participants felt that their knowledge and awareness of depression and anxiety management improved through using the app. CONCLUSIONS: Steady compliance and high app ratings showcase the utility of the Rose mobile mental health app in augmenting the psychotherapy process for patients with mood disorders and improving mental health knowledge. Future studies are needed to further examine the impact of Rose on treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04200170; https://clinicaltrials.gov/ct2/show/NCT04200170

The effect of age of first exposure to competitive fighting on cognitive and other neuropsychiatric symptoms and brain volume.

It has long been established that fighting sports such as boxing and mixed martial arts can lead to head injury. Prior work from this group on the Professional Fighters Brain Health Study found that exposure to repetitive head impacts is associated with lower brain volumes and decreased processing speed in fighters. Current and previously licensed professional fighters were recruited, divided into active and retired cohorts, and matched with a control group that had no prior experience in sports with likely head trauma. This study examined the relationship between age of first exposure (AFE) to fighting sports and brain structure (MRI regional volume), cognitive performance (CNS Vital Signs, iComet C3), and clinical neuropsychiatric symptoms (PHQ-9, Barratt Impulsiveness Scale). Brain MRI data showed significant correlations between earlier AFE and smaller bilateral hippocampal and posterior corpus callosum volumes for both retired and active fighters. Earlier AFE in active fighters was correlated with decreased processing speed and decreased psychomotor speed. Retired fighters showed a correlation between earlier AFE and higher measures of depression and impulsivity. Overall, the results help to inform clinicians, governing bodies, parents, and athletes of the risks associated with beginning to compete in fighting sports at a young age

History of traumatic brain injury interferes with accurate diagnosis of Alzheimer\u27s dementia: a nation-wide case-control study.

Traumatic brain injury (TBI) and Alzheimer\u27s disease (AD) bear a complex relationship, potentially increasing risk of one another reciprocally. However, recent evidence suggests post-TBI dementia exists as a distinct neurodegenerative syndrome, confounding AD diagnostic accuracy in clinical settings. This investigation sought to evaluate TBI\u27s impact on the accuracy of clinician-diagnosed AD using gold standard neuropathological criteria. In this preliminary analysis, data were acquired from the National Alzheimer\u27s Coordinating Centre (NACC), which aggregates clinical and neuropathologic information from Alzheimer\u27s disease centres across the United States. Modified National Institute on Aging-Reagan criteria were applied to confirm AD by neuropathology. Among participants with clinician-diagnosed AD, TBI history was associated with misdiagnosis (false positives) (OR = 1.351 [95% CI: 1.091-1.674]

Effect of Weight Class on Regional Brain Volume, Cognition, and Other Neuropsychiatric Outcomes among Professional Fighters.

Traumatic brain injury (TBI) is a common source of functional impairment among athletes, military personnel, and the general population. Professional fighters in both boxing and mixed martial arts (MMA) are at particular risk for repetitive TBI and may provide valuable insight into both the pathophysiology of TBI and its consequences. Currently, effects of fighter weight class on brain volumetrics (regional and total) and functional outcomes are unknown. Fifty-three boxers and 103 MMA fighters participating in the Professional Fighters Brain Health Study (PRBHS) underwent volumetric magnetic resonance imaging (MRI) and neuropsychological testing. Fighters were divided into lightweight (≤139.9 lb), middleweight (140.0-178.5 lb), and heavyweight (\u3e178.5 lb). Compared with lightweight fighters, heavyweights displayed greater yearly reductions in regional brain volume (boxers: bilateral thalami; MMA: left thalamus, right putamen) and functional performance (boxers: processing speed, simple and choice reaction; MMA: Trails A and B tests). Lightweights suffered greater reductions in regional brain volume on a per-fight basis (boxers: left thalamus; MMA: right putamen). Heavyweight fighters bore greater yearly burden of regional brain volume and functional decrements, possibly related to differing fight dynamics and force of strikes in this division. Lightweights demonstrated greater volumetric decrements on a per-fight basis. Although more research is needed, greater per-fight decrements in lightweights may be related to practices of weight-cutting, which may increase vulnerability to neurodegeneration post-TBI. Observed decrements associated with weight class may result in progressive impairments in fighter performance, suggesting interventions mitigating the burden of TBI in professional fighters may both improve brain health and increase professional longevity

Consistency of the hyperbolic relationship (DI) between insulin sensitivity and insulin secretion.

<p>Solid black hyperbolic curve =  average DI value for week 0; black solid square  =  average DI for week 0; open square  =  average DI for week 2; black solid triangle  =  average DI for week 4; open triangle  =  average DI for week 6. The hyperbola represents the curve on which the animals would have to remain to maintain a constant DI (DI = AIRg.SI = constant) and it is calculated as extrapolation of the average DI for week 0 over a range of insulin sensitivities.</p

Weekly changes in body weight and body composition.

<p>(A) Body weight increased by week 2 and remained elevated throughout the six-week hypercaloric high-fat feeding period. (B) Visceral (white bar) and subcutaneous (black bar) adipose tissue calculated as area percent of total tissue. *P<.05 vs. week0; **P<.01 vs. week 0; ***P<.001 vs. week 0.</p

Weekly estimates of insulin sensitivity, insulin secretion and whole-body insulin clearance.

<p>(A) SI, (B) AIRg, and (C) MCR of insulin. *P<.05 vs. week 0; **P<.01 vs. week 0; ***P<.001 vs week 0.</p

Observed fasting plasma insulin, glucose and FFAs.

<p>Fasting levels of (A) insulin, (B) glucose, and (C) FFA before and after fat feeding. *P<.05 vs. week0; **P<.01 vs. week 0; ***P<.001 vs. week 0.</p