Protocol for a prospective, randomized, controlled trial of Mental Contrasting with Implementation Intentions (MCII) to enhance the effectiveness of VA's MOVE! weight management program: WOOP (Wish, Outcome, Obstacle, Plan) VA.

INTRODUCTION: Intensive weight management programs are effective but often have low enrollment and high attrition. Lack of motivation is a key psychological barrier to enrollment, engagement, and weight loss. Mental Contrasting with Implementation Intentions (MCII) is a unique imagery technique that increases motivation for behavior change. We describe our study protocol to assess the efficacy and implementation of MCII to enhance the effectiveness of VA's MOVE! or TeleMOVE! weight management programs using a procedure called "WOOP" (Wish, Outcome, Obstacle, Plan) for Veterans. We hypothesize that WOOP+MOVE! or TeleMOVE! (intervention) will lead to greater MOVE!/TeleMOVE! program engagment and consequently weight loss than MOVE!/TeleMOVE! alone (control). METHOD: Veterans are randomized to either the intervention or control. Both arms receive the either MOVE! or TeleMOVE! weight management programs. The intervention group receives an hour long WOOP training while the control group receives patient education. Both groups receive telephone follow up calls at 3 days, 4 weeks, and 2 months post-baseline. Eligible participants are Veterans (ages 18-70 years) with either obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 25 kg/m2) and an obesity-associated co-morbidity. At baseline, 6 and 12 months, we assess weight, diet, physical activity in both groups. The primary outcome is mean percent weight change at 6 months. Secondary outcomes include changes in waist circumference, diet, physical activity, and dieting self-efficacy and engagement in regular physical activity. We assess implementation using the RE-AIM framework. CONCLUSION: If WOOP VA is found to be efficacious, it will be an important tool to facilitate weight management and improve weight outcomes. CLINICAL TRIAL REGISTRATION: NCT05014984.

Effectiveness of Goal-Directed and Outcome-Based Financial Incentives for Weight Loss in Primary Care Patients With Obesity Living in Socioeconomically Disadvantaged Neighborhoods: A Randomized Clinical Trial.

Importance: Financial incentives for weight management may increase use of evidence-based strategies while addressing obesity-related economic disparities in low-income populations. Objective: To examine the effects of 2 financial incentive strategies developed using behavioral economic theory when added to provision of weight management resources. Design, Setting, and Participants: Three-group, randomized clinical trial conducted from November 2017 to May 2021 at 3 hospital-based clinics in New York City, New York, and Los Angeles, California. A total of 1280 adults with obesity living in low-income neighborhoods were invited to participate, and 668 were enrolled. Interventions: Participants were randomly assigned to goal-directed incentives, outcome-based incentives, or a resources-only group. The resources-only group participants were given a 1-year commercial weight-loss program membership, self-monitoring tools (digital scale, food journal, and physical activity monitor), health education, and monthly one-on-one check-in visits. The goal-directed group included resources and linked financial incentives to evidence-based weight-loss behaviors. The outcome-based arm included resources and linked financial incentives to percentage of weight loss. Participants in the incentive groups could earn up to $750. Main Outcomes and Measures: Proportion of patients achieving 5% or greater weight loss at 6 months. Results: The mean (SD) age of the 668 participants enrolled was 47.7 (12.4) years; 541 (81.0%) were women, 485 (72.6%) were Hispanic, and 99 (14.8%) were Black. The mean (SD) weight at enrollment was 98.96 (20.54) kg, and the mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 37.95 (6.55). At 6 months, the adjusted proportion of patients who lost at least 5% of baseline weight was 22.1% in the resources-only group, 39.0% in the goal-directed group, and 49.1% in the outcome-based incentive group (difference, 10.08 percentage points [95% CI, 1.31-18.85] for outcome based vs goal directed; difference, 27.03 percentage points [95% CI, 18.20-35.86] and 16.95 percentage points [95% CI, 8.18-25.72] for outcome based or goal directed vs resources only, respectively). However, mean percentage of weight loss was similar in the incentive arms. Mean earned incentives was $440.44 in the goal-directed group and $303.56 in the outcome-based group, but incentives did not improve financial well-being. Conclusions and Relevance: In this randomized clinical trial, outcome-based and goal-directed financial incentives were similarly effective, and both strategies were more effective than providing resources only for clinically significant weight loss in low-income populations with obesity. Future studies should evaluate cost-effectiveness and long-term outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03157713.

Peer-Assisted Lifestyle (PAL) intervention: a protocol of a cluster-randomised controlled trial of a health-coaching intervention delivered by veteran peers to improve obesity treatment in primary care.

INTRODUCTION: Among US veterans, more than 78% have a body mass index (BMI) in the overweight (≥25 kg/m2) or obese range (≥30 kg/m2). Clinical guidelines recommend multicomponent lifestyle programmes to promote modest, clinically significant body mass (BM) loss. Primary care providers (PCPs) often lack time to counsel and refer patients to intensive programmes (≥6 sessions over 3 months). Using peer coaches to deliver obesity counselling in primary care may increase patient motivation, promote behavioural change and address the specific needs of veterans. We describe the rationale and design of a cluster-randomised controlled trial to test the efficacy of the Peer-Assisted Lifestyle (PAL) intervention compared with enhanced usual care (EUC) to improve BM loss, clinical and behavioural outcomes (aim 1); identify BM-loss predictors (aim 2); and increase PCP counselling (aim 3). METHODS AND ANALYSIS: We are recruiting 461 veterans aged 18-69 years with obesity or overweight with an obesity-associated condition under the care of a PCP at the Brooklyn campus of the Veterans Affairs NY Harbor Healthcare System. To deliver counselling, PAL uses in-person and telephone-based peer support, a tablet-delivered goal-setting tool and PCP training. Patients in the EUC arm receive non-tailored healthy living handouts. In-person data collection occurs at baseline, month 6 and month 12 for patients in both arms. Repeated measures modelling based on mixed models will compare mean BM loss (primary outcome) between study arms. ETHICS AND DISSEMINATION: The protocol has been approved by the Institutional Review Board and the Research and Development Committee at the VA NY Harbor Health Systems (#01607). We will disseminate the results via peer-reviewed publications, conference presentations and meetings with stakeholders. TRIAL REGISTRATION NUMBER: NCT03163264; Pre-results.

Protocol for a cluster-randomized controlled trial of a technology-assisted health coaching intervention for weight management in primary care: The GEM (goals for eating and moving) study.

INTRODUCTION: Over one-third of American adults have obesity with increased risk of chronic disease. Primary care providers often do not counsel patients about weight management due to barriers such as lack of time and training. To address this problem, we developed a technology-assisted health coaching intervention called Goals for Eating and Moving (GEM) to facilitate obesity counseling within the patient-centered medical home (PCMH) model of primary care. The objective of this paper is to describe the rationale and design of a cluster-randomized controlled trial to test the GEM intervention when compared to Enhanced Usual Care (EUC). METHOD: We have randomized 19 PCMH teams from two NYC healthcare systems (VA New York Harbor Healthcare System and Montefiore Medical Group practices) to either the GEM intervention or EUC. Eligible participants are English and Spanish-speaking primary care patients (ages 18-69 years) with obesity or who are overweight with comorbidity (e.g., arthritis, sleep apnea, hypertension). The GEM intervention consists of a tablet-delivered goal setting tool, a health coaching visit and twelve telephone calls for patients, and provider counseling training. Patients in the EUC arm receive health education materials. The primary outcome is mean weight loss at 1 year. Secondary outcomes include changes in waist circumference, diet, and physical activity. We will also examine the impact of GEM on obesity-related provider counseling competency and attitudes. CONCLUSION: If GEM is found to be efficacious, it could provide a structured approach for improving weight management for diverse primary care patient populations with elevated cardiovascular disease risk.

Goal-directed versus outcome-based financial incentives for weight loss among low-income patients with obesity: rationale and design of the Financial Incentives foR Weight Reduction (FIReWoRk) randomised controlled trial.

INTRODUCTION: Obesity is a major public health challenge and exacerbates economic disparities through employment discrimination and increased personal health expenditures. Financial incentives for weight management may intensify individuals' utilisation of evidence-based behavioural strategies while addressing obesity-related economic disparities in low-income populations. Trials have focused on testing incentives contingent on achieving weight loss outcomes. However, based on social cognitive and self-determination theories, providing incentives for achieving intermediate behavioural goals may be more sustainable than incentivising outcomes if they enhance an individual's skills and self-efficacy for maintaining long-term weight loss. The objective of this paper is to describe the rationale and design of the Financial Incentives foR Weight Reduction study, a randomised controlled trial to test the comparative effectiveness and cost-effectiveness of two financial incentive strategies for weight loss (goal directed vs outcome based) among low-income adults with obesity, as well as compared with the provision of health behaviour change resources alone. METHODS AND ANALYSIS: We are recruiting 795 adults, aged 18-70 years with a body mass index ≥30 kg/m2, from three primary care clinics serving residents of socioeconomically disadvantaged neighbourhoods in New York City and Los Angeles. All participants receive a 1-year commercial weight loss programme membership, self-monitoring tools (bathroom scale, food journal and Fitbit Alta HR), health education and monthly check-in visits. In addition to these resources, those in the two intervention groups can earn up to $750 over 6 months for: (1) participating in an intensive weight management programme, self-monitoring weight and diet and meeting physical activity guidelines (goal-directed arm); or (2) a ≥1.5% to ≥5% reduction in baseline weight (outcome-based arm). To maximise incentive efficacy, we incorporate concepts from behavioural economics, including immediacy of payments and framing feedback to elicit regret aversion. We will use generalised mixed effect models for repeated measures to examine intervention effects on weight at 6, 9 and 12 months. ETHICS AND DISSEMINATION: Human research protection committees at New York University School of Medicine, University of California Los Angeles (UCLA) David Geffen School of Medicine and Olive-View-UCLA Medical Center granted ethics approval. We will disseminate the results of this research via peer-reviewed publications, conference presentations and meetings with stakeholders. TRIAL REGISTRATION NUMBER: NCT03157713.

Cognitive functions among predominantly minority urban adolescents with metabolic syndrome.

The rise in the rate of adolescent obesity has led to a concurrent rise in the rate of metabolic syndrome (MetS) among young people. In addition to diabetes and cardiovascular disease, MetS has also been linked to cognitive dysfunction. The goal of this study was to assess whether cognitive differences exist between minority urban adolescents carrying excess weight who meet criteria for MetS as compared to their peers without MetS. Two hundred and ninety-six urban adolescents, predominantly Hispanic and carrying excess weight as defined by a BMI above 25 kg/m2, were screened for MetS and divided into MetS and no MetS groups. All participants completed the CNS Vital Signs (CNS-VS) computerized neurocognitive battery that assesses cognitive domains of Memory, Processing Speed, Reaction Time, Executive Function, Complex Attention, and Cognitive Flexibility. The MetS group (29.2%, n = 84) performed significantly lower on 2 of the 7 cognitive domains: Executive Function (EF) and Cognitive Flexibility. Additionally, waist circumference was determined to be a significant predictor of both these domains. These findings suggest EF is negatively impacted in adolescents with MetS, despite there being no statistical differences between MetS groups on most other measured cognitive domains. Due to the interrelated nature of obesity, waist circumference, and MetS, these findings have larger implications for the obesity epidemic as well.

Asian Adolescents with Excess Weight are at Higher Risk for Insulin Resistance than Non-Asian Peers.

OBJECTIVE: The purpose of this study was to evaluate whether Asian American adolescents have higher metabolic risk from excess weight than non-Asians. METHODS: Seven hundred thirty-three students, aged 14 to 19 years old, completed a school-based health screening. The 427 Asian and 306 non-Asian students were overall equivalent on age, sex, and family income. Height, weight, waist circumference, percent body fat, and blood pressure were measured. Fasting triglycerides, high- and low-density lipoproteins, glucose, and insulin levels were measured. Asian and non-Asians in lean or overweight/obesity groups were contrasted on the five factors that make up the metabolic syndrome. RESULTS: Asian adolescents carrying excess weight had significantly higher insulin resistance (IR), triglyceride levels, and waist-height ratios (W/H), despite a significantly lower overall BMI than corresponding non-Asians. Similarly, Asians had a stronger relationship between W/H and the degree of IR than non-Asian counterparts; 35% and 18% of the variances were explained (R2 = 0.35, R2 = 0.18) respectively, resulting in a significant W/H by racial group interaction (Fchange [1,236] = 11.56, P < 0.01). CONCLUSIONS: Despite lower overall BMI, Asians have higher IR and triglyceride levels from excess weight than their non-Asian counterparts. One-size-fits-all public health policies targeting youth should be reconsidered and attention paid to Asian adolescents, including those with mild degrees of excess weight.

Obese Adolescents Show Reduced Cognitive Processing Speed Compared with Healthy Weight Peers.

BACKGROUND: Childhood obesity and obesity-associated diabetes and metabolic syndrome (MetS) continue to rise. Obesity has been linked to structural and functional brain abnormalities, particularly in the frontal lobe. METHODS: One hundred sixty-two adolescents (aged 19.53 ± 1.53 years) underwent medical, neurocognitive, and brain magnetic resonance imaging assessments. Participants were either healthy weight (BMI <25.0 kg/m2 or BMI percentile <85%) or obese (BMI ≥30.0 kg/m2 or BMI percentile ≥95%). We evaluated frontal lobe cognitive functions and the size of the corpus callosum (CC). RESULTS: Groups differed on four measures of processing speed contained in four different cognitive tests, but not on executive function. A confirmatory factor analysis verified that the significant processing speed variables loaded on the same factor. We also found differences between the weight groups on the area of the anterior portion of the CC, but not the overall CC. Only the Controlled Oral Word Association Test (COWAT) was significantly correlated with the area of the anterior portion of the CC. In the obese group, 32.4% met criteria for MetS. No differences were found between obese participants with or without MetS and none of the MetS factors contributed consistently to cognitive performance. CONCLUSIONS: Obese adolescents show slower cognitive processing speed while maintaining equivalent performance on executive functioning compared with their healthy weight peers. The group differences in the anterior portion of the CC, responsible for frontal lobe interhemispheric communication, may in part explain our processing speed findings. Future studies should include a longitudinal design and diffusion tensor imaging to examine the integrity of white matter.

Outcomes of The BODY Project: A Program to Halt Obesity and Its Medical Consequences in High School Students.

Adolescent obesity continues to be a major public health issue with a third of American adolescents being overweight or obese. Excess weight is associated with cardiovascular risk factors and pre-diabetes. High school students identified as carrying excess weight [body mass index (BMI) ≥25 kg/m(2), or BMI percentile ≥85 %] were invited to participate in The BODY Project, an intervention that included a medical evaluation and a personalized medical report of the results of that evaluation sent to the parent/guardian at home. The medical evaluation and report was repeated 12 months later. The reports also contained advice on how the individual student could modify their lifestyle to improve the specific medical parameters showing abnormalities. Outcomes were change in BMI, blood pressure, high-density lipoprotein (HDL), low-density lipoprotein (LDL), fasting glucose, and fasting insulin. Students participating in The BODY Project intervention demonstrated modest, yet significant, reductions in BMI (p < 0.001) 1 year later, and also had significant improvements in systolic blood pressure (p < 0.001) and cholesterol profile (HDL p = 0.002; LDL p < 0.001) at follow-up. The BODY Project, by means of a minimal educational program anchored on the principle of teachable moments around the students' increased perception of their own risk for disease from the medical abnormalities uncovered, demonstrates evidence of potential effectiveness in addressing adolescent obesity.

Obesity, metabolic syndrome, and insulin resistance in urban high school students of minority race/ethnicity.

OBJECTIVES: To determine the point prevalences of metabolic syndrome (MetS) and its components among healthy weight, overweight, and obese inner-city public high school students, to compare the prevalences of MetS when using 2 different definitions (one with the impaired fasting glucose [IFG] level and the other with a homeostasis model assessment of insulin resistance [HOMA-IR] of 3.99 or higher to define the glucose regulation component), and to compare the degree to which HOMA-IR and fasting glucose level are associated with the other MetS components. DESIGN: Cross-sectional analysis. SETTING: Two New York City public high schools, from April 2008 through August 2011. PARTICIPANTS: Convenience sample of 1185 high school youth, comprising predominantly Hispanic and African American students from low-income households, participating in The Banishing Obesity and Diabetes in Youth Project, a medical screening and education program. MAIN OUTCOME MEASURES: Prevalences of the following individual MetS components: IFG threshold, HOMA-IR, hypertension, central adiposity, hypertriglyceridemia, and low high-density lipoprotein cholesterol. Rates of MetSIFG and MetSHOMA-IR were also assessed. RESULTS: MetSIFG and MetSHOMA-IR point prevalences were both 0.3% in the healthy weight group; they were 2.6% and 5.9%, respectively, in the overweight group and were 22.9% and 35.1%, respectively, in the obese group (P < .05 for both). An IFG threshold of 100 mg/dL or higher was found in 1.0% of participants, whereas a HOMA-IR of 3.99 or higher was found in 19.5% of participants. CONCLUSIONS: An elevated HOMA-IR is much more sensitive than an IFG threshold in identifying adolescents with metabolic dysregulation. Using a HOMA-IR threshold of 3.99 identifies more youth with MetS than using an IFG threshold of 100 mg/dL. In addition to increasing the sensitivity of MetS detection, HOMA-IR has a much higher association with the other MetS components than the IFG threshold and may better reflect a unified underlying pathologic process useful to identify youth at risk for disease.

Impact of metabolic syndrome on cognition and brain: a selected review of the literature.

Metabolic syndrome (MetS), a clustering of risk factors for type 2 diabetes mellitus and cardiovascular disease, has been associated with cognitive dysfunction and brain abnormalities. This review describes the literature on the impact of MetS on brain and cognition and suggests directions for future research. A literature search for reports of MetS and cognition and brain imaging was conducted for both nonelderly adults and adolescents. No studies were found describing MetS and brain or cognition among adolescents; therefore, we also included studies investigating individual components of MetS in this age group. Most studies found associations between MetS and cognitive dysfunction. Multiple cognitive domains were affected by MetS in adults. In adolescents, the majority of findings were in executive functioning. Brain imaging literature in adults implicated MetS in ischemic stroke, white matter alterations, and altered brain metabolism. For adolescents, individual MetS factors were linked to volume losses in the hippocampus and frontal lobes. MetS negatively impacts cognitive performance and brain structure. Potential explanatory models include impaired vascular reactivity, neuroinflammation, oxidative stress, and abnormal brain lipid metabolism. We posit that insulin resistance-associated impairment in cerebrovascular reactivity is an important mechanism underlying brain deficits seen in MetS.

The Banishing Obesity and Diabetes in Youth (BODY) Project: description and feasibility of a program to halt obesity-associated disease among urban high school students.

Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are rising dramatically in adolescents in parallel with excess weight. The Banishing Obesity and Diabetes in Youth (BODY) Project, is a school-based intervention that medically screens overweight and obese high school students, provides personalized feedback, and connects to appropriate healthcare. Body mass index (BMI) was determined for 1,526 students in one New York City public high school with a school-based health center (SBHC). Overweight and obese students (n = 640) were invited to complete a medical evaluation that included a survey, blood pressure and blood tests. 328/640 (51%) eligible students returned signed parental consent and participated. All participants received a personalized report detailing their results along with specific recommendations on how to improve their health. Parents of participants with results outside healthy ranges (82%; 270/328) were called and mailed referral letters to connect with healthcare services. Project staff reached by telephone 74% (199/270) of those families and 29% (58/199) stated that the report led them to make arrangements to see a healthcare provider. Most students (83%; 273/328) were registered at the SBHC, and we shared their medical results with them so they could follow-up with the students. The BODY Project is a feasible program for urban schools with a SBHC. This may allow effective prevention of T2DM, and CVD from dyslipidemia and hypertension.

Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions.

The rates of type 2 diabetes (T2DM) continue to parallel the rising rates of obesity in the United States, increasingly affecting adolescents as well as adults. Hippocampal and frontal lobe reductions have been found in older adults with type 2 diabetes, and we sought to ascertain if these brain alterations were also present in obese adolescents with T2DM. In a cross-sectional study we compared MRI-based regional brain volumes of 18 obese adolescents with T2DM and 18 obese controls without evidence of marked insulin resistance. Groups were matched on age, sex, school grade, ethnicity, socioeconomic status, body mass index, and waist circumference. Relative to obese controls, adolescents with T2DM had significantly reduced hippocampal and prefrontal volumes, and higher rates of global cerebral atrophy. Hemoglobin A1c, an index of long-term glycemic control, was inversely associated with prefrontal volume and positively associated with global cerebral atrophy (both p < 0.05). Brain integrity is negatively impacted by T2DM already during adolescence, long before the onset of overt macrovascular disease. Paralleling the findings of greater vascular and renal complications among obese adolescents with severe insulin resistance and T2DM relative to their age-matched peers with type 1 diabetes, we find clear evidence of possible brain complications. Our findings call for aggressive and early intervention to limit the negative impact of obesity-associated insulin resistance leading to T2DM on the developing brains of adolescents.

Disinhibited eating in obese adolescents is associated with orbitofrontal volume reductions and executive dysfunction.

In adults, obesity has been associated with disinhibited eating, decreased cortical gray matter (GM) volume, and lower performance on cognitive assessments. Much less is known about these relationships in adolescence and there are no studies assessing behavioral, cognitive, and neurostructural measures in the same group of study participants. This study examined the relationship between obesity, executive function, disinhibition, and brain volumes in relatively healthy youth. Participants included 54 obese and 37 lean adolescents. Participants received a cognitive battery, questionnaires of eating behaviors, and magnetic resonance imaging (MRI). Neuropsychological assessments included tasks targeting frontal lobe function. Eating behaviors were determined using the Three Factor Eating Questionnaire (TFEQ), and structural MRIs were performed on a 1.5 T Siemens Avanto MRI System (Siemens, Erlangen, Germany) to determine brain GM volumes. Lean and obese adolescents were matched on age, years of education, gender, and socioeconomic status. Relative to lean adolescents, obese participants had significantly higher ratings of disinhibition on the TFEQ, lower performance on the cognitive tests, and lower orbitofrontal cortex (OFC) volume. Disinhibition significantly correlated with BMI, Stroop color-word score, and OFC volume. This is the first report of these associations in adolescents and point to the importance of better understanding the associations between neurostructural deficits and obesity.

Metabolic syndrome is associated with learning and recall impairment in middle age.

AIMS: To determine whether middle-aged individuals with metabolic syndrome, both with and without type 2 diabetes, exhibit cognitive impairments, and to determine the role of each metabolic syndrome component in those associations. METHODS: 143 participants were drawn from ongoing studies of normal aging. Metabolic syndrome was diagnosed in 73 participants (age: 60.4 +/- 8.4 years), who were contrasted with 70 age- and education-matched controls. RESULTS: Metabolic syndrome was associated with reductions in recall (p = 0.006), lower overall intellectual functioning (p = 0.013), and nearly significant reductions in learning (p = 0.066) and executive functioning (p = 0.050). These effects were only marginally attenuated when controlling for type 2 diabetes diagnosis. Of the 5 components of the metabolic syndrome, insulin resistance was the only significant predictor of variance in learning and recall. In addition, the number of metabolic syndrome criteria met was inversely associated with cognitive performance. CONCLUSIONS: These results indicate that impairments in cognitive functioning associated with metabolic syndrome and type 2 diabetes may begin as early as middle age and are primarily due to insulin resistance. These results demonstrate the importance of screening at-risk adults for insulin resistance in order to initiate lifestyle modifications to reverse or prevent these cognitive changes.

Neuroimaging supports central pathology in familial dysautonomia.

Familial dysautonomia (FD) is a hereditary peripheral and central nervous system disorder with poorly defined central neuropathology. This prospective pilot study aimed to determine if MRI would provide objective parameters of central neuropathology. There were 14 study subjects, seven FD individuals (18.6 +/- 4.2 years, 3 female) and seven controls (19.1 +/- 5.8 years, 3 female). All subjects had standardized brain MRI evaluation including quantitative regional volume measurements, diffusion tensor imaging (DTI) for assessment of white matter (WM) microstructural integrity by calculation of fractional anisotropy (FA), and proton MR spectroscopy ((1)H MRS) to assess neuronal health. The FD patients had significantly decreased FA in optic radiation (p = 0.009) and middle cerebellar peduncle (p = 0.004). Voxel-wise analysis identified both GM and WM microstructural damage among FD subjects as there were nine clusters of WM FA reductions and 16 clusters of GM apparent diffusion coefficient (ADC) elevations. Their WM proportion was significantly decreased (p = 0.003) as was the WM proportion in the frontal region (p = 0.007). (1)H MRS showed no significant abnormalities. The findings of WM abnormalities and decreased optic radiation and middle cerebellar peduncle FA in the FD study group, suggest compromised myelination and WM micro-structural integrity in FD brains. These neuroimaging results are consistent with clinical visual abnormalities and gait disturbance. Furthermore the frontal lobe atrophy is consistent with previously reported neuropsychological deficits.

Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes.

Declarative memory impairment is frequently reported among adults with type 2 diabetes mellitus (T2DM), who also demonstrate hippocampal volume reduction. Our goals were to ascertain whether emotional memory, which is mediated by neural circuits overlapping those of declarative memory, is also affected. In addition we wanted to characterize cerebral white matter (WM) involvement in T2DM. We studied 24 middle-aged and elderly patients with T2DM who were free of obvious vascular pathology or a psychiatric disorder, and 17 age- and education-matched healthy individuals with no evidence of insulin resistance. We examined emotional and neutral memory and performed a whole-brain voxelwise WM assessment utilizing diffusion tensor imaging (DTI). We found clear evidence of impairment in declarative memory among diabetic subjects and in addition found some preliminary support to suggest a possible blunting of the memory facilitation by emotional material among female but not male diabetics. This report is also the first DTI assessment among individuals with T2DM, which after accounting for overt WM damage, revealed diffuse but predominantly frontal and temporal WM microstructural abnormalities, with extensive involvement of the temporal stem. Hierarchical regression analyses demonstrated that immediate, but not delayed, emotional memory performance was explained by temporal stem FA, independent of age, poor metabolic regulation, and systolic blood pressure. Given that the temporal lobe memory networks appear to be particularly vulnerable to the deleterious effects of T2DM, this may help explain the observed memory impairments among diabetics. Future efforts should better clarify, with a larger sample, whether emotional memory is affected in adults with T2DM and whether there are clear gender effects.

Plasma BDNF is reduced among middle-aged and elderly women with impaired insulin function: evidence of a compensatory mechanism.

Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to type 2 diabetes mellitus (T2DM), were matched with 41 healthy controls on gender, age, education, and IQ. Participants received complete medical, neurological, psychiatric, and neuropsychological evaluations. IIF individuals had significantly lower plasma BDNF levels than controls, particularly females, and higher BDNF levels were associated with poorer explicit memory in IIF females, suggesting that higher levels within this group may reflect the body's efforts to respond to damage. After accounting for age, education, and HbA1c, BDNF significantly predicted 13.1-23.5% of the variance in explicit memory in IIF women. These findings suggest that BDNF elevations within diseased groups may not always be a marker of health.

Modifiers of cognitive function and brain structure in middle-aged and elderly individuals with type 2 diabetes mellitus.

Cognitive deficits and hippocampal atrophy, features that are shared with aging and dementia, have been described in type 2 diabetes mellitus (T2DM). T2DM is associated with obesity, hypertension, dyslipidemia, hypothalamic pituitary adrenocortical (HPA) axis abnormalities and inflammation, all of which have been shown to negatively impact the brain. However, since most reports in T2DM focused on glycemic control, the relative contribution of these modifying factors to the impairments observed in T2DM remains unclear. We contrasted 41 middle-aged dementia-free volunteers with T2DM (on average 7 years since diagnosis) with 47 age-, education-, and gender-matched non-insulin resistant controls on cognition and brain volumes. HPA axis activity and other modifiers that accompany T2DM were assessed to determine their impact on brain and cognition. Individuals with T2DM had specific verbal declarative memory deficits, reduced hippocampal and prefrontal volumes, and impaired HPA axis feedback control. Diminished cortisol suppression after dexamethasone and dyslipidemia were associated with decreased cognitive performance, whereas obesity was negatively related to hippocampal volume. Moreover, prefrontal volume was influenced by worse glycemic control. Thus, obesity and altered cortisol levels may contribute to the impact of T2DM on the hippocampal formation, resulting in decreased verbal declarative memory performance.

Retinal vessel abnormalities are associated with elevated fasting insulin levels and cerebral atrophy in nondiabetic individuals.

OBJECTIVE: To determine the impact of insulin resistance short of diabetes on the arteriolar-to-venular ratio (AVR) and whether AVR is related to cerebral atrophy. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-six nondiabetic subjects with normal glucose tolerance and varying degrees of insulin resistance ranging in age from 43 to 77 years. METHODS: Insulin resistance was assessed by fasting insulin and the homeostasis model assessment. Arteriolar-to-venular ratio was determined using digital retinal photography with a nonmydriatic camera, and retinal data were analyzed using a reliable semiautomated method. Cerebral atrophy was derived by means of manual tracing and thresholding procedures on structural magnetic resonance images. MAIN OUTCOME MEASURES: Arteriolar-to-venular ratio and cerebral atrophy. RESULTS: Hyperinsulinemia negatively impacted AVR. Furthermore, AVR was associated with cerebral atrophy. Both of these findings were independent of the effects of age and hypertension. CONCLUSIONS: These novel findings indicate that insulin resistance short of diabetes and independent of age and hypertension has a negative impact on retinal vessel health. Moreover, impaired retinal vessel health related to brain atrophy also was independent of hypertension and white matter hyperintensities. Given the connections between retinal and cerebral vasculature, this may offer a partial explanation for the presence of cognitive and brain abnormalities among individuals with insulin resistance. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.