Victoria Sweat

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.

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.

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.

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.

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.

Cognitive impairment in nondiabetic middle-aged and older adults is associated with insulin resistance

To determine whether the cognitive impairments observed in adults with type 2 diabetes mellitus (T2DM) exist in preclinical disease, we compared 38 adult participants with evidence of insulin resistance (IR) to 54 age-, gender-, and education-matched control participants on a battery of neuropsychological tests. We found that participants with IR had performance reductions in declarative memory and executive functioning. When we examined IR simultaneously with other biomedical indicators with which it co-occurs, only IR itself was associated with declarative memory, and hemoglobin A1c (HbA1c) was associated with executive functioning and working memory. We conclude that individuals with insulin resistance already demonstrate similar reductions in cognitive performance as those described in T2DM.

Subjective memory complaints in aging are associated with elevated cortisol levels

The origin and clinical significance of subjective memory complaints among middle aged and older individuals is not well understood. Associations with objective memory impairments, personality traits or mood disturbances have been reported. Elevated cortisol levels occur in aging and depression and causal links to cognitive or emotional problems have been suggested. The goal of this study was to investigate the associations between basal and feedback indices of cortisol regulation and subjective memory impairment in a sample of healthy middle aged and older subjects (mean age 61.8 years) with (n=27) and without (n=19) subjective memory complaints. Participants with memory complaints had both higher basal cortisol levels and higher cortisol levels after dexamethasone. There was a significant group by gender interaction for basal cortisol levels, where women without memory complaints showed significantly lower cortisol levels, whereas no such difference was found for the men. All effects were not due to slight differences in depression scores. Differences in personality traits or in stress susceptibility might underlie the present findings. Future studies of memory complaints should take a comprehensive approach including relevant endocrine parameters.

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.

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 bodys 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.

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.