Obesity, fitness, and brain integrity in adolescence.

OBJECTIVE: We set out to ascertain the relationship between insulin resistance, fitness, and brain structure and function in adolescents. DESIGN AND METHODS: We studied 79 obese and 51 non-obese participants who were recruited from the community, all without type 2 diabetes mellitus. All participants received medical, endocrine, neuropsychological, and MRI evaluations as well as a 6-minute walk test that was used to estimate fitness (maximal oxygen consumption). RESULTS: Obese adolescents had significantly thinner orbitofrontal cortices and performed significantly worse on Visual Working Memory tasks and the Digit Vigilance task. Insulin sensitivity and maximal oxygen consumption (VO2 max) were both highly correlated with central obesity and orbitofrontal cortical thickness, although insulin sensitivity was the stronger predictor for orbitofrontal cortical thickness. We also found that VO2 max was the only significant physiological variable related to visual working memory. CONCLUSIONS: This is the first study to report positive associations between insulin resistance, VO2 max, and frontal lobe brain integrity in adolescents. Given the importance of brain health for learning and school performance, we conclude that schools should also emphasize physical fitness in order to maintain structural and functional brain integrity and facilitate academic achievement.

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.

Three-dimensional mapping of the creatine kinase enzyme reaction rate in muscles of the lower leg.

Phosphorus ((31) P) magnetization transfer (MT) techniques enable the non-invasive measurement of metabolic turnover rates of important enzyme-catalyzed reactions, such as the creatine kinase reaction (CK), a major transducing reaction involving adenosine triphosphate and phosphocreatine. Alteration in the kinetics of the CK reaction rate appears to play a central role in many disease states. In this study, we developed and implemented at ultra-high field (7T) a novel three-dimensional (31) P-MT imaging sequence that maps the kinetics of CK in the entire volume of the lower leg at relatively high resolution (0.52 mL voxel size), and within acquisition times that can be tolerated by patients (below 60 min). We tested the sequence on five healthy and two clinically diagnosed type 2 diabetic subjects. Overall, we obtained measurements that are in close agreement with measurements reported previously using spectroscopic methods. Importantly, our spatially resolved method allowed us to measure local CK reaction rate constants and metabolic fluxes in individual muscles in a non-invasive manner. Furthermore, it allowed us to detect variations of the CK rates of different muscles, which would not have been possible using unlocalized MRS methods. The results of this work suggest that 3D mapping of the CK reaction rates and metabolic fluxes can be achieved in the skeletal muscle in vivo at relatively high spatial resolution and with acquisition times well tolerated by patients. The ability to measure bioenergetics simultaneously in large areas of muscles will bring new insights into possible heterogeneous patterns of muscle metabolism associated with several diseases and serve as a valuable tool for monitoring the efficacy of interventions.

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.

Paediatric obesity and metabolic syndrome associations with cognition and the brain in youth: Current evidence and future directions.

Obesity and components of the metabolic syndrome (MetS) are associated with differences in brain structure and function and in general and food-related cognition in adults. Here, we review evidence for similar phenomena in children and adolescents, with a focus on the implications of extant research for possible underlying mechanisms and potential interventions for obesity and MetS in youth. Current evidence is limited by a relative reliance on small cross-sectional studies. However, we find that youth with obesity and MetS or MetS components show differences in brain structure, including alterations in grey matter volume and cortical thickness across brain regions subserving reward, cognitive control and other functions, as well as in white matter integrity and volume. Children with obesity and MetS components also show some evidence for hyperresponsivity of food reward regions and hyporesponsivity of cognitive control circuits during food-related tasks, altered brain responses to food tastes, and altered resting-state connectivity including between cognitive control and reward processing networks. Potential mechanisms for these findings include neuroinflammation, impaired vascular reactivity, and effects of diet and obesity on myelination and dopamine function. Future observational research using longitudinal measures, improved sampling strategies and study designs, and rigorous statistical methods, promises to further illuminate dynamic relationships and causal mechanisms. Intervention studies targeted at modifiable biological and behavioural factors associated with paediatric obesity and MetS can further inform mechanisms, as well as test whether brain and behaviour can be altered for beneficial outcomes.

Type 2 diabetes affects hippocampus volume differentially in men and women.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been shown to result in medical complications on several organ systems including the kidneys, eyes, cardiovascular system, and most recently described the brain, including the hippocampus. There is also evidence that females are disproportionately affected by these medical complications. Brain volume reductions have also been associated with chronic low-grade inflammation and dyslipidaemia. This study investigated the relationships among T2DM, gender, inflammation, dyslipidaemia, and hippocampal volumes. METHOD: Participant groups consisted of 40 obese adults with T2DM and 47 lean adults, group-matched on age, gender, race, and education. Each participant underwent medical examination including a standard panel of blood tests, a magnetic resonance imaging, and cognitive evaluation. RESULTS: We show that there is a gender difference in the association of T2DM and hippocampal volumes: diabetic women are most affected despite having better glucose control than their male counterparts. Although females with T2DM had disproportionately lower high density lipoprotein as well as better haemoglobin A1c, neither of these results explained why females with T2DM had the smallest hippocampal volumes. CONCLUSIONS: These important findings indicate that in addition to the higher rate of traditional medical complication, females with T2DM are likely to suffer more brain complications than males. These observations, if supported by larger studies, suggest that in the future gender could be considered when customizing diabetes treatment.

Effectiveness of a cognitive behavioral weight management intervention in obese patients with psychotic disorders compared to patients with nonpsychotic disorders or no psychiatric disorders: results from a 12-month, real-world study.

OBJECTIVE: Studies of behavioral weight loss intervention in patients with psychotic disorders are sparse, and its efficacy compared to other obese patients is unknown. Therefore, we compared the effect of a cognitive-behavioral weight loss intervention in obese subjects with psychotic disorders, other psychiatric diagnoses, and without psychiatric disorders. METHODS: A 12-month naturalistic study of weekly group or individual cognitive-behavioral weight management in 222 consecutively enrolled obese patients (body mass index [BMI], 43.7 ± 9.6 kg/m2) with psychotic spectrum disorders (PSDs, n = 47), other psychiatric disorders (OPDs, n = 49), and no psychiatric disorder (NPD, n = 126). RESULTS: Patients with PSD had greater treatment persistence (48.9%) and longer treatment duration (8.7 ± 4.4 months) than those with OPD (22.4% and 5.4 ± 4.3 months) and NPD (22.2% and 4.9 ± 4.7 months) (P < 0.01 for all; number needed to treat, 3). In last-observation-carried-forward analyses, patients with PSD had greater percent baseline weight loss at 12 months (5.1% ± 9.3%) than patients with OPD and with NPD (2.7% ± 5.5% and 2.4% ± 6.3%); greater percent BMI loss at 9 and 12 months than both groups (P < 0.05 for all) and greater BMI loss at 9 months (2.1 ± 3.5 kg/m2) and 12 months (2.3 ± 4.1 kg/m2) than NPD patients (1.1 ± 2.3 and 1.2 ± 2.4 kg/m2). Furthermore, weight loss of 5% or more occurred in 42.6% of patients with PSD versus 18.4% and 23.0% in OPD and NPD patients (P < 0.01 for all; numbers needed to treat, 5 and 6). The strongest weight loss predictor was treatment duration (ß = 0.51-0.54; P < 0.001). Attrition was predicted by NPD (P = 0.001) and OPD group status (P = 0.036), lower proportion of group sessions (P = 0.002), higher depression (P = 0.028), and lower baseline BMI (P = 0.030). CONCLUSIONS: Patients with PSD had greater weight loss than other obese patients. Nonadherence and depression should be targeted to enhance weight loss success.

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.

Does obesity-associated insulin resistance affect brain structure and function of adolescents differentially by sex?

Metabolic abnormalities affect the adolescent brain. For equivalent abnormalities in metabolism young people exhibit deficits in more cognitive domains than adults. We examine sex differences performance for adolescents with obesity/insulin resistance (IR) and evaluated how sex and IR effected frontal lobe structures and executive functioning. 125 adolescents underwent medical, cognitive, and brain-imaging assessments. Participants were categorized as insulin sensitive (IS) (QUICKI ≥ 0.350) or IR (QUICKI < 0.350). Degree of IR may affect brain and cognition differentially by sex. Females had positive associations between QUICKI and anterior cingulate cortex (ACC) volume, medial orbito-frontal cortex (OFC) thickness, and scores on the Stroop and Digit Symbol Substitution (DSST) tests. Females with IR tended to have thinner insular cortices. No such associations were found in males. In female adolescents, IR may negatively affect brain structure and function. No such effects were found for males. Although needing more development, hormonal effects and inflammation are potential contributors.

Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease.

Background: Neurometabolic abnormalities and amyloid-beta plaque deposition are important early pathophysiologic changes in Alzheimer's disease (AD). This study investigated the relationship between high-energy phosphorus-containing metabolites, glucose uptake, and amyloid plaque using phosphorus magnetic resonance spectroscopy (31P-MRS) and positron emission tomography (PET). Methods: We measured 31P-MRS, fluorodeoxyglucose (FDG)-PET, and Pittsburgh Compound B (PiB)-PET in a cohort of 20 cognitively normal middle-aged adults at risk for AD. We assessed 31P-MRS reliability by scanning a separate cohort of 13 healthy volunteers twice each. We calculated the coefficient-of-variation (CV) of metabolite ratios phosphocreatine-to-adenosine triphosphate (PCr/α-ATP), inorganic phosphate (Pi)-to-α-ATP, and phosphomonoesters-to-phosphodiesters (PME/PDE), and pH in pre-defined brain regions. We performed linear regression analysis to determine the relationship between 31P measurements and tracer uptake, and Dunn's multiple comparison tests to investigate regional differences in phosphorus metabolism. Finally, we performed linear regression analysis on 31P-MRS measurements in both cohorts to investigate the relationship of phosphorus metabolism with age. Results: Most regional 31P metabolite ratio and pH inter- and intra-day CVs were well below 10%. There was an inverse relationship between FDG-SUV levels and metabolite ratios PCr/α-ATP, Pi/α-ATP, and PME/PDE in several brain regions in the AD risk group. There were also several regional differences among 31P metabolites and pH in the AD risk group including elevated PCr/α-ATP, depressed PME/PDE, and elevated pH in the temporal cortices. Increased PCr/α-ATP throughout the brain was associated with aging. Conclusions: Phosphorus spectroscopy in the brain can be performed with high repeatability. Phosphorus metabolism varies with region and age, and is related to glucose uptake in adults at risk for AD. Phosphorus spectroscopy may be a valuable approach to study early changes in brain energetics in high-risk populations.

Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study.

Background Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. Methods and Results We examined associations of baseline platelet function with incident dementia risk in the community-based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause-specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow-up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper-responders, as well as the platelet response to 0.1 µmol/L epinephrine. Conclusions Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20-year follow-up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.

Lower extremity MRI following 10-week supervised exercise intervention in patients with diabetic peripheral neuropathy.

INTRODUCTION: The purpose of this study was to characterize using MRI the effects of a 10-week supervised exercise program on lower extremity skeletal muscle composition, nerve microarchitecture, and metabolic function in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: Twenty participants with DPN completed a longitudinal trial consisting of a 30-day control period, during which subjects made no change to their lifestyle, followed by a 10-week intervention program that included three supervised aerobic and resistance exercise sessions per week targeting the upper and lower extremities. The participants' midcalves were scanned with multinuclear MRI two times prior to intervention (baseline1 and baseline2) and once following intervention to measure relaxation times (T1, T1ρ, and T2), phosphocreatine recovery, fat fraction, and diffusion parameters. RESULTS: There were no changes between baseline1 and baseline2 MRI metrics (p>0.2). Significant changes (p<0.05) between baseline2 and postintervention MRI metrics were: gastrocnemius medialis (GM) T1 -2.3%±3.0% and soleus T2 -3.2%±3.1%. Trends toward significant changes (0.050.3) and tibial nerve fractional anisotropy (p>0.6) and apparent diffusion coefficient (p>0.4). CONCLUSIONS: The 10-week supervised exercise intervention program successfully reduced adiposity and altered resting tissue properties in the lower leg in DPN. Gastrocnemius mitochondrial oxidative capacity and tibial nerve microarchitecture changes were not observed, either due to lack of response to therapy or to lack of measurement sensitivity.

The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study.

Objective: Active neutrophils are important contributors to Alzheimer's disease (AD) pathology through the formation of capillary stalls that compromise cerebral blood flow (CBF) and through aberrant neutrophil signaling that advances disease progression. The neutrophil to lymphocyte ratio (NLR) is a proxy of neutrophil-mediated inflammation, and higher NLR is found in persons diagnosed with clinical AD. The objective of this study was to investigate whether increased NLR in older adults is independently associated with the risk of subsequent dementia. Methods: We examined associations of baseline NLR with incident dementia risk in the community-based Framingham Heart Study (FHS) longitudinal cohorts. The association between NLR and risk of dementia was evaluated using the cumulative incidence function (CIF) and inverse probability-weighted Cox proportional cause-specific hazards regression models, with adjustment for age, sex, body mass index (BMI), systolic and diastolic blood pressure, diabetes, current smoking status, low-density lipoprotein (LDH), high-density lipoprotein (LDL), total cholesterol, triglycerides, and history of cardiovascular disease (CVD). Random forest survival models were used to evaluate the relative predictive value of the model covariates on dementia risk. Results: The final study sample included 1,648 participants with FHS (average age, 69 years; 56% women). During follow-up (median, 5.9 years), we observed 51 cases of incident dementia, of which 41 were AD cases. Results from weighted models suggested that the NLR was independently associated with incident dementia, and it was preceded in predictive value only by age, history of CVD, and blood pressure at baseline. Conclusion: Our study shows that individuals with higher NLR are at a greater risk of subsequent dementia during a 5.9-year follow-up period. Further evaluating the role of neutrophil-mediated inflammation in AD progression may be warranted.

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.

The application of the first order system transfer function for fitting the California Verbal Learning Test learning curve.

Very few attempts have been made to apply a mathematical model to the learning curve in the California Verbal Learning Test list A immediate recall. Our rationale was to find out whether modeling of the learning curve can add additional information to the standard CVLT [corrected] measures. We applied a standard transfer function in the form Y = B3*exp(-B2*(X-1))+B4*(1-exp(-B2*(X-1))), where X is the trial number; Y is the number of recalled correct words, B2 is the learning rate, B3 is readiness to learn and B4 is ability to learn. The coefficients of the model were found to be independent measures not duplicating standard CVLT [corrected] measures. Regression analysis revealed that readiness to learn (B3) and ability to learn (B4) were significantly (p < .05) higher in a group of healthy participants than in a group of participants with type 2 diabetes mellitus (T2DM), but the learning rate (B2) did not differ (p > .2). The proposed model is appropriate for clinical application and as a guide for research and may be used as a good supplemental tool for the CVLT [corrected] and similar memory tests.

Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly.

AIMS/HYPOTHESIS: Midlife obesity is a risk factor for dementia. We investigated the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) core Alzheimer's disease (AD) biomarkers in healthy elderly. METHODS: We selected controls from ADNI2 with CSF AD biomarkers and/or fluorodeoxyglucose positron emission tomography (FDG-PET) and 3T-MRI. We measured cortical thickness, FDG uptake, and CSF amyloid beta (Aß)1-42, p-tau, and t-tau levels. We performed regression analyses between these biomarkers and body mass index (BMI). RESULTS: We included 201 individuals (mean age 73.5 years, mean BMI 27.4 kg/m2). Higher BMI was related to less cortical thickness and higher metabolism in brain areas typically not involved in AD (family-wise error [FWE] <0.05), but not to AD CSF biomarkers. It is notable that the impact of obesity on brain metabolism and structure was also found in amyloid negative individuals. CONCLUSIONS/INTERPRETATION: In the cognitively unimpaired elderly, obesity has differential effects on brain metabolism and structure independent of an underlying AD pathophysiology.

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.

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.

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.

Dissociation of cognitive and emotional empathy in adults with Asperger syndrome using the Multifaceted Empathy Test (MET).

Empathy is a multidimensional construct consisting of cognitive (inferring mental states) and emotional (empathic concern) components. Despite a paucity of research, individuals on the autism spectrum are generally believed to lack empathy. In the current study we used a new, photo-based measure, the Multifaceted Empathy Test (MET), to assess empathy multidimensionally in a group of 17 individuals with Asperger syndrome (AS) and 18 well-matched controls. Results suggested that while individuals with AS are impaired in cognitive empathy, they do not differ from controls in emotional empathy. Level of general emotional arousability and socially desirable answer tendencies did not differ between groups. Internal consistency of the MET's scales ranged from .71 to .92, and convergent and divergent validity were highly satisfactory.