Objective
To ascertain whether pediatric obesity without clinically significant insulin resistance (IR) impacts brain structure and function.
Methods
Thirty obese and 30 matched lean adolescents, all ...without clinically significant IR or a diagnosis of metabolic syndrome (MetS), received comprehensive endocrine, neuropsychological, and MRI evaluations.
Results
Relative to lean adolescents, obese non‐IR adolescents had significantly lower academic achievement (i.e., arithmetic and spelling) and tended to score lower on working memory, attention, psychomotor efficiency, and mental flexibility. In line with our prior work on adolescent MetS, memory was unaffected in uncomplicated obesity. Reductions in the thickness of the orbitofrontal and anterior cingulate cortices as well as reductions of microstructural integrity in major white matter tracts without gross volume changes were also uncovered.
Conclusions
It was documented, for the first time, that adolescents with uncomplicated obesity already have subtle brain alterations and lower performance in selective cognitive domains. When interpreting these preliminary data in the context of our prior reports of similar, but more extensive brain findings in obese adolescents with MetS and T2DM, it was concluded that “uncomplicated” obesity may also result in subtle brain alterations, suggesting a possible dose effect with more severe metabolic dysregulation giving rise to greater abnormalities.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The prevalence of metabolic syndrome (MetS) parallels the rise in childhood obesity. MetS is associated with neurocognitive impairments in adults, but this is thought to be a long-term effect of poor ...metabolism. It would be important to ascertain whether these brain complications are also present among adolescents with MetS, a group without clinically manifest vascular disease and relatively short duration of poor metabolism.
Forty-nine adolescents with and 62 without MetS, matched on age, socioeconomic status, school grade, gender, and ethnicity, received endocrine, MRI, and neuropsychological evaluations.
Adolescents with MetS showed significantly lower arithmetic, spelling, attention, and mental flexibility and a trend for lower overall intelligence. They also had, in a MetS-dose-related fashion, smaller hippocampal volumes, increased brain cerebrospinal fluid, and reductions of microstructural integrity in major white matter tracts.
We document lower cognitive performance and reductions in brain structural integrity among adolescents with MetS, thus suggesting that even relatively short-term impairments in metabolism, in the absence of clinically manifest vascular disease, may give rise to brain complications. In view of these alarming results, it is plausible that obesity-associated metabolic disease, short of type 2 diabetes mellitus, may be mechanistically linked to lower the academic and professional potential of adolescents. Although obesity may not be enough to stir clinicians or even parents into action, these results in adolescents strongly argue for an early and comprehensive intervention. We propose that brain function be introduced among the parameters that need to be evaluated when considering early treatment of childhood obesity.
Who Cares? Revisiting Empathy in Asperger Syndrome Rogers, Kimberley; Dziobek, Isabel; Hassenstab, Jason ...
Journal of autism and developmental disorders,
04/2007, Volume:
37, Issue:
4
Journal Article
Peer reviewed
A deficit in empathy has consistently been cited as a central characteristic of Asperger syndrome (AS), but previous research on adults has predominantly focused on cognitive empathy, effectively ...ignoring the role of affective empathy. We administered the Interpersonal Reactivity Index (IRI), a multi-dimensional measure of empathy, and the Strange Stories test to 21 adults with AS and 21 matched controls. Our data show that while the AS group scored lower on the measures of cognitive empathy and theory of mind, they were no different from controls on one affective empathy scale of the IRI (empathic concern), and scored higher than controls on the other (personal distress). Therefore, we propose that the issue of empathy in AS should be revisited.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Abstract The consolidation of spatial navigational memory during sleep is supported by electrophysiological and behavioral evidence. The features of sleep that mediate this ability may change with ...aging, as percentage of slow wave sleep is canonically thought to decrease with age, and slow waves are thought to help orchestrate hippocampal-neocortical dialogue that supports systems level consolidation. In this study, groups of younger and older subjects performed timed trials before and after polysomnographically recorded sleep on a 3D spatial maze navigational task. Although younger subjects performed better than older subjects at baseline, both groups showed similar improvement across pre-sleep trials. However, younger subjects experienced significant improvement in maze performance during sleep that was not observed in older subjects, without differences in morning psychomotor vigilance between groups. Older subjects had sleep quality marked by decreased amount of slow wave sleep and increased fragmentation of slow wave sleep, resulting in decreased slow wave activity. Across all subjects, frontal slow wave activity was positively correlated with both overnight change in maze performance and medial prefrontal cortical volume, illuminating a potential neuroanatomical substrate for slow wave activity changes with aging and underscoring the importance of slow wave activity in sleep-dependent spatial navigational memory consolidation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Dopamine mediates the rewarding effects of food that can lead to overeating and obesity, which then trigger metabolic neuroadaptations that further perpetuate excessive food consumption. We tested ...the hypothesis that the dopamine response to calorie intake (independent of palatability) in striatal brain regions is attenuated with increases in weight.
We used positron emission tomography with 11Craclopride to measure dopamine changes triggered by calorie intake by contrasting the effects of an artificial sweetener (sucralose) devoid of calories to that of glucose to assess their association with body mass index (BMI) in nineteen healthy participants (BMI range 21-35).
Neither the measured blood glucose concentrations prior to the sucralose and the glucose challenge days, nor the glucose concentrations following the glucose challenge vary as a function of BMI. In contrast the dopamine changes in ventral striatum (assessed as changes in non-displaceable binding potential of 11Craclopride) triggered by calorie intake (contrast glucose - sucralose) were significantly correlated with BMI (r = 0.68) indicating opposite responses in lean than in obese individuals. Specifically whereas in normal weight individuals (BMI <25) consumption of calories was associated with increases in dopamine in the ventral striatum in obese individuals it was associated with decreases in dopamine.
These findings show reduced dopamine release in ventral striatum with calorie consumption in obese subjects, which might contribute to their excessive food intake to compensate for the deficit between the expected and the actual response to food consumption.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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.
Context: There is evidence of both hypothalamic-pituitary-adrenocortical (HPA) axis and cognitive dysfunction in type 2 diabetes mellitus (T2DM). However, the exact nature and the associations ...between these abnormalities remain unclear.
Objectives: The aim of the study was to characterize the nature of the HPA dysregulation in T2DM and ascertain whether impaired cognition in T2DM could be attributed to these abnormalities.
Design: A cross-sectional study was performed, contrasting matched groups on HPA axis function and cognition by using the combined dexamethasone (DEX)/CRH test and a neuropsychological battery assessing declarative and working memory, attention, and executive function.
Setting: The study was conducted in a research clinic in an academic medical center.
Participants: Participants were volunteers functioning in the cognitively normal range. We studied 30 middle-aged individuals with T2DM, on average 7.5 yr since diabetes diagnosis, and 30 age-, gender-, and education-matched controls.
Main Outcome Measures: Basal cortisol levels, cortisol levels during the DEX/CRH test, and performance on neuropsychological tests were measured.
Results: Individuals with T2DM had elevated basal plasma cortisol levels, higher levels after DEX suppression, and a larger response to CRH (all P ≤ 0.005). Among individuals with T2DM, cortisol levels during the DEX/CRH test were positively associated with glycosylated hemoglobin (P = 0.05), independent of age, body mass index, hypertension, and dyslipidemia. Diabetic subjects showed cognitive impairments restricted to declarative memory. Across all subjects, declarative memory was inversely associated with cortisol levels; however, these associations were subsumed by glycemic control (glycosylated hemoglobin).
Conclusions: HPA hyperactivity and declarative memory deficits are present in T2DM. Both alterations may reflect the negative impact of poor glycemic control on the hippocampal formation.
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.
Poor glucose tolerance and memory deficits, short of dementia, often accompanies aging. The purpose of this study was to ascertain whether, among nondiabetic, nondemented middle-aged and elderly ...individuals, poorer glucose tolerance is associated with reductions in memory performance and smaller hippocampal volumes. We studied 30 subjects who were evaluated consecutively in an outpatient research setting. The composition of the participant group was 57% female and 68.6 ± 7.5 years of age; the participants had an average education of 16.2 ± 2.3 years, a score on the Mini Mental State Examination of 28.6 ± 1.5, a glycosylated hemoglobin (HbA1C) of 5.88 ± 0.74%, and a body mass index of 24.9 ± 4.1 kg/m2. Glucose tolerance was measured by an i.v. glucose tolerance test. Memory was tested by using the Wechsler Paragraphs recall tests at the time of administering the i.v. glucose tolerance test. The hippocampus and other brain volumes were measured by using validated methods on standardized MRIs. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. These associations were independent of age and Mini Mental State Examination scores. Therefore, these data suggest that metabolic substrate delivery may influence hippocampal structure and function. This observation may bring to light a mechanism for aging brain injury that may have substantial medical impact, given the large number of elderly individuals with impaired glucose metabolism.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
To determine if medial temporal lobe (MTL) atrophy rate, assessed by using an automated procedure over the initial time interval of a 6-year, three-time-point longitudinal study, is predictive of ...future memory decline.
Healthy elderly subjects (age, >60 years) were administered a comprehensive battery of neuropsychometric tests and underwent magnetic resonance (MR) imaging at baseline and two or more follow-up examinations. The rate of brain atrophy between the baseline and first follow-up examinations was assessed by using an automated procedure that included spatial coregistration of the two images and regional brain boundary shift analysis. At final observation, the 45 subjects were separated into a group of those who did and a group of those who did not show objective evidence of cognitive decline. A forward stepwise logistic regression model was used to identify variables that predicted decline.
Thirty-two subjects remained healthy, and 13 showed cognitive decline. Among subjects who showed cognitive decline, six declined after the second observation. MTL atrophy rate, through its interactions with sex and age, was the most significant predictor of decline. The overall accuracy of prediction was 89% (in 40 of 45 subjects), with 91% specificity (in 29 of 32 subjects) and 85% sensitivity (in 11 of 13 subjects).
Among healthy elderly individuals, increased MTL atrophy rate appears to be predictive of future memory decline.
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