Brain structure and obesity

Obesity is associated with increased risk for cardiovascular health problems including diabetes, hypertension, and stroke. These cardiovascular afflictions increase risk for cognitive decline and dementia, but it is unknown whether these factors, specifically obesity and Type II diabetes, are associated with specific patterns of brain atrophy. We used tensor‐based morphometry (TBM) to examine gray matter (GM) and white matter (WM) volume differences in 94 elderly subjects who remained cognitively normal for at least 5 years after their scan. Bivariate analyses with corrections for multiple comparisons strongly linked body mass index (BMI), fasting plasma insulin (FPI) levels, and Type II Diabetes Mellitus (DM2) with atrophy in frontal, temporal, and subcortical brain regions. A multiple regression model, also correcting for multiple comparisons, revealed that BMI was still negatively correlated with brain atrophy (FDR <5%), while DM2 and FPI were no longer associated with any volume differences. In an Analysis of Covariance (ANCOVA) model controlling for age, gender, and race, obese subjects with a high BMI (BMI > 30) showed atrophy in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus compared with individuals with a normal BMI (18.5–25). Overweight subjects (BMI: 25–30) had atrophy in the basal ganglia and corona radiata of the WM. Overall brain volume did not differ between overweight and obese persons. Higher BMI was associated with lower brain volumes in overweight and obese elderly subjects. Obesity is therefore associated with detectable brain volume deficits in cognitively normal elderly subjects. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Bariatric Surgery Induces White and Grey Matter Density Recovery in the Morbidly Obese: A Voxel‐Based Morphometric Study

Obesity is associated with lowered brain's grey (GM) and white matter (WM) density as measured by voxel‐based morphometry (VBM). Nevertheless, it remains unknown whether obesity has a causal influence on cerebral atrophy. We recruited 47 morbidly obese subjects (mean BMI = 42.2, SD = 4.0, 42 females and five males) eligible for bariatric surgery and 29 non‐obese subjects (mean BMI = 23.2, SD = 2.8, 23 females and six males) served as controls. Baseline scans were acquired with T1‐weighted magnetic resonance imaging (MRI) at 1.5 Tesla; obese participants were scanned again six months after the surgery. Local GM and WM densities were quantified using VBM. Full‐volume analyses were used for comparing baseline between‐group differences as well as the effects of surgery‐induced weight loss in the morbidly obese. Metabolic variables were used in linear models to predict WM and GM densities. Obese subjects had initially lower GM densities in widespread cortical areas including frontal, parietal, and temporal regions as well as insulae. Lower WM densities were observed throughout the WM. Bariatric surgery and concomitant weight loss resulted in global increase in WM density. Grey matter increase was limited to occipital and inferior temporal regions. Metabolic variables were associated with brain densities. We conclude that weight loss results in global recovery of WM as well as local recovery of grey matter densities. These changes likely reflect improved brain tissue integrity. Hum Brain Mapp 37:3745–3756, 2016. © 2016 Wiley Periodicals, Inc.     

Association of obesity with cerebral microbleeds in neurologically asymptomatic elderly subjects

Obesity is associated with an increased risk of cardiovascular disease, but few studies have investigated the effects of obesity on subclinical cerebrovascular disease. Cerebral microbleeds (CMBs) are radiological markers of cerebral small vessel disease and reflect underlying vasculopathy. In this context, we assessed whether obesity was related to CMBs and to CMB subtypes categorized by location. Neurologically asymptomatic elderly subjects (n?=?1,251; age????65?years) who visited for routine health check-ups were included in this study. Cerebral microbleeds were evaluated through T2*-weighted gradient-recalled echo MRI. The subjects were categorized into two groups depending on CMB location: strictly lobar and deep or infratentorial microbleeds. Body mass index was calculated, and obesity was defined using the World Health Organization Western Pacific Regional Office criteria. A total of 120 (9.6?%) subjects were found to have CMBs. As the severity of obesity increased, the prevalence of CMBs increased. Compared with the normal weight group and after controlling possible confounders, the risk of deep or infratentorial microbleeds was significantly increased in the overweight group [odds ratio (OR) 2.32, 95?% confidence interval (CI) 1.19?C4.53], and the obese group (OR 2.17, 95?% CI 1.14?C4.13). However, the ORs for the strictly lobar microbleeds were not increased in either the overweight or obese groups. Obesity was associated with deep or infratentorial microbleeds. This finding suggests that obesity affects cerebral small vessels through arteriosclerotic vasculopathy. Based on our findings, we postulate that obesity is associated with the presence of subclinical and bleeding-prone cerebrovascular disease in the elderly.     

老年轻度认知功能损害的脑磁共振显像三维测量研究

目的 研究老年轻度认知功能损害者的脑形态结构变化特点。方法 于1999年1月至2000年6月用脑磁共振显像（MRI）三维测量法组织分割和体积测量分析技术,检查有轻度认知功能损害的老年人21例（MCI组）和认知功能正常的老年人29名（NC组）。结果 （1）MRI测量：与NC组相比,MCI组的颅内总体积少5．2％,灰质体积少8．8％,灰质百分比少3．9％,总脑脊液多12．3％,两组差异有显著或非显著性（P＜0．05或P＜0．01）。（2）多元逐步判别分析：脑灰质和侧脑室体积具有非常显著性判别意义（P＜0．01）,两组判别总正确率为74．5％。结论 MRI三维测量有助于了解老年轻度认知功能损害者的脑部形态结构的改变。     

Neurocognitive Functioning in Overweight and Obese Patients With Bipolar Disorder: Data From the Systematic Treatment Optimization Program for Early Mania (STOP-EM)

Objective

Obesity is frequent in people with bipolar I disorder (BD I) and has a major impact on the course of the illness. Although obesity negatively influences cognitive function in patients with BD, its impact in the early phase of the disorder is unknown. We investigated the impact of overweight and obesity on cognitive functioning in clinically stable patients with BD recently recovered from their first manic episode.

Method:

Sixty-five patients with BD (25 overweight or obese and 40 normal weight) recently remitted from a first episode of mania and 37 age- and sex-matched healthy control subjects (9 overweight or obese and 28 normal weight) were included in this analysis from the Systematic Treatment Optimization Program for Early Mania (commonly referred to as STOP-EM). All subjects had their cognitive function assessed using a standard neurocognitive battery. We compared cognitive function between normal weight patients, overweight–obese patients, and normal weight healthy control subjects.

Results:

There was a negative affect of BD diagnosis on the domains of attention, verbal memory, nonverbal memory, working memory, and executive function, but we were unable to find an additional effect of weight on cognitive functioning in patients. There was a trend for a negative correlation between body mass index and nonverbal memory in the patient group.

Conclusions:

These data suggest that overweight–obesity does not negatively influence cognitive function early in the course of BD. Given that there is evidence for a negative impact of obesity later in the course of illness, there may be an opportunity to address obesity early in the course of BD.     

Neuropsychological functioning and MRI signal hyperintensities in geriatric depression

OBJECTIVE: The purpose of this study was to examine the relationship between signal hyperintensities--a probable marker of underlying pathology--on T2-weighted magnetic resonance brain scans and neuropsychological test findings in elderly depressed and normal subjects. METHOD: Elderly subjects with a DSM-III-R diagnosis of major depression (N=41) and normal elderly comparison subjects (N=38) participated in a magnetic resonance imaging study (1.0-T) of signal hyperintensities in periventricular, deep white matter, and subcortical gray matter. Hard copies of scans were rated in random order by research psychiatrists blind to diagnosis; the modified Fazekas hyperintensity rating scale was used. Cognitive performance was independently assessed with a comprehensive neuropsychological battery. Clinical and demographic differences between groups were assessed by t tests and chi-square analysis. Relationships between neuropsychological performance and diagnosis and hyperintensities and their interaction were analyzed by using analysis of covariance, with adjustment for age and education. RESULTS: Elderly depressed subjects manifested poorer cognitive performance on several tests than normal comparison subjects. A significant interaction between hyperintensity location/severity and presence/absence of depression on cognitive performance was found: depressed patients with moderate-to-severe deep white matter hyperintensities demonstrated worse performance on general and delayed recall memory indices, executive functioning and language testing than depressed patients without such lesions and normal elderly subjects with or without deep white matter changes. CONCLUSIONS: Findings validate cognitive performance decrements in geriatric depression and suggest possible neuroanatomic vulnerabilities to developing particular neuropsychological dysfunction in depressed subjects.     

Parahippocampal volume deficits in subjects with aging-associated cognitive decline

OBJECTIVE: Neuropathological evidence suggests that the earliest changes in Alzheimer's disease selectively affect the parahippocampal regions of the brain. This study was conducted to determine if otherwise healthy elderly subjects with mild cognitive impairment had structural volume deficits affecting the parahippocampal gyrus. METHOD: Magnetic resonance imaging (MRI) was used to compare global and regional brain volumes in 21 subjects with mild cognitive deficits defined according to the criteria for aging-associated cognitive decline, 22 cognitively intact comparison subjects, and 12 patients with Alzheimer's disease. RESULTS: Compared with the cognitively intact subjects, the subjects with aging-associated cognitive decline had a significantly smaller mean volume of the right parahippocampal gyrus. The subjects with aging-associated cognitive decline had a mean parahippocampal volume that was intermediate between that of the Alzheimer's disease patients and that of the cognitively intact subjects. CONCLUSIONS: Parahippocampal atrophy underlies the observed cognitive deficits in aging-associated cognitive decline. These findings support the hypothesis that aging-associated cognitive decline represents a preclinical stage of Alzheimer's disease.     

Dopamine-related frontostriatal abnormalities in obesity and binge-eating disorder: emerging evidence for developmental psychopathology

Obesity and binge-eating disorder (BED) frequently arise in adolescence, which is a critical developmental time period where self-regulatory processes are formed. Indeed, both obesity and BED are thought to arise partly due to deficits in self-regulatory processes (i.e. lack of inhibitory control to overeat or binge). Recent neuroimaging studies have implicated the frontal cortex, a brain region involved in regulating inhibitory-control, and the striatum, which is thought to be involved in food reward, satiety and pleasure, in mediating responses to food cues and feeding in normal-weight individuals as well as obese and BED subjects. Intriguingly, frontostriatal circuits have been observed to be preferentially modulated in obese adults and similar associations have been observed in obese/overweight adolescents. Furthermore, brain dopamine (DA) is selectively altered in striatum in obese relative to normal-weight individuals, and frontostriatal regions constitute a major component of DA circuitry. The aim of this review will be to present the main findings from neuroimaging studies in obese and BED adults and adolescents, as these relate to frontostriatal circuitry, and to emphasize the potential for using functional neuroimaging in both humans and animals with the scope of obtaining information on developmental and molecular contributions to obesity and BED.     

Imaging studies and APOE genotype in persons at risk for Alzheimer’s disease

Many studies have investigated APOE-related differences in cerebral structure, blood flow, metabolism, and activation in an attempt to detect early brain changes in subjects at risk for Alzheimer’s disease (AD). Structural magnetic resonance imaging studies have produced conflicting results, with some failing to detect APOE-related differences and others suggesting that ε4 carriers have more pronounced atrophy, particularly at medial temporal structures. All functional imaging studies done during rest in middle-aged and elderly subjects have found decreased cerebral metabolism for ε4 carriers (mostly in areas that usually are affected by AD), and some have reported faster cerebral metabolic reductions over time. Areas with decreased resting cerebral perfusion and metabolism, in addition to other areas with increased perfusion, have been reported in young ε4 carriers. Imaging studies done during the performance of various cognitive tasks in middle-aged and elderly subjects, and a single study in young subjects, have produced mixed results with regionally nonspecific increased, decreased, or nondifferential APOE-related activations depending on the cognitive task used. APOE-related findings in imaging studies of nondemented subjects may be the result of incipient AD pathologic changes or of genetic heterogeneity in brain structure and function.     

New insights into the brain involvement in patients with Crohn’s disease: a voxel‐based morphometry study

Background Crohn’s disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. Recently, brain morphological abnormalities in the pain matrix were found in patients with chronic pain disorders including irritable bowel syndrome. To investigate potential structural brain changes associated with CD, we used magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray matter (GM) volumes correlated with disease duration. Methods Eighteen CD patients in remission and 18 healthy controls underwent structural MRI. Voxel‐based morphometry (VBM) is a fully automated technique allowing identification of regional differences in the amount of GM enabling an objective analysis of the whole brain between groups of subjects. VBM was used for comparisons and correlation analysis. Key Results With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. Conclusions & Inferences Crohn’s disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders.     

Association between obesity and depression: evidence from a longitudinal sample of the elderly in Taiwan

Objectives: Obesity has been identified as an epidemic worldwide. In Taiwan, the highest prevalence of obesity is observed in adults age ≥65. This article investigates the effects of body weight status on the likelihood of depression among the elderly in Taiwan.

Method: A longitudinal sample of the elderly (1351 males and 1165 females) interviewed in both the 1999 and 2003 Surveys of Health and Living Status of the Elderly in Taiwan is used. A random effect logit model is estimated to examine the effects of body weight status, lifestyle, and socio-demographic characteristics on the likelihood of depression.

Results: About 10.4% of the elderly men are overweight and 13.4% are obese in 2003. A higher prevalence of obesity is found among elderly women, with 19.3% being overweight and 26.4% obese. Elderly men who are underweight are more likely to be depressed (odds ratio; OR?=?2.36) than those from other weight categories, while overweight and obese women are less likely to be depressed (ORs?=?0.72 and 0.61) than elderly women of the normal weight category.

Conclusions: In contrast to most findings for the Western countries, a negative association between obesity and depression of the elderly is evident in Taiwan. The different findings between Western and Asian countries may be due to the cultural differences. Unlike the Western countries that stigmata are attached to excessive overweight, being overweight is not a symbol of unhealthiness because only the wealthy can afford to eat more and put on more weight in the Chinese society.     

Functional changes in the activity of brain regions underlying emotion processing in the elderly

Aging is associated with a decline in both cognitive and motor abilities that reflects deterioration of underlying brain circuitry. While age-related alterations have also been described in brain regions underlying emotional behavior (e.g., the amygdala), the functional consequence of such changes is less clear. To this end, we used blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) to explore age-related changes in brain regions underlying emotion processing. Twelve young (age <30 years) and 14 elderly subjects (age >60 years) were studied with BOLD fMRI during a paradigm that involved perceptual processing of fearful and threatening stimuli. Consistent with previous reports, direct group comparisons revealed relatively increased BOLD fMRI responses in prefrontal cortical regions, including Broca's area, and relatively decreased responses in the amygdala and posterior fusiform gyri in elderly subjects. Importantly, additional analyses using an elderly-specific brain template for spatial normalization of the elderly BOLD fMRI data confirmed these divergent regional response patterns. While there was no difference between groups in accuracy on the task, elderly subjects were significantly slower (delayed reaction times) in performing the task. Our current data suggest that elderly subjects engage a more distributed neocortical network during the perceptual processing of emotional facial expressions. In light of recent converging data from two other studies, our observed effects may reflect age-related compensatory responses and/or alternative strategies in processing emotions, as the elderly appear to engage cognitive/linguistic systems in the context of reduced sensory and/or limbic responses.     

Concordance and Discordance Between Brain Perfusion and Atrophy in Frontotemporal Dementia

The aim of this study was to determine if a dissociation between reduced cerebral perfusion and gray matter (GM) atrophy exists in frontotemporal dementia (FTD). The study included 28 patients with FTD and 29 cognitive normal (CN) subjects. All subjects had MRI at 1.5 T, including T1-weighted structural and arterial spin labeling (ASL) perfusion imaging. Non-parametric concordance/discordance tests revealed that GM atrophy without hypoperfusion occurs in the premotor cortex in FTD whereas concordant GM atrophy and hypoperfusion changes are found in the right prefrontal cortex and bilateral medial frontal lobe. The results suggest that damage of brain function in FTD, assessed by ASL perfusion, can vary regionally despite widespread atrophy. Detection of discordance between brain perfusion and structure in FTD might aid diagnosis and staging of the disease.     

Chronic exposure to carbon monoxide in two elderly patients using a kotatsu,a traditional Japanese charcoal‐based heater

We report on two elderly patients with cognitive impairments, for whom chronic carbon monoxide (CO) exposure was suspected based on elevated carboxyhaemoglobin levels in their serum. On their initial visits, cognitive impairment and brain magnetic resonance imaging findings in both patients were compatible with the diagnosis of Alzheimer's‐type dementia. However, after discontinuation of the use of a kotatsu, a charcoal‐based heater, their serum carboxyhaemoglobin levels normalized and their physical symptoms resolved. Their cognitive function also slightly improved. The causal relationship between physical symptoms and cognitive impairment after chronic CO poisoning is uncertain; however, it is possible that chronic exposure to low CO levels exacerbated the clinical manifestation in our patients.     

Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis

Whilst obesity is associated with a higher risk of cognitive impairment, the influence of weight loss on cognitive function in obese/overweight people is equivocal. We conducted a meta-analysis of randomized controlled trials (RCTs) and longitudinal studies evaluating the influence of voluntary weight loss on cognitive function in obese/overweight individuals. Articles were acquired from a systematic search of major databases from inception till 01/2016. A random effect meta-analysis of weight loss interventions (diet, physical activity, bariatric surgery) on different cognitive domains (memory, attention, executive functions, language and motor speed) was conducted. Twenty studies (13 longitudinal studies = 551 participants; 7 RCTs = 328 treated vs. 140 controls) were included. Weight loss was associated with a significant improvement in attention and memory in both longitudinal studies and RCTs, whereas executive function and language improved in longitudinal and RCT studies, respectively. In conclusion, intentional weight loss in obese/overweight people is associated with improvements in performance across various cognitive domains. Future adequately powered RCTs are required to confirm/refute these findings.     

Midlife obesity and trajectories of brain volume changes in older adults

Although obesity has been linked to structural brain changes, little is known about its associations with the rates of brain atrophy. We examined associations between global (BMI) and central (waist circumference) midlife obesity and subsequent trajectories of regional brain atrophy in 152 individuals [M (age) = 69 ± 7.8] prospectively followed through the Baltimore Longitudinal Study of Aging; 21 individuals became impaired during follow-up. We report no associations (P > 0.05) between either global or central midlife obesity and subsequent rates of regional brain volume changes against a background of age-related atrophy in older individuals who remained nondemented. When looking at the entire sample, greater decline was observed in the volume of gray matter, precuneus, cingulate and orbito-frontal gyri for globally obese (P < 0.03), even though only data up to the point of dementia diagnosis were included in the analyses (i.e., while still considered clinically normal). Moreover, when trajectories of regional volume changes were examined across the range of BMI and waist circumference values instead of employing a cut-off point to define obesity, a different pattern of results emerged. Overall, our results suggest that midlife obesity may be an important modifier of brain atrophy in individuals who are developing cognitive impairment and dementia, while it has little effect on structural brain integrity in nondemented older adults. Moreover, the discrepancies in findings between studies may be in part due to participant sampling and methodological differences. Hum Brain Mapp 33:2204-2210, 2012. Published 2011 Wiley Periodicals, Inc.     

Posttraumatic stress disorder and body mass index in military veterans. Preliminary findings

Introduction: Current management of posttraumatic stress disorder (PTSD) focuses on the psychiatric parameters of this condition. Little has been written about co-morbid overweight and obesity in PTSD. Methods: We used the database of the recently constituted PTSD program at the Hunter Holmes McGuire Veterans Affairs Medical Center in Richmond, Virginia to assess and better understand the prevalence and severity of overweight and obesity among military veterans with PTSD. Variables assessed included age, decade of life, height, weight, sex, race, and severity and chronicity of PTSD. We used PTSD CheckList-Military Version (PCL-M) to assess current complaints and service-connected disability (SCD) to estimate the long-term severity of PTSD. Results: Of the 221 male veterans extracted from our PTSD database for purposes of this study, 144 (65.2%) were in the age range of 50 to 59 years consistent with Vietnam veterans dominating our study population. Their mean body mass index (BMI) was 30.2+/-5.8 kg/m(2) placing the typical veteran in the obese range. Far exceeding the current US population rate of 64.5%, 82.8% of our study population was either overweight or obese. Our sample had BMI measurements greater than those reported for non-PTSD veterans and also BMI measurements reported in the literature for veterans with PTSD. Current (PCL-M) and long-term (SCD) markers of PTSD did not relate to obesity. Conclusions: The prevalence of overweight and obesity among our veterans with PTSD far exceeded current US population findings and those of other veteran groups with and without PTSD. PTSD symptoms, whether assessed acutely or chronically, did not explain our findings. Prospective studies of PTSD and comorbidity are needed using larger study populations to better understand the relationships among PTSD, stress, and obesity.     

Neuroanatomical correlates of depression and apathy in Parkinson's disease: magnetic resonance imaging studies

Depression and apathy are among the most common neuropsychiatric disturbances in Parkinson's disease (PD), and among the most important factors associated with a poor quality of life. However, their neural bases remain unclear. The results of the magnetic resonance imaging (MRI) studies on depression in PD differ dramatically. Some of them proposed a role of morphologic changes in the mediodorsal thalamus. In contrast to previous voxel-based morphometry (VBM) data, our study did not confirm a decrease in gray matter (GM) density in any brain region of depressed PD patients. Instead, a more severe white matter (WM) loss in the right frontal lobe was found, including the anterior cingulate bundle and the inferior orbitofrontal (OF) region. We suggested that the negative correlation between the severity of depression and WM density in the right OF region reinforces the hypothesis of depression in PD as a "disconnection syndrome". Only one MRI study using VBM found that high apathy scores correlated with low GM density values in the right (posterior) cingulate gyrus and the bilateral inferior frontal gyrus, in line with the findings in Alzheimer's disease and elderly adults with major depression.     

The Alzheimer's Disease Neuroimaging Initiative: Progress report and future plans

The Alzheimer's Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year research project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer's disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD.     

Impaired autonomic control of heart rate and blood pressure in obesity: role of age and of insulin-resistance

The objectives of this study were to investigate cardiac and peripheral autonomic nervous system changes in normotensive overweight or obese subjects and the possible relation between these changes and insulin resistance independent of age. The authors used spectral analysis to measure simultaneously the short-term variability of heart rate (HR) and blood pressure (BP) using a Finapres device, in 67 normotensive over-weight or obese patients (age 37±12 y, body mass index [BMI]=37±9 kg/m²) and 45 never-obese subjects (controls; age 41±13 y, BMI 22±2 kg/m²). The spectral density was determined in three situations: subjects in the supine position, spontaneously breathing; subjects in the supine with controlled breathing; and subjects standing. The insulin sensitivity of overweight and obese subjects was determined from homeostatic model assessment (HOMA). The variability of normalized low-frequency (LF) spectral analysis of both HR and BP was lower in overweight or obese subjects than in controls, in the supine and standing positions (p<0.01). Normalized LF spectral analysis was negatively correlated to BMI independent of age, whatever the position. Homeostatic model assessment values were negatively correlated to the normalized LF spectral of HR, systolic BP and diastolic BP, in the standing position independent of BMI and age (p<0.05). Normalized high frequency (HF) of HR during controlled breathing decreased with age but not with BMI. In normotensive overweight or obese subjects, changes in sympathetic nervous system modulation are strongly correlated to insulin resistance. Decreased HR and BP variability could partly account for the higher cardiovascular risk and incidence of sudden death in obese persons.