Association between Visceral Adipose Tissue Metabolism and Cerebral Glucose Metabolism in Patients with Cognitive Impairment
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ABSTRACT:
SUBMITTER: Yu M
PROVIDER: S-EPMC11242271 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description:The visceral adipose tissue (VAT) has been recognized as an endocrine organ, and VAT dysfunction could be a risk factor for Alzheimer's disease (AD). We aimed to evaluate the association of VAT metabolism with AD pathology. This cross-sectional study included 54 older subjects with cognitive impairment who underwent 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) torso positron emission tomography (PET) and 18F-florbetaben brain PET. 18F-FDG uptake in VAT on 18F-FDG PET images was used as a marker of VAT metabolism, and subjects were classified into high and low VAT metabolism groups. A voxel-based analysis revealed that the high VAT metabolism group exhibited a significantly higher cerebral amyloid-β (Aβ) burden than the low VAT metabolism group. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that 18F-FDG uptake in VAT was significantly associated with the cerebral Aβ burden (β = 0.359, p = 0.007). In conclusion, VAT metabolism was associated with AD pathology in older subjects. Our findings suggest that VAT dysfunction could contribute to AD development.
| S-EPMC8949138 | biostudies-literature
Project description:During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.
| S-EPMC8083602 | biostudies-literature
Project description:ObjectivesTo evaluate the effects of a 9-month physical activity intervention on changes in adiposity and cognitive control based on pretrial weight status (ie, healthy weight vs obese) in children.Study designParticipants included obese (n = 77) and matched healthy-weight (n = 77) preadolescents (8-9 years) who participated in a 9-month physical activity randomized controlled trial. Cognitive function was assessed with an inhibitory control task (modified flanker task).ResultsAfter the 9-month physical activity intervention, participants exhibited a reduction in adiposity. In contrast, children in the waitlist-control condition, particularly children identified as obese pretrial, gained visceral adipose tissue (P= .008). Changes in visceral adipose tissue were related to changes in cognitive performance, such that the degree of reduction in visceral adipose tissue directly related to greater gains in inhibitory control, particularly among obese intervention participants (CI -0.14, -0.04; P= .001).ConclusionsParticipation in a daily physical activity program not only reduces adiposity but also improves children's cognitive function as demonstrated by an inhibitory control task. Furthermore, these findings reveal that the benefits of physical activity to improvements in cognitive function are particularly evident among children who are obese.Trial registrationClinicalTrials.gov: NCT01334359 and NCT01619826.
| S-EPMC5541384 | biostudies-literature
Project description:BackgroundPrevious publications indicate that Alzheimer's Disease (AD) related cortical atrophy may develop in asymmetric patterns, with accentuation of the left hemisphere. Since fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide a sensitive and specific marker of neurodegenerative disease progression, we sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive persons with mild cognitive impairment (MCI) and dementia, hypothesizing asymmetric declines of cerebral glucose metabolism.MethodsUsing florbetapir PET and cerebrospinal fluid (CSF) measures to define amyloid-β (Aβ) positivity, 40 Aβ negative (Aβ-) cognitively unimpaired controls (CU; 76 ± 5y), 76 Aβ positive (Aβ+) persons with MCI (76 ± 7y) and 51 Aβ + persons with probable AD dementia (75 ± 7y) from the AD Neuroimaging Initiative (ADNI) were included in this study with baseline and 2-year follow-up FDG PET scans. The degree of lateralization of longitudinal rCMRgl declines in subjects with Aβ + MCI and AD in comparison with Aβ- CU were statistically quantified via bootstrapped lateralization indices [(LI); range - 1 (right) to 1 (left)].ResultsCompared to Aβ- CU, Aβ + MCI patients showed marked left hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric lateralization (LI: -0.33) of rCMRgl declines was found in Aβ + persons with probable AD dementia. Additional comparisons of Aβ + groups (i.e. MCI and probable AD dementia) consequently indicated right hemispheric lateralization (LI: -0.79) of stronger rCMRgl declines in dementia stages of AD. For all comparisons, voxel-based analyses confirmed significant (pFWE<0.05) declines of rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded predominant decline of memory functions in both MCI and dementia stages of AD.ConclusionsThese data indicate that in early stages, AD may be characterized by a more lateralized pattern of left hemispheric rCMRgl declines. However, metabolic differences between hemispheres appear to diminish with further progression of the disease.
| S-EPMC6084012 | biostudies-literature
Project description:Objective: This study aimed to investigate the association between cognitive impairment and cerebral haemodynamic changes in patients with chronic vertebra-basilar (VB) stenosis. Methods: Patients with severe posterior circulation VB stenosis and infarction or a history of infarction for more than 2 weeks from January 2014 to January 2015 were enrolled (n = 96). They were divided into three groups, namely, the computed tomography perfusion (CTP) normal group, the CTP compensated group, and the CTP decompensated group. Cognitive function was assessed using a validated Chinese version of the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regression models were used to identify independent risk factors for cognitive impairment. Results: The MMSE and FAB scores of patients in the CTP decompensated group were significantly lower than those of patients in the CTP normal and CTP compensated groups (all p < 0.05). The RBANS total and its domain scores, including immediate memory, visual acuity, and delayed memory, in the CTP compensated and CTP decompensated groups were significantly lower than those in the CTP normal group (all p < 0.05). Multiple regression analyses showed that CTP compensation, CTP decompensation, severe VB tandem stenosis, and multiple infarctions were independent risk factors for cognitive impairment. Conclusions: Low perfusion caused by severe VB stenosis can lead to extensive cognitive impairments in areas such as immediate memory, visual span, and delayed memory.
| S-EPMC6168951 | biostudies-other
Project description:BackgroundThe nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents.MethodsVisceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data.ResultsIn VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression.ConclusionExpression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.
| S-EPMC8258340 | biostudies-literature
Project description:BackgroundAlzheimer's disease (AD) is one of the most severe neurodegenerative diseases leading to dementia in the elderly. Cerebral atrophy and hypoperfusion are two important pathophysiological characteristics. However, it is still unknown about the area-specific causal pathways between regional gray matter atrophy, cerebral hypoperfusion, and cognitive impairment in AD patients.MethodForty-two qualified AD patients and 49 healthy controls (HC) were recruited in this study. First, we explored voxel-wise inter-group differences in gray matter volume (GMV) and arterial spin labeling (ASL) -derived cerebral blood flow (CBF). Then we explored the voxel-wise associations between GMV and Mini-Mental State Examination (MMSE) score, GMV and CBF, and CBF and MMSE to identify brain targets contributing to cognitive impairment in AD patients. Finally, a mediation analysis was applied to test the causal pathways among atrophied GMV, hypoperfusion, and cognitive impairment in AD.ResultsVoxel-wise permutation test identified that the left middle temporal gyrus (MTG) had both decreased GMV and CBF in the AD. Moreover, the GMV of this region was positively correlated with MMSE and its CBF, and CBF of this region was also positively correlated with MMSE in AD (p < 0.05, corrected). Finally, mediation analysis revealed that gray matter atrophy of left MTG drives cognitive impairment of AD via the mediation of CBF (proportion of mediation = 55.82%, β = 0.242, 95% confidence interval by bias-corrected and accelerated bootstrap: 0.082 to 0.530).ConclusionOur findings indicated suggested that left MTG is an important hub linking gray matter atrophy, hypoperfusion, and cognitive impairment for AD, and might be a potential treatment target for AD.
| S-EPMC10117777 | biostudies-literature
Project description:Introduction: The disconnection hypothesis of Alzheimer's disease (AD) is supported by growing neuroimaging and neurophysiological evidence of altered brain functional connectivity in cognitively impaired individuals. Brain functional modalities such as [18F]fluorodeoxyglucose positron-emission tomography ([18F]FDG-PET) and electroencephalography (EEG) measure different aspects of synaptic functioning, and can contribute to understanding brain connectivity disruptions in AD. Aim: This study investigated the relationship between cortical glucose metabolism and topographical EEG measures of brain functional connectivity in subjects along AD continuum. Methods: Patients diagnosed with mild cognitive impairment (MCI) and AD (n = 67), and stratified into amyloid-positive (n = 32) and negative (n = 10) groups according to cerebrospinal fluid Aβ42/40 ratio, were assessed with [18F]FDG-PET and resting-state EEG recordings. EEG-based neuroimaging analysis involved standardized low-resolution electromagnetic tomography (sLORETA), which estimates functional connectivity from cortical sources of electrical activity in a 3D head model. Results: Glucose hypometabolism in temporoparietal lobes was significantly associated with altered EEG functional connectivity of the same regions of interest in clinically diagnosed MCI and AD patients and in patients with biomarker-verified AD pathology. The correlative pattern of disrupted connectivity in temporoparietal lobes, as detected by EEG sLORETA analysis, included decreased instantaneous linear connectivity in fast frequencies and increased lagged linear connectivity in slow frequencies in relation to the activity of remaining cortex. Conclusions: Topographical EEG measures of functional connectivity detect regional dysfunction of AD-vulnerable brain areas as evidenced by association and spatial overlap with the cortical glucose hypometabolism in MCI and AD patients. Impact statement The association between glucose hypometabolism, as evidenced by [18F]FDG-PET ([18F]fluorodeoxyglucose positron-emission tomography), and altered electroencephalography (EEG) functional connectivity metrics within temporoparietal lobes provides link between synaptic, neurophysiological, and metabolic impairment in mild cognitive impairment and Alzheimer's disease patients. This study reported alterations in EEG measures of both instantaneous and lagged linear connectivity across distinct frequency bands, both of which were shown to be important for inter- and intrahemispheric communication and function of memory systems in general. EEG-based imaging of brain functional connectivity has a potential to serve as a noninvasive, low-cost, and widely available alternative in assessing synaptic and network dysfunction in cognitively impaired patients.
| S-EPMC7757561 | biostudies-literature
Project description:This study investigated the relationships between the area and metabolic activity of adipose tissue and the presence of colorectal adenoma (CRA). Our institutional review board approved the study and waived informed consent. A total of 212 subjects who underwent fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and colonoscopy for routine health check-ups were enrolled. The volumetric parameters of areas of visceral (VATav), subcutaneous (SATav), and total adipose tissue (TATav) and calculated visceral-to-subcutaneous adipose tissue ratio (VSR) and visceral-to-total adipose tissue ratio (VAR) were considered. Metabolic parameters of standardized uptake value (SUV) of visceral (vcSUVmax, vcSUVmean), subcutaneous (scSUVmax, scSUVmean), and calculated visceral-to-subcutaneous adipose tissue ratio (VSRmax, VSRmean) were considered. Anthropometric data of height, weight, body mass index (BMI), waist circumference (WC), body fat mass (BFM), skeletal muscle mass (SMM), and diverse laboratory data were also considered as variables. Sixty-six subjects were placed in the CRA group and 146 subjects in the non-CRA group. The presence of CRA was significantly correlated with older age (P? = ?.001), male sex (P? = ?.041), higher BMI (P? = ?.004), higher WC (P? = ?.001), higher BFM (P? = ?.024), higher VATav (P?<?.001), higher TATav (P? = ?.004), higher VSR (P?<?.001), higher VAR (P?<?.001), lower vcSUVmax (P? = ?.002), lower vcSUVmean (P?<?.001), and lower VSRmean (P? = ?.002). On multiple regression analysis, vcSUVmax and vcSUVmean were independently associated with the presence of CRA (P? = ?.009 and P? = ?.045). Lower glucose metabolism of visceral adipose tissue was related to the presence of CRA. Our findings identify the value of visceral metabolic dysfunction as a potential surrogate marker of elevated risk for CRA.
| S-EPMC5484200 | biostudies-literature
Project description:The current study tested the hypothesis that glucose utilization differs between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated potential mechanisms for such a finding.VAT burden correlates better with cardiovascular risk than does SAT burden. Beyond volumetric measurement, glucose uptake in adipose tissue (AT) might reflect metabolic activity and provide pathophysiologic insight and aid risk stratification.We retrospectively studied tissue-specific glucose uptake in vivo in clinically obtained whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) scans in humans. We also assessed glucose uptake in vitro, using stromal vascular cells isolated from SAT and VAT of diet-induced obese C57BL/6 mice. Quantitative polymerase chain reaction (PCR) evaluated the expression of multiple genes involved in cellular glucose metabolism, including glucose transporters (GLUT-1, -3, and -4) and hexokinases (HK-1 and -2) in SAT and VAT of obese C57BL/6 mice.We analyzed whole-body FDG-PET scans from 31 obese and 26 lean patients. VAT exhibited higher FDG uptake compared with SAT (p < 0.0001) independent of age, sex, body mass index, comorbidities, and medications. To investigate mechanisms underlying this observation, we studied glucose uptake in the stromal vascular cell fraction of AT, which is rich in inflammatory cells. Stromal vascular cells from VAT of diet-induced obese C57BL/6 mice exhibited higher glucose uptake than those from SAT (p = 0.01). Evaluation of expression of glucose transporters (GLUT-1, -3, and -4) and hexokinases (HK-1 and -2), revealed increased expression of HK-1 in VAT-derived compared with SAT-derived stromal vascular cells, and also in visceral versus subcutaneous unfractionated AT.In humans in vivo, VAT has increased glucose uptake compared with SAT, as determined noninvasively with FDG PET imaging. Differential stromal metabolic activity may be 1 mechanism underlying differences in metabolic activity of visceral and subcutaneous AT.
| S-EPMC4042675 | biostudies-literature