scholarly journals Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer’s subjects?

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Grazia Daniela Femminella ◽  
Nicholas R. Livingston ◽  
Sanara Raza ◽  
Thalia van der Doef ◽  
Eleni Frangou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Grey Matter ◽  
Insulin Signalling ◽  
Diabetic Patients ◽  
Grey Matter Volume ◽  
Model Assessment ◽  
Matter Volume ◽  
Peripheral Insulin Resistance ◽  
18F Fdg

Abstract Background Type 2 diabetes is a risk factor for Alzheimer’s disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects. Methods In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function. Results In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs. Conclusions In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.

scholarly journals Relationship between astrocyte reactivity, using novel 11C-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals

2021 ◽  
Author(s):  
Nicholas R Livingston ◽  
Valeria Calsolaro ◽  
Rainer Hinz ◽  
Joseph Nowell ◽  
Sanara Raza ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Temporal Lobe ◽  
Grey Matter ◽  
Amyloid Deposition ◽  
Cognitively Impaired ◽  
Grey Matter Volume ◽  
Healthy Controls ◽  
Matter Volume ◽  
Amyloid Load ◽  
18F Fdg

Post mortem neuropathology suggests that astrocyte reactivity may play a significant role in neurodegeneration in Alzheimer's disease. We explored this in vivo using multimodal PET and MRI imaging. Twenty subjects (11 older, cognitively impaired subjects and 9 age-matched healthy controls) underwent brain scanning using the novel reactive astrocyte PET tracer 11C-BU99008, 18F-FDG and 18F-florbetaben PET, and T1-weighted MRI. Differences between cognitively impaired subjects and healthy controls in voxel-wise levels of astrocyte reactivity, glucose metabolism and grey matter volume were explored, and their relationship to each other was assessed using Biological Parametric Mapping (BPM). Amyloid-positive cognitively impaired subjects showed greater brain astrocyte reactivity, except in the temporal lobe, with further increased astrocyte reactivity in Mild Cognitive Impairment compared to Alzheimer's subjects in the cingulate cortices. BPM correlations revealed regions which showed reduced 11C-BU99008 uptake in Amyloid-positive cognitively impaired subjects, such as the temporal lobe, also showed reduced 18F-FDG uptake and grey matter volume. BPM analysis also revealed a regionally-dynamic relationship between astrocyte reactivity and amyloid uptake: increased amyloid load in cortical association areas of the temporal lobe and cingulate cortices was associated with reduced astrocyte reactivity, whilst increased amyloid uptake in primary motor and sensory areas (in which amyloid load occurs later) was associated with increased astrocyte reactivity. These novel observations add to the hypothesis that while astrocyte reactivity may be triggered by early Amyloid-deposition, sustained pro-inflammatory astrocyte reactivity with greater amyloid deposition may lead to astrocyte dystrophy and amyloid-associated neuropathology such as grey matter atrophy and glucose hypometabolism.

Social cognition and brain organization in chimpanzees (Pan troglodytes) and bonobos (Pan paniscus)

2018 ◽  
Author(s):  
William D. Hopkins ◽  
Cheryl D. Stimpson ◽  
Chet C. Sherwood
Keyword(s):  
Social Cognition ◽  
Social Behaviour ◽  
Grey Matter ◽  
Species Differences ◽  
Pan Paniscus ◽  
Grey Matter Volume ◽  
Evolutionary Models ◽  
Brain Organization ◽  
Matter Volume ◽  
Cognition Sociale

Bonobos and chimpanzees are two closely relates species of the genus Pan, yet they exhibit marked differences in anatomy, behaviour and cognition. For this reason, comparative studies on social behaviour, cognition and brain organization between these two species provide important insights into evolutionary models of human origins. This chapter summarizes studies on socio-communicative competencies and social cognition in chimpanzees and bonobos from the authors’ laboratory in comparison to previous reports. Additionally, recent data on species differences and similarities in brain organization in grey matter volume and distribution is presented. Some preliminary findings on microstructural brain organization such as neuropil space and cellular distribution in key neurotransmitters and neuropeptides involved in social behaviour and cognition is presented. Though these studies are in their infancy, the findings point to potentially important differences in brain organization that may underlie bonobo and chimpanzees’ differences in social behaviour, communication and cognition. Les bonobos et les chimpanzés sont deux espèces du genus Pan prochement liées, néanmoins ils montrent des différences anatomiques, comportementales et cognitives marquées. Pour cette raison, les études comparatives sur le comportement social, la cognition et l’organisation corticale entre ces deux espèces fournissent des idées sur les modèles évolutionnaires des origines humaines. Dans ce chapitre, nous résumons des études sur les compétences socio-communicatives et la cognition sociale chez les chimpanzés et les bonobos de notre laboratoire en comparaison avec des rapports précédents. En plus, nous présentons des données récentes sur les différences et similarités d’organisation corticale du volume et distribution de la matière grise entre espèces. Nous présentons plus de résultats préliminaires sur l’organisation corticale microstructurale comme l’espace neuropile et la division cellulaire dans des neurotransmetteurs clés et les neuropeptides impliqués dans le comportement social et la cognition. Bien que ces études sont dans leur enfance, les résultats montrent des différences d’organisation corticale importantes qui sont à la base des différences de comportement social, la communication et la cognition entre les bonobos et les chimpanzés.

scholarly journals Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia

2021 ◽  
pp. jnnp-2020-323541
Author(s):  
Jessica L Panman ◽  
Vikram Venkatraghavan ◽  
Emma L van der Ende ◽  
Rebecca M E Steketee ◽  
Lize C Jiskoot ◽  
...  
Keyword(s):  
White Matter ◽  
Frontotemporal Dementia ◽  
Disease Severity ◽  
Grey Matter ◽  
Clinical Stage ◽  
Data Driven ◽  
Grey Matter Volume ◽  
Matter Volume ◽  
Mutation Carriers ◽  
Individual Disease

ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.

scholarly journals SAT0111 THE RELATIONSHIP BETWEEN THE ADMINISTRATION OF IL-6 INHIBITORS AND INSULIN RESISTANCE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 989.3-989
Author(s):  
A. Jitaru ◽  
C. Pomirleanu ◽  
M. M. Leon-Constantin ◽  
F. Mitu ◽  
C. Ancuta
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Beneficial Effect ◽  
Disease Activity ◽  
Interleukin 6 ◽  
Normal Weight ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Inflammatory Status

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly

scholarly journals Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1532
Author(s):  
Eleni Rebelos ◽  
Juha O. Rinne ◽  
Pirjo Nuutila ◽  
Laura L. Ekblad
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Cognitive Decline ◽  
Fdg Pet ◽  
Metabolic Disorders ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
Systemic Insulin Resistance ◽  
Increased Risk ◽  
18F Fdg

Imaging brain glucose metabolism with fluorine-labelled fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) has long been utilized to aid the diagnosis of memory disorders, in particular in differentiating Alzheimer’s disease (AD) from other neurological conditions causing cognitive decline. The interest for studying brain glucose metabolism in the context of metabolic disorders has arisen more recently. Obesity and type 2 diabetes—two diseases characterized by systemic insulin resistance—are associated with an increased risk for AD. Along with the well-defined patterns of fasting [18F]-FDG-PET changes that occur in AD, recent evidence has shown alterations in fasting and insulin-stimulated brain glucose metabolism also in obesity and systemic insulin resistance. Thus, it is important to clarify whether changes in brain glucose metabolism are just an epiphenomenon of the pathophysiology of the metabolic and neurologic disorders, or a crucial determinant of their pathophysiologic cascade. In this review, we discuss the current knowledge regarding alterations in brain glucose metabolism, studied with [18F]-FDG-PET from metabolic disorders to AD, with a special focus on how manipulation of insulin levels affects brain glucose metabolism in health and in systemic insulin resistance. A better understanding of alterations in brain glucose metabolism in health, obesity, and neurodegeneration, and the relationships between insulin resistance and central nervous system glucose metabolism may be an important step for the battle against metabolic and cognitive disorders.

Cerebellar Grey Matter Volume in Older Persons Is Associated with Worse Cognitive Functioning

2020 ◽  
Author(s):  
A. Buhrmann ◽  
A. M. A. Brands ◽  
J. van der Grond ◽  
C. Schilder ◽  
R. C. van der Mast ◽  
...  
Keyword(s):  
Cognitive Functioning ◽  
Older Persons ◽  
Grey Matter ◽  
Grey Matter Volume ◽  
Matter Volume

Plasma vitamin C, cholesterol and homocysteine are associated with grey matter volume determined by MRI in non-demented old people

2003 ◽  
Vol 341 (3) ◽  
pp. 173-176 ◽  
Author(s):  
L.J. Whalley ◽  
R.T. Staff ◽  
A.D. Murray ◽  
S.J. Duthie ◽  
A.R. Collins ◽  
...  
Keyword(s):  
Vitamin C ◽  
Grey Matter ◽  
Grey Matter Volume ◽  
Plasma Vitamin ◽  
Old People ◽  
Matter Volume
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