Lack of association between cortical amyloid deposition and glucose metabolism in early stage Alzheimer´s disease patients

Abstract Background Beta amyloid (Aβ) causes synaptic dysfunction leading to neuronal death. It is still controversial if the magnitude of Aβ deposition correlates with the degree of cognitive impairment. Diagnostic imaging may lead to a better understanding the role of Aβ in development of cognitive deficits. The aim of the present study was to investigate if Aβ deposition in the corresponding brain region of early stage Alzheimer´s disease (AD) patients, directly correlates to neuronal dysfunction and cognitive impairment indicated by reduced glucose metabolism. Patients and methods In 30 patients with a clinical phenotype of AD and amyloid positive brain imaging, 2-[18F] fluoro-2-deoxy-d-glucose (FDG) PET/CT was performed. We extracted the average [18F] flutemetamol (Vizamyl) uptake for each of the 16 regions of interest in both hemispheres and computed the standardized uptake value ratio (SUVR) by dividing the Vimazyl intensities by the mean signal of positive and negative control regions. Data were analysed using the R environment for statistical computing and graphics. Results Any negative correlation between Aβ deposition and glucose metabolism in 32 dementia related and corresponding brain regions in AD patients was not found. None of the correlation coefficient values were statistically significant different from zero based on two-sided p- value. Conclusions Regional Aβ deposition did not correlate negatively with local glucose metabolism in early stage AD patients. Our findings support the role of Aβ as a valid biomarker, but does not permit to conclude that Aβ is a direct cause for an aberrant brain glucose metabolism and neuronal dysfunction.

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The role of FDG PET/CT or PET/MRI in assessing response to neoadjuvant therapy for patients with borderline or resectable pancreatic cancer: a systematic literature review

Annals of Nuclear Medicine ◽

10.1007/s12149-021-01629-0 ◽

2021 ◽

Author(s):

Laura Evangelista ◽

Pietro Zucchetta ◽

Lucia Moletta ◽

Simone Serafini ◽

Gianluca Cassarino ◽

...

Keyword(s):

Neoadjuvant Therapy ◽

Fdg Pet ◽

Standardized Uptake Value ◽

Response To Therapy ◽

Ductal Adenocarcinoma ◽

Resectable Pancreatic Cancer ◽

Number Of Patients ◽

Pet Ct ◽

Fdg Pet Ct

AbstractThe aim of the present systematic review is to examine the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) associated with computed tomography (CT) or magnetic resonance imaging (MRI) in assessing response to preoperative chemotherapy or chemoradiotherapy (CRT) for patients with borderline and resectable pancreatic ductal adenocarcinoma (PDAC). Three researchers ran a database query in PubMed, Web of Science and EMBASE. The total number of patients considered was 488. The most often used parameters of response to therapy were the reductions in the maximum standardized uptake value (SUVmax) or the peak standardized uptake lean mass (SULpeak). Patients whose SUVs were higher at the baseline (before CRT) were associated with a better response to therapy and a better overall survival. SUVs remaining high after neoadjuvant therapy correlated with a poor prognosis. Available data indicate that FDG PET/CT or PET/MRI can be useful for predicting and assessing response to CRT in patients with resectable or borderline PDAC.

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Prognostic value of the maximum standardized uptake value of pre-treatment primary lesions in small-cell lung cancer on 18F-FDG PET/CT: a meta-analysis

Acta Radiologica ◽

10.1177/0284185117745907 ◽

2017 ◽

Vol 59 (9) ◽

pp. 1082-1090 ◽

Cited By ~ 9

Author(s):

Dongyong Zhu ◽

Yanfang Wang ◽

Lisha Wang ◽

Jie Chen ◽

Sama Byanju ◽

...

Keyword(s):

Fdg Pet ◽

Meta Analysis ◽

Standardized Uptake Value ◽

Small Cell Lung ◽

Prognostic Role ◽

Pet Ct ◽

18F Fdg ◽

Pre Treatment ◽

Fdg Pet Ct

Background 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has been widely used in clinical practice. However, the prognostic value of the pre-treatment standardized uptake value (SUV) for patients with small-cell lung cancer (SCLC) remains controversial. Purpose To investigate the prognostic role of pre-treatment 18F-FDG PET on SCLC patients by meta-analysis. Material and Methods Extensive literature searches of the PubMed, EMBASE, Web of Science, and Cochrane Library databases were conducted to identify literature published until 5 May 2017. Comparative analyses of the pooled hazard ratios (HRs) for event-free survival (EFS) and overall survival (OS) were performed to assess their correlations with the pre-treatment maximum SUV (SUVmax). Either the fixed- or the random-effects model was adopted, depending on the heterogeneity observed across the studies. Subgroup analyses were performed to assess the robustness of the results. Results Twelve studies with 1062 patients were included. The pooled HR for OS of 11 studies was 1.13 (95% confidence interval [CI] = 1.05–1.22; P = 0.001; I2 = 0%) and the pooled HR for EFS of nine studies was 1.09 (95% CI = 1.02–1.17; P = 0.014; I2 = 0%), indicating that patients with high SUVs may have poorer prognoses. Begg’s test detected no significant publication bias. The prognostic role of the SUVmax remained similar in the subgroup analyses. Conclusion Our meta-analysis indicated that the pre-treatment SUVmax of primary lesions can be an important prognostic factor for OS and EFS in patients with SCLC. A high SUVmax may indicate poorer prognosis.

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Diagnostic role of 11C-Pittsburgh compound B retention patterns and glucose metabolism by fluorine-18-fluorodeoxyglucose PET/CT in amnestic and nonamnestic mild cognitive impairment patients

Nuclear Medicine Communications ◽

10.1097/mnm.0000000000000569 ◽

2016 ◽

Vol 37 (11) ◽

pp. 1189-1196 ◽

Cited By ~ 6

Author(s):

Julio F. Jiménez-Bonilla ◽

Ignacio Banzo ◽

María De Arcocha-Torres ◽

Remedios Quirce ◽

Isabel Martínez-Rodríguez ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Glucose Metabolism ◽

Pittsburgh Compound B ◽

Pet Ct ◽

Diagnostic Role ◽

Fluorodeoxyglucose Pet ◽

Fluorine 18 Fluorodeoxyglucose

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Altered Neurovascular Coupling in Subcortical Ischemic Vascular Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.598365 ◽

2021 ◽

Vol 13 ◽

Author(s):

Xiaoshuang Liu ◽

Runtian Cheng ◽

Li Chen ◽

Junwei Gong ◽

Tianyou Luo ◽

...

Keyword(s):

Cognitive Impairment ◽

Vascular Disease ◽

Early Stage ◽

Neurovascular Coupling ◽

Brain Regions ◽

Middle Temporal Gyrus ◽

Precentral Gyrus ◽

Neuropsychological Assessments ◽

Left Insula ◽

Normal Controls

Patients with subcortical ischemic vascular disease (SIVD) exhibit a high risk of cognitive impairment that might be caused by neurologic deficits and vascular injuries. However, the mechanism remains unknown. In current study, 24 normal controls (NC) and 54 SIVD patients, including 26 SIVD patients with no cognitive impairment (SIVD-NCI) and 28 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the resting-state functional MRI (rs-fMRI) and neuropsychological assessments. We combined regional homogeneity (ReHo) and cerebral blood flow (CBF) by using the global ReHo-CBF correlations coefficient and the ReHo/CBF ratio to detect the inner link between neuronal activity and vascular responses. Correlations between the ReHo/CBF ratio and neuropsychological assessments were explored in patients with SIVD. As a result, we identified significantly decreased global ReHo-CBF coupling in the SIVD-NCI group and SIVD- MCI group with respect to the NC. The SIVD-MCI group showed more serious decoupling of the global ReHo-CBF correlation. We also found a significantly abnormal ReHo/CBF ratio predominantly located in cognitive-related brain regions, including the left insula, right middle temporal gyrus, right precuneus, left precentral gyrus, and left inferior parietal lobule but not the supramarginal and angular gyri. The SIVD-MCI group showed more severe disorders of neurovascular coupling than the other two groups. Moreover, the ReHo/CBF ratio in the left precentral gyrus of the SIVD-NCI group exhibited a positive correlation with the MMSE scores. These findings suggested that patients with SIVD show abnormal neurovascular coupling at the early stage of the disease and during disease development. It might be associated with disease severity and cognitive impairment. Neurovascular decoupling in brain may be a possible neuropathological mechanism of SIVD.

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Rewiring of the Serotonin System in Major Depression

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.802581 ◽

2021 ◽

Vol 12 ◽

Author(s):

Faranak Vahid-Ansari ◽

Paul R. Albert

Keyword(s):

Mental Illness ◽

Cognitive Impairment ◽

Major Depression ◽

Selective Serotonin Reuptake Inhibitors ◽

Chronic Treatment ◽

Brain Regions ◽

Synaptic Organization ◽

Serotonin System ◽

The Brain

Serotonin is a key neurotransmitter that is implicated in a wide variety of behavioral and cognitive phenotypes. Originating in the raphe nuclei, 5-HT neurons project widely to innervate many brain regions implicated in the functions. During the development of the brain, as serotonin axons project and innervate brain regions, there is evidence that 5-HT plays key roles in wiring the developing brain, both by modulating 5-HT innervation and by influencing synaptic organization within corticolimbic structures. These actions are mediated by 14 different 5-HT receptors, with region- and cell-specific patterns of expression. More recently, the role of the 5-HT system in synaptic re-organization during adulthood has been suggested. The 5-HT neurons have the unusual capacity to regrow and reinnervate brain regions following insults such as brain injury, chronic stress, or altered development that result in disconnection of the 5-HT system and often cause depression, anxiety, and cognitive impairment. Chronic treatment with antidepressants that amplify 5-HT action, such as selective serotonin reuptake inhibitors (SSRIs), appears to accelerate the rewiring of the 5-HT system by mechanisms that may be critical to the behavioral and cognitive improvements induced in these models. In this review, we survey the possible 5-HT receptor mechanisms that could mediate 5-HT rewiring and assess the evidence that 5-HT-mediated brain rewiring is impacting recovery from mental illness. By amplifying 5-HT-induced rewiring processes using SSRIs and selective 5-HT agonists, more rapid and effective treatments for injury-induced mental illness or cognitive impairment may be achieved.

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A Personalized Computer-Aided Diagnosis System for Mild Cognitive Impairment (MCI) Using Structural MRI (sMRI)

Sensors ◽

10.3390/s21165416 ◽

2021 ◽

Vol 21 (16) ◽

pp. 5416

Author(s):

Fatma El-Zahraa A. El-Gamal ◽

Mohammed Elmogy ◽

Ali Mahmoud ◽

Ahmed Shalaby ◽

Andrew E. Switala ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Neurodegenerative Disorder ◽

Early Stage ◽

Brain Regions ◽

Computer Aided Diagnosis ◽

Cortical Region ◽

Diagnosis System ◽

Computer Aided ◽

Aided Diagnosis

Alzheimer’s disease (AD) is a neurodegenerative disorder that targets the central nervous system (CNS). Statistics show that more than five million people in America face this disease. Several factors hinder diagnosis at an early stage, in particular, the divergence of 10–15 years between the onset of the underlying neuropathological changes and patients becoming symptomatic. This study surveyed patients with mild cognitive impairment (MCI), who were at risk of conversion to AD, with a local/regional-based computer-aided diagnosis system. The described system allowed for visualization of the disorder’s effect on cerebral cortical regions individually. The CAD system consists of four steps: (1) preprocess the scans and extract the cortex, (2) reconstruct the cortex and extract shape-based features, (3) fuse the extracted features, and (4) perform two levels of diagnosis: cortical region-based followed by global. The experimental results showed an encouraging performance of the proposed system when compared with related work, with a maximum accuracy of 86.30%, specificity 88.33%, and sensitivity 84.88%. Behavioral and cognitive correlations identified brain regions involved in language, executive function/cognition, and memory in MCI subjects, which regions are also involved in the neuropathology of AD.

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Evaluation of Imaging Windows for Tau PET Imaging Using 18F-PI2620 in Cognitively Normal Individuals, Mild Cognitive Impairment, and Alzheimer’s Disease Patients

Molecular Imaging ◽

10.1177/1536012120947582 ◽

2020 ◽

Vol 19 ◽

pp. 153601212094758 ◽

Cited By ~ 1

Author(s):

Chanisa Chotipanich ◽

Monchaya Nivorn ◽

Anchisa Kunawudhi ◽

Chetsadaporn Promteangtrong ◽

Natphimol Boonkawin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Standardized Uptake Value ◽

Brain Regions ◽

Post Injection ◽

Cognitively Normal ◽

Scanning Time ◽

Normal Individuals

Background: The study aimed to evaluate the appropriate uptake-timing in cognitively normal individuals, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) patients, using 18F-PI 2620 dynamic PET acquisition. Methods: Thirty-four MCI patients, 6 AD patients, and 24 cognitively normal individuals were enrolled in this study. A dynamic 18F-PI 2620 PET study was conducted at 30-75 minutes post-injection in these groups. Co-registration was applied between the dynamic acquisition PET and T1-weighted MRI to delineate various cortical regions. The standardized uptake value ratio (SUVR) was used for quantitative analysis. P-mod software with the Automated Anatomical Labeling (AAL)-merged atlas was employed to generate automatic volumes of interest for 11 brain regions. Results: The curves in most brain regions presented an average SUVR stability at 30-40 minutes post-injection in each group. The appropriate uptake-timing interval of 18F-PI 2620 was 30-75 minutes post injection for AD group and 30-40 minutes post injection for both cognitively normal individuals and MCI groups. Conclusion: Short uptake time around 30-40 minutes post-injection would be more comfortable and convenient for all patients, especially in those with dementia who were unable to stay motionless for long periods of scanning time in the scanner.

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Pretreatment [18F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2013.10.029 ◽

2014 ◽

Vol 88 (2) ◽

pp. 312-318 ◽

Cited By ~ 30

Author(s):

Vimoj J. Nair ◽

Robert MacRae ◽

Abby Sirisegaram ◽

Jason R. Pantarotto

Keyword(s):

Positron Emission Tomography ◽

Early Stage ◽

Standardized Uptake Value ◽

Small Cell ◽

Emission Tomography ◽

Small Cell Lung ◽

Risk Status ◽

Maximum Standardized Uptake Value ◽

Positron Emission

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Involvement of Cholinergic, Adrenergic, and Glutamatergic Network Modulation with Cognitive Dysfunction in Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22052283 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2283

Author(s):

Yu-Jung Cheng ◽

Chieh-Hsin Lin ◽

Hsien-Yuan Lane

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Early Stage ◽

Amyloid Β ◽

Tau Proteins ◽

And Oxidative Stress

Alzheimer’s disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. The number of AD cases has been rapidly growing worldwide. Several the related etiological hypotheses include atypical amyloid β (Aβ) deposition, neurofibrillary tangles of tau proteins inside neurons, disturbed neurotransmission, inflammation, and oxidative stress. During AD progression, aberrations in neurotransmission cause cognitive decline—the main symptom of AD. Here, we review the aberrant neurotransmission systems, including cholinergic, adrenergic, and glutamatergic network, and the interactions among these systems as they pertain to AD. We also discuss the key role of N-methyl-d-aspartate receptor (NMDAR) dysfunction in AD-associated cognitive impairment. Furthermore, we summarize the results of recent studies indicating that increasing glutamatergic neurotransmission through the alteration of NMDARs shows potential for treating cognitive decline in mild cognitive impairment or early stage AD. Future studies on the long-term efficiency of NMDA-enhancing strategies in the treatment of AD are warranted.

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