Flutemetamol

PURPOSE: Characteristic features of amyloid-PET (A), tau-PET (T), and FDG-PET (N) can serve for the A/T/N classification of neurodegenerative diseases. Recent studies showed that the early, perfusion-weighted phases of amyloid- or tau-PET recordings serve to detect cerebrometabolic deficits equally to FDG-PET, therefore providing a surrogate of neuronal injury. As such, two channels of diagnostic information can be obtained in the setting of a single PET scan. However, there has hitherto been no comparison of early-phase amyloid- and tau-PET as surrogates for deficits in perfusion/metabolism...

BACKGROUND: Beta amyloid in the brain, which was originally confirmed by post-mortem examinations, can now be confirmed in living patients using amyloid positron emission tomography (PET) tracers, and the accuracy of diagnosis can be improved by beta amyloid plaque confirmation in patients. Amyloid deposition in the brain is often associated with the expression of dementia. Hence, it is important to identify the anatomically and functionally meaningful areas of the human brain cortex surface using PET to diagnose the possibility of developing dementia...

BACKGROUND: What combination of risk factors for Alzheimer's disease (AD) are most predictive of cognitive decline in cognitively unimpaired individuals remains largely unclear. We studied associations between APOE genotype, AD-Polygenic Risk Scores (AD-PRS), amyloid-β pathology and decline in cognitive functioning over time in a large sample of cognitively unimpaired older individuals. METHODS: We included 276 cognitively unimpaired older individuals (75 ± 10 years, 63% female) from the EMIF-AD PreclinAD cohort...

Brain network dysfunction is increasingly recognised in Alzheimer's disease (AD). However, the causes of brain connectivity disruption are still poorly understood. Recently, neuroinflammation has been identified as an important factor in AD pathogenesis. Microglia participate in the construction and maintenance of healthy neuronal networks, but pro-inflammatory microglia can also damage these circuits. We hypothesised that microglial activation is independently associated with brain connectivity disruption in AD...

BACKGROUND: [18 F]flutemetamol is a PET radioligand used to image brain amyloid, but its detection of myocardial amyloid is not well-characterized. This histological study characterized binding of fluorescently labeled flutemetamol (cyano-flutemetamol) to amyloid deposits in myocardium. METHODS: Myocardial tissue was obtained post-mortem from 29 subjects with cardiac amyloidosis including transthyretin wild-type (ATTRwt), hereditary/variant transthyretin (ATTRv) and immunoglobulin light-chain (AL) types, and from 10 cardiac amyloid-free controls...

Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer. Benzothiazole derivatives have been successfully shown to target these plaques and are used in several imaging applications...

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) is an often under-recognized cause of heart failure with preserved ejection fraction. The goal of the current paper was to review imaging modalities available for detecting cardiac amyloidosis. We wished to determine what modalities are available for the diagnosis of cardiac amyloidosis and what modalities could be utilized in the future. RECENT FINDINGS: Early and delayed planar imaging of the chest currently plays a central role in the workup and diagnosis of CA...

BACKGROUND: Delaying the transition from minimal cognitive impairment to Alzheimer's dementia is a major concern in Alzheimer's disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer's dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms...

This paper proposes a novel method for the automatic quantification of amyloid positron emission tomography (PET) using the deep learning (DL)-based spatial normalization (SN) of PET images, which does not require magnetic resonance imaging (MRI) or computed tomography images of the same patient. The accuracy of the method was evaluated for three different amyloid PET radiotracers compared to MRI-parcellation-based PET quantification using FreeSurfer. Methods: A deep neural network model used for the SN of amyloid PET images was trained using 994 multicenter amyloid PET images (367 18 F-Flutemetamol and 627 18 F-Florbetaben) and the corresponding 3D MRIs of patients with Alzheimer's disease or mild cognitive impairment, and cognitively normal subjects...

BACKGROUND: Subjective cognitive decline (SCD) is a target for Alzheimer's disease prediction. Plasma amyloid-beta oligomer (AβO), the pathogenic form of Aβ in blood, has recently been proposed as a novel blood-based biomarker of AD prediction by representing brain Aβ deposition. The relationship between plasma AβO, brain Aβ deposition, and SCD in individuals with normal objective cognition has not been investigated. METHODS: In this cross-sectional study, we analyzed 126 participants with normal objective cognition...

Cerebrovascular dysfunction has been suggested as a physiomarker of Alzheimer's disease (AD)-associated neuronal degeneration, but the underlying mechanisms are still debated. Herein cerebral vasomotor reactivity (VMR, breath-hold index: BHI), metabolic activity (lobar SUVs, FDG PET MRI), amyloid load (Centiloid score, Flutemetamol PET MRI), hemispheric cortical thickness, white matter lesion load and cerebral blood flow (ASL) were studied in 43 consecutive subjects (mean age: 64 years, female 13), diagnosed with subjective cognitive impairment (SCI, n = 10), amnestic mild cognitive impairment (aMCI, n = 15), and probable Alzheimer's dementia (AD, n = 18)...

BACKGROUND: Elucidation of the mechanism of amyloid-β accumulation plays an important role in therapeutic strategies for Alzheimer's disease (AD). The aim of this study is to elucidate the relationship between the function of the blood-cerebrospinal fluid barrier (BCSFB) and the clearance of amyloid-β (Aβ). METHODS: Twenty-five normal older adult volunteers (60-81 years old) participated in this PET study for clarifying the relationship between interstitial water flow and Aβ accumulation...

BACKGROUND: The standard Centiloid (CL) method was proposed to harmonize and quantify global 18 F-labeled amyloid beta (Aβ) PET ligands using MRI as an anatomical reference. However, there is need for harmonizing and quantifying regional Aβ uptakes between ligands using CT as an anatomical reference. In the present study, we developed and validated a CT-based regional direct comparison of 18 F-florbetaben (FBB) and 18 F-flutemetamol (FMM) Centiloid (rdcCL). METHODS: For development of MRI-based or CT-based rdcCLs, the cohort consisted of 63 subjects (20 young controls (YC) and 18 old controls (OC), and 25 participants with Alzheimer's disease dementia (ADD))...

We report 18F-flutemetamol PET/CT finding in an 88-year-old man with cognitive impairment and transthyretin amyloid cardiomyopathy. Early phase PET/CT images showed significantly increased myocardial uptake, but there was no myocardial uptake in delayed phase PET/CT images. A dual-time-point amyloid PET/CT imaging may be helpful to diagnose and differentiate subtypes of amyloid cardiomyopathy in patients with suspected cardiac amyloidosis.

INTRODUCTION: Amyloid-β protein (Aβ) is one of the biomarkers for Alzheimer's disease (AD). The recent application of interhemispheric functional connectivity (IFC) in resting-state fMRI has been used as a non-invasive diagnostic tool for early dementia. In this study, we focused on the level of Aβ accumulated and its effects on the major functional networks, including default mode network (DMN), central executive network (CEN), salience network (SN), self-referential network (SRN) and sensory motor network (SMN)...

Objectives: Multiple risk loci for late-onset Alzheimer's disease (LOAD) have been identified. Type 2 diabetes (T2D) is a risk factor for cognitive decline, dementia and Alzheimer's disease (AD). We investigated the association of polygenic risk score (PRS) for LOAD with overall cognitive functioning and longitudinal decline, among older adults with T2D. Methods: The study included 1046 Jewish participants from the Israel Diabetes and Cognitive Decline (IDCD) study, aged ≥ 65 years, diagnosed with T2D, and cognitively normal at baseline...

BACKGROUND: The COVID-19 pandemic may worsen the mental health of people reporting subjective cognitive decline (SCD) and therefore their clinical prognosis. We aimed to investigate the association between the intensity of SCD and anxious/depressive symptoms during confinement and the underlying mechanisms. METHODS: Two hundred fifty cognitively unimpaired participants completed the Hospital Anxiety and Depression Scale (HADS) and SCD-Questionnaire (SCD-Q) and underwent amyloid-β positron emission tomography imaging with [18 F] flutemetamol (N = 205) on average 2...

BACKGROUND: Our aim was to investigate the discriminative value of 18 F-Flutemetamol PET in longitudinal assessment of amyloid beta accumulation in amnestic mild cognitive impairment (aMCI) patients, in relation to longitudinal cognitive changes. METHODS: We investigated the change in 18 F-Flutemetamol uptake and cognitive impairment in aMCI patients over time up to 3 years which enabled us to investigate possible association between changes in brain amyloid load and cognition over time...

Neurodegenerative dementias are characterized by the abnormal accumulation of misfolded proteins. However, its diagnostic criteria are still based on the clinical phenotype. The development of biomarkers allowed in vivo detection of pathophysiological processes. This article aims to make a non-systematic review of the use of molecular neuroimaging as a biomarker. Molecular neuroimaging is based on the use of radiotracers for image acquisition. The radiotracer most used in PET is 18F-fluorodeoxyglucose (FDG), with which it is possible to study the regional brain glucose metabolism...

BACKGROUND: There has been renewed interest in the deteriorating effects of sub-threshold amyloid-β (Aβ) accumulation in Alzheimer's disease (AD). Despite evidence suggesting a synergistic interaction between the APOE ɛ4 allele and Aβ deposition in neurodegeneration, few studies have investigated the modulatory role of this allele in sub-threshold Aβ deposition during the preclinical phase. OBJECTIVE: We aimed to explore the differential effect of the APOE ɛ4 carrier status on the association between sub-threshold Aβ deposition, cortical volume, and cognitive performance in cognitively normal older adults (CN)...