florbetapir-f-18 and Amyloidosis

Cardiac amyloidosis, a restrictive heart disease with high mortality and morbidity, is underdiagnosed due to limited targeted diagnostic imaging. The primary aim of this study was to evaluate the utility of (18)F-florbetapir for imaging cardiac amyloidosis.. We performed a pilot study of cardiac (18)F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of (18)F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A (18)F-florbetapir retention index (RI) was computed. Mean LV myocardial SUVs, target-to-background ratio (TBR, myocardial/blood pool SUV ratio) and myocardial-to-liver SUV ratio between 0 and 30 min were calculated.. Left and right ventricular myocardial uptake of (18)F-florbetapir were noted in all the amyloid subjects and in none of the control subjects. The RI, TBR, LV myocardial SUV and LV myocardial to liver SUV ratio were all significantly higher in the amyloidosis subjects than in the control subjects (RI median 0.043 min(-1), IQR 0.034 - 0.051 min(-1), vs. 0.023 min(-1), IQR 0.015 - 0.025 min(-1), P = 0.002; TBR 1.84, 1.64 - 2.50, vs. 1.26, IQR 0.91 - 1.36, P = 0.001; LV myocardial SUV 3.84, IQR 1.87 - 5.65, vs. 1.35, IQR 1.17 - 2.28, P = 0.029; ratio of LV myocardial to liver SUV 0.67, IQR 0.44 - 1.64, vs. 0.18, IQR 0.15 - 0.35, P = 0.004). The myocardial RI, TBR and myocardial to liver SUV ratio also distinguished the control subjects from subjects with transthyretin and those with light chain amyloid.. (18)F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis. Its role in diagnosing amyloid in other organ systems and in assessing response to therapy needs to be further studied.

Topics: Adult; Aged; Amyloid; Amyloidosis; Aniline Compounds; Biological Transport; Case-Control Studies; Diagnosis, Differential; Ethylene Glycols; Female; Heart Diseases; Humans; Male; Middle Aged; Myocardium; Organ Specificity; Pilot Projects; Positron-Emission Tomography; Prealbumin

Cardiac amyloid quantification could advance early diagnosis of amyloid cardiomyopathy (CMP) and treatment monitoring. However, current imaging tools are based on indirect measurements.. The objectives of this pilot study were to quantify myocardial. In CMP participants, median age was 74 years and 92% were men.

Topics: Aged; Amyloid; Amyloidogenic Proteins; Amyloidosis; Female; Humans; Male; Pilot Projects; Positron Emission Tomography Computed Tomography; Predictive Value of Tests

Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using. Ninety-nine patients suspected of having AD underwent. Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ. Amyloid PET using

Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Amyloidosis; Aniline Compounds; Brain; Cognitive Dysfunction; Ethylene Glycols; Humans; Positron-Emission Tomography

Cardiac amyloidosis is an important clinical entity associated with significant morbidity and mortality. Although the signs and symptoms can be apparent early in the disease course, diagnoses are often made late because of inadequate recognition. A diagnosis of cardiac amyloidosis requires careful scrutiny of a patient's symptoms, an electrocardiogram, and imaging studies, including echocardiography and magnetic resonance imaging. Further evaluation is required through the measurement of serum and urine light chains and the use of bone scintigraphy imaging to differentiate transthyretin amyloidosis from light-chain cardiac amyloidosis. The available treatments have expanded tremendously in recent years and have improved outcomes in the population with this disorder. Thus, it has become increasingly important to diagnose cardiac amyloidosis and provide timely therapies. This article will clarify the various misconceptions about cardiac amyloidosis and provide a framework for primary care providers to better identify this disease in their practice.

Topics: Amyloid Neuropathies, Familial; Amyloidosis; Aniline Compounds; Assisted Circulation; Atrial Fibrillation; Cardiac Imaging Techniques; Cardiomyopathies; Diagnosis, Differential; Echocardiography; Electrocardiography; Ethylene Glycols; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes

Multiple mononeuropathy is a rare presentation of primary (AL) amyloidosis and nerve biopsy is usually needed for diagnosis. Conventional imaging is useful to identify proximal nerve involvement but may be inadequate. We report a patient with multiple mononeuropathy whose presentation was suggestive of AL amyloid neuropathy and in whom repeated tissue biopsies were negative for amyloid (including two sensory nerves and one muscle).

Topics: Amyloid Neuropathies; Amyloidosis; Aniline Compounds; Biopsy; Ethylene Glycols; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mononeuropathies; Neurosurgical Procedures; Positron-Emission Tomography

Amyloid deposition can lead to Alzheimer disease and cerebral amyloid angiopathy. Rarely, it presents as a solitary focal deposition, primary cerebral amyloidoma, which can be misinterpreted as a neoplasm because of the "tumor-like" appearances. We present the case of a 54-year-old woman where MRI revealed a T2-hyperintense mass periventricular in the white matter with moderate contrast enhancement. Pathological investigation revealed AL (lambda) amyloidoma. F-florbetapir PET/CT was used to support the diagnosis and in follow-up. This case highlights that F-florbetapir PET/CT might play a role in the diagnostic workup of patients suggestive of cerebral amyloidoma, especially in cases where biopsy is not feasible.

Topics: Aged; Amyloidosis; Aniline Compounds; Biopsy; Ethylene Glycols; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron Emission Tomography Computed Tomography; White Matter

Measuring plasma glial fibrillary acidic protein (GFAP) alongside cortical amyloid-β (Aβ) may shed light on astrocytic changes in aging and Alzheimer's disease (AD).. To examine associations between plasma GFAP and cortical Aβ deposition in older adults across the typical aging-to-AD dementia spectrum.. We studied two independent samples from UCSF (Cohort 1, N = 50; Cohort 2, N = 37) covering the spectra of clinical severity (CDR Sum of Boxes; CDR-SB) and Aβ-PET burden. Aβ-PET was completed with either florbetapir or Pittsburgh Compound B and standardized uptake value ratios were converted to the Centiloid (CL) scale for analyses. All participants with CDR-SB > 0 were Aβ-PET positive, while clinically normal participants (CDR-SB = 0) were a mix of Aβ-PET positive and negative. Regression analyses evaluated main effect and interaction associations between plasma GFAP, Aβ-PET, and clinical severity.. In both cohorts, plasma GFAP increased linearly with Aβ-PET CLs in clinically normal older adults. In Cohort 2, which included participants with more severe clinical dysfunction and Aβ-PET burden, the association between Aβ and GFAP became curvilinear (inverted U-shape; quadratic model R2 change = 0.165, p = 0.009), and Aβ-PET interacted with CDR-SB (R2 change = 0.164, p = 0.007): older adults with intermediate functional impairment (CDR-SB = 0.5-4.0) showed a weak (negative) association between Aβ-PET CLs and plasma GFAP, while older adults with dementia (CDR-SB > 4.0) showed a strong, negative association of higher Aβ-PET CLs with lower plasma GFAP.. The relationship between astrocytic integrity and cortical Aβ may be highly dynamic, with linear, positive associations early in disease that diverge in more severe disease stages.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Amyloidogenic Proteins; Amyloidosis; Aniline Compounds; Brain; Cognitive Dysfunction; Cohort Studies; Cross-Sectional Studies; Ethylene Glycols; Female; Glial Fibrillary Acidic Protein; Humans; Male; Positron-Emission Tomography; Radiopharmaceuticals; tau Proteins; Thiazoles

Further knowledge of the pathophysiological basis for RELAPS can help understand the adverse outcomes associated with apical LS impairment.. This was a prospective study of 32 subjects (age 62 ± 7 years; 50% males) with light chain CA. All subjects underwent two-dimensional echocardiography for LS estimation and. There was a significant base-to-apex gradient in LS (-7.4 ± 3.2% vs. -8.6 ± 4.0% vs. -20.8 ± 6.6%; p < 0.0001), maximal LV wall thickness (15.7 ± 1.9 cm vs. 15.4 ± 2.9 cm vs. 10.1 ± 2.4 cm; p < 0.0001), and LV mass (74.8 ± 21.2 g vs. 60.8 ± 17.3 g vs. 23.4 ± 6.2 g; p < 0.0001). In contrast, florbetapir RI (0.089 ± 0.03 μmol/min/g vs. 0.097 ± 0.03 μmol/min/g vs. 0.085 ± 0.03 μmol/min/g; p = 0.45) and ECV (0.53 ± 0.08 vs. 0.49 ± 0.08 vs. 0.49 ± 0.07; p = 0.15) showed no significant base-to-apex gradient in the tissue concentration or proportion of amyloid infiltration, whereas markers of total amyloid load, such as total florbetapir binding (3.4 ± 1.7 μmol/min vs. 2.8 ± 1.5 μmol/min vs. 0.93 ± 0.49 μmol/min; p < 0.0001) and extracellular LV mass (40.0 ± 15.6 g vs. 30.2 ± 10.9 g vs. 11.6 ± 3.9 g; p < 0.0001), did show a marked base-to-apex gradient.. Segmental differences in the distribution of the total amyloid mass, rather than the proportion of amyloid deposits, appear to explain the marked regional differences in LS in CA. Although these 2 matrices are clearly related concepts, they should not be used interchangeably.

Topics: Aged; Amyloid; Amyloidosis; Aniline Compounds; Cardiomyopathies; Echocardiography; Ethylene Glycols; Female; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Positron-Emission Tomography; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Stroke Volume; Ventricular Function, Left

Sleep changes have been associated with increased risks of developing cognitive disturbances and Alzheimer's disease (AD). A bidirectional relation is underlined between amyloid-beta (Aß) and sleep disruptions. The sleep profile in participants at risk to develop AD is not fully deciphered. We aim to investigate sleep-wake changes with objective sleep measurements in elderly participants without cognitive impairment depending on their brain amyloid status, positive (Aß+) or negative (Aß-) based on standard absorption ratios (SUVr) positron emission tomography-florbetapir imaging.. Sixty-eight participants without cognitive impairment who have accepted to be involved in the sleep ancillary study from the InveStIGation of Alzheimer's Predictors in Subjective Memory Complainers (INSIGHT-pre AD) cohort, aiming to record sleep profile based on the analyses of an ambulatory accelerometer-based assessment (seven consecutive 24-hour periods). Neuropsychological tests were performed and sleep parameters have been individualized by actigraph. Participants also underwent a magnetic resonance imaging scan to assess their hippocampal volume. Based on SUVr PET-florbetapir imaging, two groups Aß+ and Aß- were compared.. Participants were divided into two groups: Aß+ (n = 24) and Aß- (n = 44). Except for the SUVr, the two subgroups were comparable. When looking to sleep parameters, increased sleep latency, sleep fragmentation (wake after sleep onset [WASO] score and awakenings) and worst sleep efficiency were associated with cortical brain amyloid load.. Actigraphic sleep parameters were associated with cortical brain amyloid load in participants at risk to develop AD. The detection of sleep abnormalities in those participants may be of interest to propose some preventive strategies.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Amyloidosis; Aniline Compounds; Brain; Cognitive Dysfunction; Cohort Studies; Ethylene Glycols; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Positron-Emission Tomography; Sleep

Topics: Amyloidosis; Aniline Compounds; Cardiomyopathies; Ethylene Glycols; Heart Transplantation; Humans; Lung; Male; Middle Aged; Positron-Emission Tomography; Postoperative Complications; Recurrence

Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide association studies have identified more than 20 AD risk genes. The precise mechanism through which many of these genes are associated with AD remains unknown.. To investigate the association of the top 20 AD risk variants with brain amyloidosis.. This study analyzed the genetic and florbetapir F 18 data from 322 cognitively normal control individuals, 496 individuals with mild cognitive impairment, and 159 individuals with AD dementia who had genome-wide association studies and 18F-florbetapir positron emission tomographic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective, observational, multisite tertiary center clinical and biomarker study. This ongoing study began in 2005.. The study tested the association of AD risk allele carrier status (exposure) with florbetapir mean standard uptake value ratio (outcome) using stepwise multivariable linear regression while controlling for age, sex, and apolipoprotein E ε4 genotype. The study also reports on an exploratory 3-dimensional stepwise regression model using an unbiased voxelwise approach in Statistical Parametric Mapping 8 with cluster and significance thresholds at 50 voxels and uncorrected P < .01.. This study included 977 participants (mean [SD] age, 74 [7.5] years; 535 [54.8%] male and 442 [45.2%] female) from the ADNI-1, ADNI-2, and ADNI-Grand Opportunity. The adenosine triphosphate-binding cassette subfamily A member 7 (ABCA7) gene had the strongest association with amyloid deposition (χ2 = 8.38, false discovery rate-corrected P < .001), after apolioprotein E ε4. Significant associations were found between ABCA7 in the asymptomatic and early symptomatic disease stages, suggesting an association with rapid amyloid accumulation. The fermitin family homolog 2 (FERMT2) gene had a stage-dependent association with brain amyloidosis (FERMT2 × diagnosis χ2 = 3.53, false discovery rate-corrected P = .05), which was most pronounced in the mild cognitive impairment stage.. This study found an association of several AD risk variants with brain amyloidosis. The data also suggest that AD genes might differentially regulate AD pathologic findings across the disease stages.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloidosis; Aniline Compounds; Apolipoprotein E4; ATP-Binding Cassette Transporters; Brain; Ethylene Glycols; Female; Genome-Wide Association Study; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Mutation; Positron-Emission Tomography

Amyloid imaging demonstrates the in vivo presence of amyloid-β (Aβ) deposits in the aging human brain but it is still unknown which structural forms and modifications of Aβ are detected. In Alzheimer's disease, most amyloid deposits are predominantly composed of Aβ ending at amino acid residues Val40 or Ala42. It has been reported that Aβ40 is largely restricted to neuritic plaques while Aβ42 may be deposited in amyloid plaques of all types, and is often the sole component of diffuse plaques. The distinction is important as it is mainly the neuritic plaques that correlate with cognitive impairment while diffuse plaques may be the initial type of Aβ deposited. Whether PET amyloid ligands such as florbetapir-18F (Amyvid) are partially or wholly selective for brain deposits of Aβ40 or Aβ42 is currently unknown. We compared antemortem florbetapir PET cortical/cerebellar signal intensity (SUVr) of 55 subjects with postmortem biochemical (ELISA) measurements employing specific antibodies against Aβ40 and Aβ42. Spearman's univariable correlations were significant for both Aβ40 and Aβ42, but were much stronger for Aβ42. Multiple linear regression showed significance only for Aβ42. These results suggest that florbetapir binds only weakly, if at all, to Aβ40. This may be in part due to the higher likelihood for Aβ42 to be present in a β-pleated sheet tertiary structure, or to differences between Aβ40 and Aβ42 in β-pleated sheet tertiary or quaternary structure.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Amyloidosis; Aniline Compounds; Autopsy; Brain; Ethylene Glycols; Humans; Linear Models; Peptide Fragments; Plaque, Amyloid; Positron-Emission Tomography

Patients with late-life depression may be at the preclinical stage of dementia. However, the neurodegenerative processes in late-life depression are poorly understood. This study aimed to investigate the distribution patterns of amyloid pathology and neurodegeneration in a depressive population without dementia.. Most of the control subjects (81.8%) were biomarker-negative, in contrast to the MCI MDD patients (37.5%). A relatively high proportion of the MCI MDD patients (12.5%) exhibited both amyloid positivity and hippocampal atrophy as compared to the control subjects (4.5%) and non-MCI patients (5.1%). However, a considerable proportion of the MCI MDD patients (29.2%) were categorized into the group with hippocampal atrophy alone, and negative amyloid deposition, as compared to the control subjects (0%) and non-MCI patients (5.1%).. This study highlights the expected heterogeneity of the processes of neurodegeneration in MDD patients. The diverse neurodegenerative processes may have important etiologic and therapeutic implications regarding neurodegenerative pathophysiology in late-life depression.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Amyloidosis; Aniline Compounds; Atrophy; Biomarkers; Brain Diseases; Cognitive Dysfunction; Depressive Disorder, Major; Ethylene Glycols; Female; Hippocampus; Humans; Male; Middle Aged; Neurodegenerative Diseases; Positron-Emission Tomography; Radiopharmaceuticals; Temporal Lobe

Late-life depression, even when of subsyndromal severity, has shown strong associations with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Preclinical studies have suggested that serotonin selective reuptake inhibitors (SSRIs) can attenuate amyloidogenesis. Therefore, we aimed to investigate the effect of SSRI medication on amyloidosis and grey matter volume in subsyndromal depressed subjects with MCI and AD during an interval of two years. 256 cognitively affected subjects (225 MCI/ 31 AD) undergoing [18F]-AV45-PET and MRI at baseline and 2-year follow-up were selected from the ADNI database. Subjects with a positive depression item (DEP(+); n = 73) in the Neuropsychiatric Inventory Questionnaire were subdivided to those receiving SSRI medication (SSRI(+); n = 24) and those without SSRI treatment (SSRI(-); n = 49). Longitudinal cognition (Δ-ADAS), amyloid deposition rate (standardized uptake value, using white matter as reference region (SUVRWM), and changes in grey matter volume were compared using common covariates. Analyses were performed separately in all subjects and in the subgroup of amyloid-positive subjects. Cognitive performance in DEP(+)/SSRI(+) subjects (Δ-ADAS: -5.0%) showed less deterioration with 2-year follow-up when compared to DEP(+)/SSRI(-) subjects (Δ-ADAS: +18.6%, p < 0.05), independent of amyloid SUVRWM at baseline. With SSRI treatment, the progression of grey matter atrophy was reduced (-0.9% versus -2.7%, p < 0.05), notably in fronto-temporal cortex. A slight trend towards lower amyloid deposition rate was observed in DEP(+)/SSRI(+) subjects versus DEP(+)/SSRI(-). Despite the lack of effect to amyloid PET, SSRI medication distinctly rescued the declining cognitive performance in cognitively affected patients with depressive symptoms, and likewise attenuated grey matter atrophy.

Topics: Aged; Alzheimer Disease; Amyloid; Amyloidosis; Aniline Compounds; Atrophy; Cognition; Cognitive Dysfunction; Depression; Ethylene Glycols; Female; Follow-Up Studies; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Organ Size; Positron-Emission Tomography; Radiopharmaceuticals; Selective Serotonin Reuptake Inhibitors; Superior Sagittal Sinus; Treatment Outcome

Topics: Aged; Amyloidosis; Aniline Compounds; Chemotactic Factors; Ethylene Glycols; Female; Humans; Kidney Failure, Chronic; Positron Emission Tomography Computed Tomography

We present a case of both F-FDG and F-florbetapir uptake in a biopsy-confirmed immunoglobulin light chain (AL) amyloidosis involving the peripheral nerves. AL amyloidosis is the most common cause of acquired amyloid polyneuropathy, manifesting with both sensorimotor and autonomic neuronal dysfunction. Given the overlapping MRI and FDG PET/CT appearances of several different causes of peripheral neuropathy, F-florbetapir PET/CT provides another potential tool in the imaging algorithm of these patients and may guide targeted fascicular biopsy for pathologic confirmation.

Topics: Amyloid Neuropathies; Amyloidosis; Aniline Compounds; Ethylene Glycols; Fluorodeoxyglucose F18; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed

Topics: Aged; Amyloidosis; Aniline Compounds; Echocardiography; Ethylene Glycols; Fluorine Radioisotopes; Heart Diseases; Humans; Magnetic Resonance Imaging; Male; Positron Emission Tomography Computed Tomography; Ventricular Dysfunction, Left

Topics: Amyloidosis; Aniline Compounds; Brain Diseases, Metabolic; Ethylene Glycols; Humans; Male; Middle Aged; Positron-Emission Tomography

PET amyloid imaging is increasingly used in research trials related to Alzheimer disease and has potential as a quantitative biomarker. This study had 3 objectives: first, to describe a semiautomated quantitative method that does not require subject-specific MR imaging scans for estimating F 18 Florbetapir plaque binding using 10-min PET images; second, to evaluate the method's accuracy for identifying positive and negative scans; and third, to correlate derived standardized uptake value ratios to neuropathologic measures of amyloid.. The F 18 Florbetapir PET images are initially converted to Montreal Neurologic Institute brain atlas space using an internally developed PET target F 18 Florbetapir template. Subsequently, a single mean cortical standardized uptake value ratio (mcSUVr) is calculated from the mean standardized uptake value of 6 cortical regions normalized to a reference region. Four reference regions were explored: whole cerebellum, cerebellar gray matter, pons, and centrum semiovale. The performance of the resultant mcSUVrs were evaluated in 74 young cognitively normal subjects (age < 50 y) with a negligible likelihood of amyloid β pathology, and in 59 deceased subjects with autopsy-based amyloid β neuritic plaque measure who underwent F 18 Florbetapir PET imaging before death.. Significant correlations were obtained between mcSUVrs and 3 different pathologic measures of amyloid deposition at autopsy using all 4 reference regions, with the whole-cerebellum mcSUVr correlating most strongly across pathologic measures (r = 0.71-0.75, P < 0.0001). Using the whole-cerebellum mcSUVr and a threshold mcSUVr of less than 1.10, 100% of young cognitively normal subjects were correctly classified as amyloid-negative (mcSUVr range, 0.87-1.08). Similarly, 20 of 20 autopsy-negative subjects showed mcSUVrs of 1.10 or less, whereas 38 of 39 pathology-verified amyloid-positive subjects had mcSUVrs of more than 1.10.. This semiautomated F 18 Florbetapir PET quantification method yielded mcSUVrs that significantly correlated with measures of amyloid pathology at autopsy. The method also effectively discriminated autopsy-identified amyloid-positive and -negative cases using a whole-cerebellum mcSUVr threshold of 1.10.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Amyloidogenic Proteins; Amyloidosis; Aniline Compounds; Automation; Autopsy; Brain; Cerebellum; Ethylene Glycols; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Pons; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results

Topics: Amyloidosis; Aniline Compounds; Ethylene Glycols; Female; Heart Diseases; Humans; Male; Positron-Emission Tomography