scholarly journals Functional Abnormality Associated With Tau Deposition in Alzheimer’s Disease – A Hybrid Positron Emission Tomography/MRI Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Liping Fu ◽  
Zhi Zhou ◽  
Linwen Liu ◽  
Jinming Zhang ◽  
Hengge Xie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Standardized Uptake Value ◽  
Occipital Lobe ◽  
Posterior Cingulate Cortex ◽  
Functional Abnormality ◽  
Individual Level ◽  
Positron Emission ◽  
Mri Scans ◽  
The Individual

Objective: To investigate the characteristics of tau deposition and its impact on functional connectivity (FC) in Alzheimer’s disease (AD).Methods: Hybrid PET/MRI scans with [18F]-THK5317 and neuropsychological assessments were undertaken in 26 participants with AD and 19 healthy controls (HC). The standardized uptake value ratio (SUVR) of [18F]-THK5317 PET imaging was compared between the AD and HC groups. Significant clusters that revealed higher tau deposition in the AD group compared to the HC group were selected as regions of interest (ROI) for FC analysis. We evaluated the difference in the FC between the two groups for each ROI pair. The clinical and radiological characteristics were compared between the AD patients with negative FC and AD patients with positive FC for exploratory analysis.Results: The bilateral inferior lateral temporal lobe, dorsal prefrontal cortex, precuneus, posterior cingulate cortex, hippocampus, and occipital lobe showed significantly higher [18F]-THK5317 accumulation in AD patients. Decreased FC in regions with higher SUVR was observed in AD patients, and the FC strength was negatively correlated with regional SUVR. Patients with a positive FC exhibited older ages, better cognitive performances, and a lower SUVR than patients with a negative FC.Conclusions: An impact of tau deposition was observed on FC at the individual level in AD patients. Our findings suggested that the combination of tau-PET and rs-fMRI might help predict AD progression.

scholarly journals Towards harmonizing subtyping methods for neuroimaging studies in Alzheimer’s disease

2020 ◽  
Author(s):  
Rosaleena Mohanty ◽  
Gustav Mårtensson ◽  
Konstantinos Poulakis ◽  
J-Sebastian Muehlboeck ◽  
Elena Rodriguez-Vieitez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reference Group ◽  
Group Level ◽  
Individual Level ◽  
Dementia Patients ◽  
Positron Emission ◽  
Tau Pet ◽  
The Individual

ABSTRACTBackgroundBiological subtypes in Alzheimer’s disease (AD), originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within AD. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context.MethodsWe compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive (Aβ+) AD dementia patients (reference group: 70 Aβ-healthy individuals; HC) using sMRI. Secondly, we extended and applied the subtyping methods to 53 Aβ+ prodromal AD and 30 Aβ+ AD dementia patients (reference group: 200 Aβ-HC) using both sMRI and tau PET. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed.ResultsEach individual method was replicated and the proof-of-concept was established. All methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar maps of cortical thinning and tau PET uptake, at the group level. However, large disagreements were found at the individual level.ConclusionsAlthough characteristics of subtypes may be comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for establishment of an open benchmarking framework to overcome this problem.

scholarly journals Serum MicroRNA Profiles Serve as Novel Biomarkers for the Diagnosis of Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Hui Dong ◽  
Jialu Li ◽  
Lei Huang ◽  
Xi Chen ◽  
Donghai Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Characteristic Curve ◽  
Serum Samples ◽  
Individual Level ◽  
Serum Microrna ◽  
Serum Mirnas ◽  
Potential Biomarker ◽  
Novel Biomarkers ◽  
The Individual

Alzheimer’s disease (AD) is the most common type of dementia, and promptly diagnosis of AD is crucial for delaying the development of disease and improving patient quality of life. However, AD detection, particularly in the early stages, remains a substantial challenge due to the lack of specific biomarkers. The present study was undertaken to identify and validate the potential of circulating miRNAs as novel biomarkers for AD. Solexa sequencing was employed to screen the expression profile of serum miRNAs in AD and controls. RT-qPCR was used to confirm the altered miRNAs at the individual level. Moreover, candidate miRNAs were examined in the serum samples of patients with mild cognitive impairment (MCI) and vascular dementia (VD). The results showed that four miRNAs (miR-31, miR-93, miR-143, and miR-146a) were markedly decreased in AD patients’ serum compared with controls. Receiver operating characteristic curve analysis demonstrated that this panel of four miRNAs could be used as potential biomarker for AD. Furthermore, miR-93, and miR-146a were significantly elevated in MCI compared with controls, and the panel of miR-31, miR-93 and miR-146a can be used to discriminate AD from VD. We established a panel of four serum miRNAs as a novel noninvasive biomarker for AD diagnosis.

scholarly journals Subcortical Hypermetabolism Associated With Cortical Hypometabolism Is a Common Metabolic Pattern in Patients With Anti-Leucine-Rich Glioma-Inactivated 1 Antibody Encephalitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaobin Zhao ◽  
Shaokun Zhao ◽  
Yaojing Chen ◽  
Zhanjun Zhang ◽  
Xiaotong Li ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Parietal Lobe ◽  
Statistical Parametric Mapping ◽  
Occipital Lobe ◽  
Healthy Controls ◽  
Metabolic Pattern ◽  
Individual Level ◽  
Positron Emission ◽  
Neurologic Disability ◽  
The Individual

PurposeBrain 18F-fluorodeoxyglucose positron emission tomography (FDG PET) is a sensitive technique for assisting in the diagnosis of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis. However, the common pattern of this disorder assessed by FDG PET remains unknown. The present study aimed to explore the glucose metabolic patterns of this disorder based on PET voxel analysis.MethodsThis retrospective study enrolled 25 patients with anti-LGI1 encephalitis, who were admitted in Beijing Tiantan Hospital between September 2014 and July 2019. The glucose metabolic pattern was compared between the included patients and 44 age- and gender-matched healthy controls using Statistical Parametric Mapping. Then, the correlation between the metabolic pattern and scaled activities of daily living (ADLs) of the patients was assessed.ResultsThe median time from symptom onset to PET scans was 9 w (range:2-53w). The groupwise analysis revealed that patients with anti-LGI1 encephalitis had left hippocampal hypermetabolism and hypometabolism in almost all neocortical regions. The individual-level results showed most patients presented a decreased metabolism in neocortical regions, as well as an increase in metabolism in the hippocampus and basal ganglia. Furthermore, the metabolic gradient between hippocampus and neocortical regions was positively associated with the ADLs (frontal lobe, r=0.529, P=0.008; parietal lobe, r=0.474, P=0.019; occipital lobe, r=0.413, P=0.045; temporal lobe, r=0.490, P=0.015), respectively. In addition, the patients with facio-brachial dystonic seizures (FBDS) presented bilateral putamen hypermetabolism, when compared to patients without FBDS and healthy controls.ConclusionSubcortical hypermetabolism associated with cortical hypometabolism presented with a common metabolic pattern in patients with anti-LGI1 encephalitis in the present study. The resolution of the metabolic gradient of the hippocampal hypermetabolism and neocortical hypometabolism may bring about improved clinical neurologic disability.

scholarly journals Repeatability of parametric methods for [18F]florbetapir imaging in Alzheimer’s disease and healthy controls: A test–retest study

2020 ◽  
pp. 0271678X2091540 ◽  
Author(s):  
Sander CJ Verfaillie ◽  
Sandeep SV Golla ◽  
Tessa Timmers ◽  
Hayel Tuncel ◽  
Chris WJ van der Weijden ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
Parametric Methods ◽  
Excellent Performance ◽  
Reference Tissue ◽  
Positron Emission ◽  
Arterial Sampling ◽  
Pet Scans

Accumulation of amyloid beta (Aβ) is one of the pathological hallmarks of Alzheimer’s disease (AD), which can be visualized using [18F]florbetapir positron emission tomography (PET). The aim of this study was to evaluate various parametric methods and to assess their test-retest (TRT) reliability. Two 90 min dynamic [18F]florbetapir PET scans, including arterial sampling, were acquired ( n = 8 AD patient, n = 8 controls). The following parametric methods were used; (reference:cerebellum); Logan and spectral analysis (SA), receptor parametric mapping (RPM), simplified reference tissue model2 (SRTM2), reference Logan (rLogan) and standardized uptake value ratios (SUVr(50–70)). BPND+1, DVR, VT and SUVr were compared with corresponding estimates (VT or DVR) from the plasma input reversible two tissue compartmental (2T4k_VB) model with corresponding TRT values for 90-scan duration. RPM ( r2 = 0.92; slope = 0.91), Logan ( r2 = 0.95; slope = 0.84) and rLogan ( r2 = 0.94; slope = 0.88), and SRTM2 ( r2 = 0.91; slope = 0.83), SA ( r2 = 0.91; slope = 0.88), SUVr ( r2 = 0.84; slope = 1.16) correlated well with their 2T4k_VB counterparts. RPM (controls: 1%, AD: 3%), rLogan (controls: 1%, AD: 3%) and SUVr(50–70) (controls: 3%, AD: 8%) showed an excellent TRT reliability. In conclusion, most parametric methods showed excellent performance for [18F]florbetapir, but RPM and rLogan seem the methods of choice, combining the highest accuracy and best TRT reliability.

scholarly journals Pathogenic PSEN1 Thr119Ile Mutation in Two Korean Patients with Early-Onset Alzheimer’s Disease

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 405
Author(s):  
Eva Bagyinszky ◽  
Hyon Lee ◽  
Jung Min Pyun ◽  
Jeewon Suh ◽  
Min Ju Kang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Early Onset ◽  
Emission Tomography ◽  
Korean Patients ◽  
Positron Emission ◽  
Mri Scans ◽  
Early Onset Alzheimer’S Disease

We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed diffuse atrophy in the fronto-parietal regions. In addition, 18F-fludeoxyglucose positron emission tomography (FDG-PET) showed reduced tracer uptake in the parietal and temporal cortices, bilaterally. The second patient developed memory dysfunction at the age of 49, and his mother was also affected. Amyloid positron emission tomography (PET) was positive, but MRI scans did not reveal any atrophy. Targeted NGS and Sanger sequencing identified a heterozygous C to T exchange in PSEN1 exon 5 (c.356C>T), resulting in a p.Thr119Ile mutation. The mutation is located in the conserved HL-I loop, where several Alzheimer’s disease (AD) related mutations have been described. Structure analyses suggested that Thr119Ile mutation may result in a significant change inside conservative loop. Additional in vitro studies are needed to estimate the role of the PSEN1 Thr119Ile in AD disease progression.

The Precuneus – A Witness for Excessive Aβ Gathering in Alzheimer’s Disease Pathology

2018 ◽  
Vol 18 (5-6) ◽  
pp. 302-309 ◽  
Author(s):  
Gayane Aghakhanyan ◽  
Andrea Vergallo ◽  
Marta Gennaro ◽  
Sara Mazzarri ◽  
Federica Guidoccio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Duration ◽  
Standardized Uptake Value ◽  
Positive Association ◽  
Analysis Of Covariance ◽  
Qualitative Assessment ◽  
Control Group ◽  
Positron Emission

Evidence of cortical beta-amyloid (Aβ) load, assessed by Aβ positron emission tomography (Aβ-PET), is an established in vivo biomarker of Alzheimer’s disease (AD)-related pathophysiology. Qualitative assessment of Aβ-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aβ burden along the continuum of AD. Methods: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aβ-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αβ distribution pattern considering age as a nuisance covariate. Results: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [18F]-flor­betapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. Conclusions: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aβ depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aβ. We found a positive association between the overall Aβ-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aβ deposition continuously takes place as the disease progresses.

Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer’s disease evaluated by β-amyloid positron emission tomography imaging

2020 ◽  
Vol 54 (9) ◽  
pp. 883-891
Author(s):  
Bok-Nam Park ◽  
Jang-Hee Kim ◽  
Tae Sung Lim ◽  
So Hyun Park ◽  
Tae-Gyu Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
Positron Emission ◽  
Β Amyloid

Objective: We evaluated the effects of bone marrow–derived mesenchymal stem cells in a model of Alzheimer’s disease using serial [18F]Florbetaben positron emission tomography. Methods: 3xTg Alzheimer’s disease mice were treated with intravenously injected bone marrow–derived mesenchymal stem cells, and animals without stem cell therapy were used as controls. Serial [18F]Florbetaben positron emission tomography was performed after therapy. The standardized uptake value ratio was measured as the cortex standardized uptake value divided by the cerebellum standardized uptake value. Memory function and histological changes were observed using the Barnes maze test and β-amyloid-reactive cells. Results: Standardized uptake value ratio decreased significantly from day 14 after stem cell administration in the bone marrow–derived mesenchymal stem cells–treated group ( n = 28). In contrast, there was no change in the ratio in control mice ( n = 25) at any time point. In addition, mice that received bone marrow–derived mesenchymal stem cell therapy also exhibited significantly better memory function and less β-amyloid-immunopositive plaques compared to controls. Conclusion: The therapeutic effect of intravenously injected bone marrow–derived mesenchymal stem cells in a mouse model of Alzheimer’s disease was confirmed by β-amyloid positron emission tomography imaging, memory functional studies and histopathological evaluation.

scholarly journals Development and evaluation of an automated quantification tool for amyloid PET images

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuma Tsubaki ◽  
◽  
Go Akamatsu ◽  
Natsumi Shimokawa ◽  
Suguru Katsube ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Studies ◽  
Parietal Lobe ◽  
Standardized Uptake Value ◽  
Posterior Cingulate Cortex ◽  
Amyloid Pet ◽  
Commercial Software ◽  
Anatomical Standardization ◽  
Automated Quantification

Abstract Background Quantitative evaluation of amyloid positron emission tomography (PET) with standardized uptake value ratio (SUVR) plays a key role in clinical studies of Alzheimer’s disease (AD). We have proposed a PET-only (MR-free) amyloid quantification method, although some commercial software packages are required. The aim of this study was to develop an automated quantification tool for amyloid PET without using commercial software. Methods The quantification tool was created by combining four components: (1) anatomical standardization to positive and negative templates using NEUROSTAT stereo.exe; (2) similarity calculation between standardized images and respective templates based on normalized cross-correlation (selection of the image for SUVR measurement); (3) voxel value normalization by the mean value of reference regions (making an SUVR-scaled image); and (4) SUVR calculation based on pre-defined regions of interest (ROIs). We examined 166 subjects who underwent a [11C] Pittsburgh compound-B PET scan through the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI) study. SUVRs in five ROIs (frontal lobe, temporal lobe, parietal lobe, occipital lobe, and posterior cingulate cortex and precuneus) were calculated with the cerebellar cortex as the reference region. The SUVRs obtained by our tool were compared with manual step-by-step processing and the conventional PMOD-based method (PMOD Technologies, Switzerland). Results Compared with manual step-by-step processing, our developed automated quantification tool reduced processing time by 85%. The SUVRs obtained by the developed quantification tool were consistent with those obtained by manual processing. Compared with the conventional PMOD-based method, the developed quantification tool provided 1.5% lower SUVR values, on average. We determined that this bias is likely due to the difference in anatomical standardization methods. Conclusions We developed an automated quantification tool for amyloid PET images. Using this tool, SUVR values can be quickly measured without individual MRI and without commercial software. This quantification tool may be useful for clinical studies of AD.

scholarly journals Comparison of subtyping methods for neuroimaging studies in Alzheimer’s disease: a call for harmonization

2020 ◽  
Author(s):  
Rosaleena Mohanty ◽  
Gustav Mårtensson ◽  
Konstantinos Poulakis ◽  
J-Sebastian Muehlboeck ◽  
Elena Rodriguez-Vieitez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Reference Group ◽  
Group Level ◽  
Healthy Individuals ◽  
Individual Level ◽  
Dementia Patients ◽  
Tau Pet ◽  
The Individual

Abstract Biological subtypes in Alzheimer’s disease, originally identified on neuropathological data, have been translated to in vivo biomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within Alzheimer’s disease. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context. We compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive Alzheimer’s disease dementia patients (reference group: 70 amyloid-beta negative healthy individuals) using sMRI. Secondly, we extended and applied the subtyping methods to 53 amyloid-beta positive prodromal Alzheimer’s disease and 30 amyloid-beta positive Alzheimer’s disease dementia patients (reference group: 200 amyloid-beta negative healthy individuals) using sMRI and tau PET. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed. Each individual subtyping method was replicated, and the proof-of-concept was established. At the group level, all methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar cortical thinning and tau PET uptake patterns. However, at the individual level large disagreements were found in subtype assignments. Although characteristics of subtypes are comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for establishment of an open benchmarking framework to overcome this problem.

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