scholarly journals Case Report: 18F-MK6240 Tau Positron Emission Tomography Pattern Resembling Chronic Traumatic Encephalopathy in a Retired Australian Rules Football Player

2020 ◽  
Vol 11 ◽  
Author(s):  
Natasha Krishnadas ◽  
Vincent Doré ◽  
Fiona Lamb ◽  
Colin Groot ◽  
Paul McCrory ◽  
...  
Keyword(s):  
Short Term Memory ◽  
Small Vessel Disease ◽  
Chronic Traumatic Encephalopathy ◽  
Amyloid Β ◽  
Football Player ◽  
Cognitively Impaired ◽  
Positron Emission ◽  
Prodromal Ad ◽  
Australian Rules Football ◽  
Prodromal Alzheimer’S Disease

Introduction: It remains unclear if tau imaging may assist diagnosis of chronic traumatic encephalopathy (CTE). Flortaucipir PET has shown superior frontal with medial temporal tau binding consistent with the provisional neuropathological criteria for mid-stage CTE in group-level analyses of retired symptomatic NFL players and in one individual with pathologically confirmed CTE. 18F-MK6240 is a new PET ligand that has high affinity for tau. We present the case of a 63-year-old cognitively impaired, former Australian rules football player with distinct superior frontal and medial temporal 18F-MK6240 binding and show it to be significantly different to the pattern seen in prodromal Alzheimer's disease (AD).Findings: The participant was recruited for a study of amyloid-β and tau several decades after traumatic brain injury. He had multiple concussions during his football career but no cognitive complaints at retirement. A thalamic stroke in his mid 50s left stable mild cognitive deficits but family members reported further short-term memory, behavioral, and personality decline preceding the study. Imaging showed extensive small vessel disease on MRI, a moderate burden of amyloid-β plaques, and 18F-MK6240 binding in bilateral superior frontal and medial temporal cortices. Voxel-wise analysis demonstrated that the frontally predominant pattern of the participant was significantly different to the posterior temporo-parietal predominant pattern of prodromal AD.Conclusion: Although lacking neuropathological examination to distinguish CTE from a variant of AD, the clear demonstration of a CTE-like tau pattern in a single at-risk individual suggests further research on the potential of 18F-MK6240 PET for identifying CTE is warranted.

scholarly journals Tau Positron Emission Tomographic Findings in a Former US Football Player With Pathologically Confirmed Chronic Traumatic Encephalopathy

2020 ◽  
Vol 77 (4) ◽  
pp. 517 ◽  
Author(s):  
William G. Mantyh ◽  
Salvatore Spina ◽  
Alex Lee ◽  
Leonardo Iaccarino ◽  
David Soleimani-Meigooni ◽  
...  
Keyword(s):  
Chronic Traumatic Encephalopathy ◽  
Football Player ◽  
Positron Emission Tomographic ◽  
Positron Emission

scholarly journals Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3600-3607 ◽  
Author(s):  
Young Hee Jung ◽  
Hyemin Jang ◽  
Seong Beom Park ◽  
Yeong Sim Choe ◽  
Yuhyun Park ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Disease Burden ◽  
Dentate Nucleus ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Cerebral Microbleeds ◽  
Amyloid Angiopathy ◽  
Positron Emission ◽  
Aβ Amyloid ◽  
Cerebral Amyloid

Background and Purpose: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. Methods: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. Results: The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P <0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P =0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P =0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%, P =0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P =0.041) than the dentate group. Conclusions: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

Insomnia Moderates the Relationship Between Amyloid-β and Cognitive Decline in Late-Life Adults without Dementia

2021 ◽  
pp. 1-10
Author(s):  
Wei Xu ◽  
Chen-Chen Tan ◽  
Juan-Juan Zou ◽  
Xi-Peng Cao ◽  
Lan Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Amyloid Β ◽  
Cognitive Disorders ◽  
Linear Mixed Effects ◽  
Positron Emission ◽  
Prodromal Ad ◽  
Neuropsychological Evaluations ◽  
The Relationship

Background: It is suggested that not all individuals with elevated Aβ will develop dementia or cognitive impairment. Environment or lifestyle might modulate the association of amyloid pathology with cognition. Insomnia is a risk factor of cognitive disorders including Alzheimer’s disease. Objective: To investigate if insomnia moderated the relationship between amyloid-β (Aβ) and longitudinal cognitive performance in non-demented elders. Methods: A total of 385 Alzheimer’s Disease Neuroimaging Initiative participants (mean age = 73 years, 48% females) who completed 4 + neuropsychological evaluations and a [18F] florbetapir positron emission tomography scan were followed up to 8 years. Linear mixed-effects regression models were used to examine the interactions effect between insomnia and Aβ on longitudinal cognitive sores, including four domains (memory [MEM], executive function [EF], language [LAN], and visuospatial function [VS]). Results: The Aβ-positive status (A+) but not insomnia independently predicted faster cognitive decline in all domains. Furthermore, the relationship between Aβ and cognitive decline was moderated by insomnia (MEM: χ 2 = 4.05, p = 0.044, EF: χ 2 = 4.38, p = 0.036, LAN: χ 2 = 4.56, p = 0.033, and VS: χ 2 = 4.12, p = 0.042). Individuals with both elevated Aβ and insomnia experienced faster cognitive decline than those with only elevated Aβ or insomnia. Conclusion: These data reinforced the values of insomnia management in preventing dementia, possibly by interacting Aβ metabolism. Future efforts are warranted to determine whether sleep improvement will postpone the onset of dementia, specifically among populations in stages of preclinical or prodromal AD.

scholarly journals Longitudinal pathways of cerebrospinal fluid and positron emission tomography biomarkers of amyloid-β positivity

2020 ◽  
Author(s):  
Arianna Sala ◽  
◽  
Agneta Nordberg ◽  
Elena Rodriguez-Vieitez
Keyword(s):  
Amyloid Β ◽  
Clinical Information ◽  
Alternative Pathways ◽  
Positron Emission ◽  
Risk Of Progression ◽  
Prodromal Alzheimer’S Disease ◽  
History Of ◽  
Genetic Profiles ◽  
Pet Amyloid

AbstractMismatch between CSF and PET amyloid-β biomarkers occurs in up to ≈20% of preclinical/prodromal Alzheimer’s disease individuals. Factors underlying mismatching results remain unclear. In this study we hypothesized that CSF/PET discordance provides unique biological/clinical information. To test this hypothesis, we investigated non-demented and demented participants with CSF amyloid-β42 and [18F]Florbetapir PET assessments at baseline (n = 867) and at 2-year follow-up (n = 289). Longitudinal trajectories of amyloid-β positivity were tracked simultaneously for CSF and PET biomarkers. In the longitudinal cohort (n = 289), we found that participants with normal CSF/PET amyloid-β biomarkers progressed more frequently toward CSF/PET discordance than to full CSF/PET positivity (χ2(1) = 5.40; p < 0.05). Progression to CSF+/PET+ status was ten times more frequent in cases with discordant biomarkers, as compared to csf−/pet− cases (χ2(1) = 18.86; p < 0.001). Compared to the CSF+/pet− group, the csf−/PET+ group had lower APOE-ε4ε4 prevalence (χ2(6) = 197; p < 0.001; n = 867) and slower rate of brain amyloid-β accumulation (F(3,600) = 12.76; p < 0.001; n = 608). These results demonstrate that biomarker discordance is a typical stage in the natural history of amyloid-β accumulation, with CSF or PET becoming abnormal first and not concurrently. Therefore, biomarker discordance allows for identification of individuals with elevated risk of progression toward fully abnormal amyloid-β biomarkers, with subsequent risk of neurodegeneration and cognitive decline. Our results also suggest that there are two alternative pathways (“CSF-first” vs. “PET-first”) toward established amyloid-β pathology, characterized by different genetic profiles and rates of amyloid-β accumulation. In conclusion, CSF and PET amyloid-β biomarkers provide distinct information, with potential implications for their use as biomarkers in clinical trials.

scholarly journals Accurate Transmission-Less Attenuation Correction Method for Amyloid-β Brain PET Using Deep Neural Network

Electronics ◽  
2021 ◽  
Vol 10 (15) ◽  
pp. 1836
Author(s):  
Bo-Hye Choi ◽  
Donghwi Hwang ◽  
Seung-Kwan Kang ◽  
Kyeong-Yun Kim ◽  
Hongyoon Choi ◽  
...  
Keyword(s):  
Neural Network ◽  
Attenuation Correction ◽  
Complex Structure ◽  
Scatter Correction ◽  
Amyloid Β ◽  
Correction Method ◽  
Percentage Error ◽  
Similarity Coefficients ◽  
Brain Pet ◽  
Positron Emission

The lack of physically measured attenuation maps (μ-maps) for attenuation and scatter correction is an important technical challenge in brain-dedicated stand-alone positron emission tomography (PET) scanners. The accuracy of the calculated attenuation correction is limited by the nonuniformity of tissue composition due to pathologic conditions and the complex structure of facial bones. The aim of this study is to develop an accurate transmission-less attenuation correction method for amyloid-β (Aβ) brain PET studies. We investigated the validity of a deep convolutional neural network trained to produce a CT-derived μ-map (μ-CT) from simultaneously reconstructed activity and attenuation maps using the MLAA (maximum likelihood reconstruction of activity and attenuation) algorithm for Aβ brain PET. The performance of three different structures of U-net models (2D, 2.5D, and 3D) were compared. The U-net models generated less noisy and more uniform μ-maps than MLAA μ-maps. Among the three different U-net models, the patch-based 3D U-net model reduced noise and cross-talk artifacts more effectively. The Dice similarity coefficients between the μ-map generated using 3D U-net and μ-CT in bone and air segments were 0.83 and 0.67. All three U-net models showed better voxel-wise correlation of the μ-maps compared to MLAA. The patch-based 3D U-net model was the best. While the uptake value of MLAA yielded a high percentage error of 20% or more, the uptake value of 3D U-nets yielded the lowest percentage error within 5%. The proposed deep learning approach that requires no transmission data, anatomic image, or atlas/template for PET attenuation correction remarkably enhanced the quantitative accuracy of the simultaneously estimated MLAA μ-maps from Aβ brain PET.

scholarly journals Case of early-onset Alzheimer’s disease with atypical manifestation

2021 ◽  
Vol 34 (1) ◽  
pp. e100283
Author(s):  
Lin Zhu ◽  
Limin Sun ◽  
Lin Sun ◽  
Shifu Xiao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Manifestation ◽  
Early Onset ◽  
Short Term Memory ◽  
Brain Mri ◽  
Memory Loss ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Fluent Aphasia

Short-term memory decline is the typical clinical manifestation of Alzheimer’s disease (AD). However, early-onset AD usually has atypical symptoms and may get misdiagnosed. In the present case study, we reported a patient who experienced symptoms of memory loss with progressive non-fluent aphasia accompanied by gradual social withdrawal. He did not meet the diagnostic criteria of AD based on the clinical manifestation and brain MRI. However, his cerebrospinal fluid examination showed a decreased level of beta-amyloid 42, and increased total tau and phosphorylated tau. Massive amyloid β-protein deposition by 11C-Pittsburgh positron emission tomography confirmed the diagnosis of frontal variant AD. This case indicated that early-onset AD may have progressive non-fluent aphasia as the core manifestation. The combination of individual and precision diagnosis would be beneficial for similar cases.

scholarly journals Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer’s Disease and Other Dementias

2020 ◽  
pp. 1-14
Author(s):  
Yi-Wen Bao ◽  
Anson C.M. Chau ◽  
Patrick Ka-Chun Chiu ◽  
Yat Fung Shea ◽  
Joseph S.K. Kwan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Subjective Cognitive Decline ◽  
Cognitively Impaired ◽  
Memory Clinic ◽  
Pet Ct

Background: With the more widespread use of 18F-radioligand-based amyloid-β (Aβ) PET-CT imaging, we evaluated Aβ binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. Objective: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer’s disease (AD), and 2) MCI from other non-AD dementias (OD). Methods: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). Results: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aβ binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. Conclusion: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.

scholarly journals Cerebral amyloid angiopathy severity is linked to dilation of juxtacortical perivascular spaces

2015 ◽  
Vol 36 (3) ◽  
pp. 576-580 ◽  
Author(s):  
Susanne J van Veluw ◽  
Geert Jan Biessels ◽  
Willem H Bouvy ◽  
Wim GM Spliet ◽  
Jaco JM Zwanenburg ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Resonance Imaging ◽  
Centrum Semiovale ◽  
Tissue Sections ◽  
Cortical Areas ◽  
Cerebral Amyloid

Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3–7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity.

Cognitive and Physiological Substrates of Impaired Sentence Processing in Parkinson's Disease

1993 ◽  
Vol 5 (4) ◽  
pp. 480-498 ◽  
Author(s):  
Murray Grossman ◽  
Susan Carvell ◽  
Stephen Gollomp ◽  
Matthew B. Stern ◽  
Martin Reivich ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Frontal Cortex ◽  
Sentence Processing ◽  
Sentence Comprehension ◽  
Short Term Memory ◽  
Brain Regions ◽  
Positron Emission ◽  
Left Caudate ◽  
Regional Cerebral Glucose Metabolism

Sentence comprehension is a complex process involving at least a grammatical processor and a procedural component that supports language computations. One type of cerebral architecture that may underlie sentence processing is a network of distributed brain regions. We report two experiments designed to evaluate the cognitive and physiological substrate of sentence processing diaculties in nondemented patients with Parkinson's disease (PD). In the first experiment, patients answered simple questions about sentences that varied in their computational demands. Group and individual patient analyses indicated that PD patients are significantly compromised on this task, and that their difficulties become more prominent as the computational demands of the sentences increase. We manipulated the set of sentences to stress performance aspects of sentence processing. PD patients were compromised in their ability to detect errors in the presence and nature of a sentence's grammatical morphemes, suggesting a deficit in selective attention, but their ability to answer questions about a sentence was not afFected by short-term memory factors. In the second experiment, positron emission tomography was used to correlate this pattern of sentence comprehension impairment with regional cerebral glucose metabolism (rCMRgl) obtained at rest in a representative subset of these PD patients. Grammatical comprehension and attention in sentence processing correlated significantly with mesial frontal rCMRgl. Regression analyses confirmed the central role of left mesial frontal cortex, and identified a subsidiary role for left caudate in overall sentence comprehension, for left dorsolateral frontal cortex in grammatical processing, and for bilateral dorsolateral frontal cortex in attending to the presence of grammatical features. We conclude that compromised mesial frontal functioning underlies in part the sentence processing deficit of these patients, and these data illustrate one method for mapping portions of a sentence processing mechanism onto a distributed cerebral architecture.

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