scholarly journals Dynamic planar scintigraphy for the rapid kinetic measurement of myocardial 123I-MIBG turnover can identify Lewy body disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshitaka Kumakura ◽  
Yuji Shimizu ◽  
Masatsugu Hariu ◽  
Ken-ichi Ichikawa ◽  
Norihito Yoshida ◽  
...  
Keyword(s):  
Lewy Body ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Myocardial Scintigraphy ◽  
Turnover Rates ◽  
Planar Imaging ◽  
Time Activity ◽  
Model Based ◽  
Potential Association ◽  
Fractional Distribution

Abstract Background Using two static scans for 123I-meta-iodobenzyl-guanidine (123I-MIBG) myocardial scintigraphy ignores the dynamic response from vesicular trapping in nerve terminals. Moreover, the long pause between scans is impractical for patients with Lewy body diseases (LBDs). Here, we optimized indices that capture norepinephrine kinetics, tested their diagnostic performance, and determined the differences in 123I-MIBG performance among disease groups. Methods We developed a new 30-min protocol for 123I-MIBG dynamic planar imaging for suspected LBD patients. Pharmacokinetic modelling of time-activity curves (TACs) was used to calculate three new indices: unidirectional uptake of 123I-MIBG to vesicular trapping (iUp), rate of myocardial 123I-MIBG loss (iLoss), and non-specific fractional distribution of 123I-MIBG in the interstitial space. We compared the performance of the new and existing indices with regard to discrimination of patients with or without LBDs. Subgroup analysis was performed to examine differences in 123I-MIBG turnover between patients in a dementia with Lewy bodies (DLB) group and two Parkinson’s disease (PD) groups, one with and the other without REM sleep behaviour disorder (RBD). Results iLoss was highly discriminative, particularly for patients with low myocardial 123I-MIBG trapping, and the new indices outperformed existing ones. ROC analysis revealed that the AUC of iLoss (0.903) was significantly higher than that of early HMR (0.863), while comparable to that of delayed HMR (0.892). The RBD-positive PD group and the DLB group had higher turnover rates than the RBD-negative PD group, indicating a potential association between prognosis and iLoss. Conclusion 123I-MIBG turnover can be quantified in 30 min using a three-parameter model based on 123I-MIBG TACs. The discriminatory performance of the new model-based indices might help explain the neurotoxicity or neurodegeneration that occurs in LBD patients.

Clinical Aspects of Non-Alzheimer Disease Dementias

2017 ◽  
Author(s):  
David Knopman
Keyword(s):  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cerebrovascular Disease ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Clinical Aspects ◽  
Key Words Dementia ◽  
Sleep Behavior

There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN, and C9ORF72). Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment

scholarly journals Diagnostic accuracy of dopaminergic imaging in prodromal dementia with Lewy bodies

2018 ◽  
Vol 49 (3) ◽  
pp. 396-402 ◽  
Author(s):  
Alan J. Thomas ◽  
Paul Donaghy ◽  
Gemma Roberts ◽  
Sean J. Colloby ◽  
Nicky A. Barnett ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
High Specificity ◽  
Diagnostic Confidence ◽  
Neuropsychological Assessments ◽  
Diagnostic Symptoms ◽  
Prodromal Dementia

AbstractBackgroundDopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.MethodsWe recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.ResultsThe sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).ConclusionsDopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.

scholarly journals 18F-fluorodeoxyglucose positron emission tomography in dementia with Lewy bodies

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Jonathan Graff-Radford ◽  
Timothy G Lesnick ◽  
Rodolfo Savica ◽  
Qin Chen ◽  
Tanis J Ferman ◽  
...  
Keyword(s):  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Rating Scale ◽  
Clinical Course ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Diffuse Lewy Body Disease ◽  
18F Fluorodeoxyglucose ◽  
Alzheimer’S Pathology ◽  
Fluorodeoxyglucose Pet

Abstract Among individuals with dementia with Lewy bodies, pathologic correlates of clinical course include the presence and extent of coexisting Alzheimer’s pathology and the presence of transitional or diffuse Lewy body disease. The objectives of this study are to determine (i) whether 18F-fluorodeoxyglucose PET signature patterns of dementia with Lewy bodies are associated with the extent of coexisting Alzheimer’s pathology and the presence of transitional or diffuse Lewy body disease and (ii) whether these 18F-fluorodeoxyglucose pattern(s) are associated with clinical course in dementia with Lewy bodies. Two groups of participants were included: a pathology-confirmed subset with Lewy body disease (n = 34) and a clinically diagnosed group of dementia with Lewy bodies (n = 87). A subset of the clinically diagnosed group was followed longitudinally (n = 51). We evaluated whether 18F-fluorodeoxyglucose PET features of dementia with Lewy bodies (higher cingulate island sign ratio and greater occipital hypometabolism) varied by Lewy body disease subtype (transitional versus diffuse) and Braak neurofibrillary tangle stage. We investigated whether the PET features were associated with the clinical trajectories by performing regression models predicting Clinical Dementia Rating Scale Sum of Boxes. Among autopsied participants, there was no difference in cingulate island sign or occipital hypometabolism by Lewy body disease type, but those with a lower Braak tangle stage had a higher cingulate island sign ratio compared to those with a higher Braak tangle stage. Among the clinically diagnosed dementia with Lewy bodies participants, a higher cingulate island ratio was associated with better cognitive scores at baseline and longitudinally. A higher 18F-fluorodeoxyglucose PET cingulate island sign ratio was associated with lower Braak tangle stage at autopsy, predicted a better clinical trajectory in dementia with Lewy body patients and may allow for improved prognostication of the clinical course in this disease.

scholarly journals Lewy pathology of the esophagus correlates with the progression of Lewy body disease: a Japanese cohort study of autopsy cases

2020 ◽  
Vol 141 (1) ◽  
pp. 25-37
Author(s):  
Zen-ichi Tanei ◽  
Yuko Saito ◽  
Shinji Ito ◽  
Tomoyasu Matsubara ◽  
Atsuko Motoda ◽  
...  
Keyword(s):  
Nervous System ◽  
Lewy Body ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Wide Distribution ◽  
Esophageal Wall ◽  
Motor Symptoms ◽  
Aging Research ◽  
Lewy Pathology ◽  
Japanese Cohort

AbstractLewy body disease (LBD) is a spectrum of progressive neurodegenerative disorders characterized by the wide distribution of Lewy bodies and neurites in the central and peripheral nervous system (CNS, PNS). Clinical diagnoses include Parkinson’s disease (PD), dementia with Lewy bodies, or pure autonomic failure. All types of LBD are accompanied by non-motor symptoms (NMSs) including gastrointestinal dysfunctions such as constipation. Its relationship to Lewy body-related α-synucleinopathy (Lewy pathology) of the enteric nervous system (ENS) is attracting attention because it can precede the motor symptoms. To clarify the role of ENS Lewy pathology in disease progression, we performed a clinicopathological study using the Brain Bank for Aging Research in Japan. Five-hundred and eighteen cases were enrolled in the study. Lewy pathology of the CNS and PNS, including the lower esophagus as a representative of the ENS, was examined via autopsy findings. Results showed that one-third of older people (178 cases, 34%) exhibited Lewy pathology, of which 78 cases (43.8%) exhibited the pathology in the esophagus. In the esophageal wall, Auerbach’s plexus (41.6%) was most susceptible to the pathology, followed by the adventitia (33.1%) and Meissner’s plexus (14.6%). Lewy pathology of the esophagus was significantly associated with autonomic failures such as constipation (p < 0.0001) and among PNS regions, correlated the most with LBD progression (r = 0.95, p < 0.05). These findings suggest that the propagation of esophageal Lewy pathology is a predictive factor of LBD.

scholarly journals Deubiquitinase Usp8 regulates α-synuclein clearance and modifies its toxicity in Lewy body disease

2016 ◽  
Vol 113 (32) ◽  
pp. E4688-E4697 ◽  
Author(s):  
Zoi Alexopoulou ◽  
Johannes Lang ◽  
Rebecca M. Perrett ◽  
Myriam Elschami ◽  
Madeleine E. D. Hurry ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Lewy Body ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Cell Loss ◽  
Lysosomal Degradation ◽  
Endosomal Membranes ◽  
Locomotor Deficits ◽  
Outstanding Question ◽  
In Cells

In Parkinson’s disease, misfolded α-synuclein accumulates, often in a ubiquitinated form, in neuronal inclusions termed Lewy bodies. An important outstanding question is whether ubiquitination in Lewy bodies is directly relevant to α-synuclein trafficking or turnover and Parkinson’s pathogenesis. By comparative analysis in human postmortem brains, we found that ubiquitin immunoreactivity in Lewy bodies is largely due to K63-linked ubiquitin chains and markedly reduced in the substantia nigra compared with the neocortex. The ubiquitin staining in cells with Lewy bodies inversely correlated with the content and pathological localization of the deubiquitinase Usp8. Usp8 interacted and partly colocalized with α-synuclein in endosomal membranes and, both in cells and after purification, it deubiquitinated K63-linked chains on α-synuclein. Knockdown of Usp8 in the Drosophila eye reduced α-synuclein levels and α-synuclein–induced eye toxicity. Accordingly, in human cells, Usp8 knockdown increased the lysosomal degradation of α-synuclein. In the dopaminergic neurons of the Drosophila model, unlike knockdown of other deubiquitinases, Usp8 protected from α-synuclein–induced locomotor deficits and cell loss. These findings strongly suggest that removal of K63-linked ubiquitin chains on α-synuclein by Usp8 is a critical mechanism that reduces its lysosomal degradation in dopaminergic neurons and may contribute to α-synuclein accumulation in Lewy body disease.

A pathological study of Lewy bodies and senile changes in the amygdala in diffuse Lewy body disease

1995 ◽  
Vol 15 (3-4) ◽  
pp. 112-116 ◽  
Author(s):  
Eizo Iseki ◽  
Toshinari Odawara ◽  
Kyoko Suzuki ◽  
Kenji Kosaka ◽  
Haruhiko Akiyama ◽  
...  
Keyword(s):  
Lewy Body ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Pathological Study ◽  
Diffuse Lewy Body Disease ◽  
Senile Changes

The Role of 123I-Metaiodobenzylguanidine Myocardial Scintigraphy in the Diagnosis of Lewy Body Disease in Patients with Dementia in a Memory Clinic

2006 ◽  
Vol 22 (5-6) ◽  
pp. 379-384 ◽  
Author(s):  
Haruo Hanyu ◽  
Soichiro Shimizu ◽  
Kentaro Hirao ◽  
Hirofumi Sakurai ◽  
Toshihiko Iwamoto ◽  
...  
Keyword(s):  
Lewy Body ◽  
Lewy Body Disease ◽  
Myocardial Scintigraphy ◽  
Memory Clinic

scholarly journals It Is Time to Study Overlapping Molecular and Circuit Pathophysiologies in Alzheimer’s and Lewy Body Disease Spectra

2021 ◽  
Vol 15 ◽  
Author(s):  
Noritaka Wakasugi ◽  
Takashi Hanakawa
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Continuous Spectrum ◽  
Lewy Body ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Lewy Body Disease ◽  
Common Mechanism ◽  
Protein Accumulation ◽  
The Brain

Alzheimer’s disease (AD) is the leading cause of dementia due to neurodegeneration and is characterized by extracellular senile plaques composed of amyloid β1–42 (Aβ) as well as intracellular neurofibrillary tangles consisting of phosphorylated tau (p-tau). Dementia with Lewy bodies constitutes a continuous spectrum with Parkinson’s disease, collectively termed Lewy body disease (LBD). LBD is characterized by intracellular Lewy bodies containing α-synuclein (α-syn). The core clinical features of AD and LBD spectra are distinct, but the two spectra share common cognitive and behavioral symptoms. The accumulation of pathological proteins, which acquire pathogenicity through conformational changes, has long been investigated on a protein-by-protein basis. However, recent evidence suggests that interactions among these molecules may be critical to pathogenesis. For example, Aβ/tau promotes α-syn pathology, and α-syn modulates p-tau pathology. Furthermore, clinical evidence suggests that these interactions may explain the overlapping pathology between AD and LBD in molecular imaging and post-mortem studies. Additionally, a recent hypothesis points to a common mechanism of prion-like progression of these pathological proteins, via neural circuits, in both AD and LBD. This suggests a need for understanding connectomics and their alterations in AD and LBD from both pathological and functional perspectives. In AD, reduced connectivity in the default mode network is considered a hallmark of the disease. In LBD, previous studies have emphasized abnormalities in the basal ganglia and sensorimotor networks; however, these account for movement disorders only. Knowledge about network abnormalities common to AD and LBD is scarce because few previous neuroimaging studies investigated AD and LBD as a comprehensive cohort. In this paper, we review research on the distribution and interactions of pathological proteins in the brain in AD and LBD, after briefly summarizing their clinical and neuropsychological manifestations. We also describe the brain functional and connectivity changes following abnormal protein accumulation in AD and LBD. Finally, we argue for the necessity of neuroimaging studies that examine AD and LBD cases as a continuous spectrum especially from the proteinopathy and neurocircuitopathy viewpoints. The findings from such a unified AD and Parkinson’s disease (PD) cohort study should provide a new comprehensive perspective and key data for guiding disease modification therapies targeting the pathological proteins in AD and LBD.

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