Striatal monoamine terminals in Lewy body dementia and Alzheimer's disease

Gilman, Sid; Koeppe, Robert A.; Little, Roderick J. A.; An, Hyonggin; Junck, Larry; Giordani, Bruno; Persad, Carol; Heumann, Mary; Wernette, Kris

doi:10.1002/ana.20088

Cited by 59 publications

(35 citation statements)

References 38 publications

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“…The greatest VMAT2 reductions were observed in the posterior putamen (281%), followed by the anterior putamen (270%), and caudate nucleus (248%). These results are consistent with previous 11 C-DTBZ PET results showing the highest reduction (71%277%) in the posterior putamen of PD patients (8,9,19,20). Our observations are also consistent with postmortem reports showing 88% reduction of VMAT2 immunoreactivity in the putamen of PD patients (21).…”

Section: Discussionsupporting

confidence: 93%

“…A longitudinal study in mildly affected PD patients or individuals at risk of PD will elucidate the usefulness of this tracer for early or presymptomatic diagnosis of PD (6). As shown in previous PET and SPECT studies (19,22,23), the evaluation of presynaptic dopaminergic integrity would also be useful in the differential diagnosis of dementia with Lewy bodies (DLB) from Alzheimer disease (AD), for which severe nigrostriatal dopaminergic degeneration, similar to that observed in PD, is present in DLB but not in AD. Additional studies comparing 18 F-AV-133 binding in DLB and AD patients are warranted.…”

Section: Discussionmentioning

confidence: 83%

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In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with ¹⁸F-AV-133

Okamura¹,

Villemagne²,

Drago³

et al. 2010

J Nucl Med

130

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PET provides a noninvasive means to evaluate the functional integrity of the presynaptic monoaminergic system in the living human brain. Methods: In this study, a novel 18 F-labeled tetrabenazine derivative, 18 F-(1)fluoropropyldihydrotetrabenazine ( 18 F-AV-133), was used for the noninvasive assessment of the vesicular monoamine transporters type 2 (VMAT2) in 17 Parkinson disease (PD) patients and 6 healthy controls. The binding potential (BP) of 18 F-AV-133 was calculated using Logan graphical analysis. Voxel-based and volume-of-interest-based analyses of BP images were performed to examine brain regional reductions in VMAT2 density in PD. Results: VMAT2 BP was decreased by 81% in the posterior putamen, 70% in the anterior putamen, and 48% in the caudate nucleus of PD patients. Voxelbased analysis demonstrated VMAT2 reductions in the striatum and mid brain of PD patients. Furthermore, VMAT2 BPs in the caudate nuclei significantly correlated with the clinical severity of PD. Conclusion: These findings indicate that the novel 18 Flabeled ligand 18 F-AV-133 can sensitively detect monoaminergic terminal reductions in PD patients. Studies with 18 F-AV-133 may allow the presymptomatic identification of individuals with disorders characterized by degeneration of dopaminergic nigrostriatal afferents.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 83%

In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with ¹⁸F-AV-133

Okamura¹,

Villemagne²,

Drago³

et al. 2010

J Nucl Med

130

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“…This pathologic feature can be studied via neuroimaging using radioligand binding to the DAT or vesicular monoamine transporter (22)(23)(24)(25). SPECT with 123 I-b-carbomethoxy-3ß-(4-iodophenyl)tropane ( 123 I-b-CIT) examining the ratio of binding in the striatum to binding in the occipital cortex has been shown to reliably quantify DAT density (26).…”

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confidence: 99%

The ¹⁸F-FDG PET Cingulate Island Sign and Comparison to ¹²³I-β-CIT SPECT for Diagnosis of Dementia with Lewy Bodies

Lim¹,

Katsifis²,

Villemagne³

et al. 2009

J Nucl Med

266

189

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Neuroimaging is increasingly used to supplement the clinical diagnosis of dementia with Lewy bodies (DLB) by showing reduced occipital metabolism and perfusion and reduced striatal dopaminergic innervation. We aimed to optimize the interpretation of 18 F-FDG PET images for differentiating DLB from Alzheimer disease (AD) and to compare the results with dopamine transporter imaging using 123 I-b-carbomethoxy-3ß-(4-iodophenyl)-tropane ( 123 I-b-CIT) SPECT. Methods: Fourteen subjects with a clinical diagnosis of DLB and 10 with AD underwent both 18 F-FDG PET and 123 I-b-CIT SPECT. Four DLB and 1 AD diagnoses were subsequently confirmed at autopsy. Diagnostic accuracy was calculated for visual interpretation by 3 readers of standard 3-plane and stereotactic surface projection 18 F-FDG PET images, receiver-operating-characteristic analysis of regional 18 F-FDG uptake, and a cutoff value for the striatal-to-occipital binding ratio of b-CIT defined by receiver-operating-characteristic analysis. Results: Visual interpretation of 3-plane 18 F-FDG PET images had a sensitivity of 83% and specificity of 93% for DLB, slightly higher than the results with the stereotactic surface projection images. Regionally, hypometabolism in the lateral occipital cortex had the highest sensitivity (88%), but relative preservation of the mid or posterior cingulate gyrus (cingulate island sign) had the highest specificity (100%). Region-of-interest analysis revealed that occipital hypometabolism and relative preservation of the posterior cingulate both had a sensitivity of 77% and specificity of 80%. b-CIT achieved 100% accuracy and greater effect size than did 18 F-FDG PET (Cohen d 5 4.1 vs. 1.9). Conclusion: Both 18 F-FDG PET and 123 I-b-CIT SPECT appear useful for the diagnosis of DLB, although the latter provides more robust results. The cingulate island sign may enhance the specificity of 18 F-FDG PET.

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“…Either PET or SPECT can be employed to provide functional imaging of the nigrostriatal dopaminergic system in vivo. SPECT has the advantage of being more readily available and somewhat easier to organize and undertake, and the majority of the reported studies of imaging of the dopaminergic system in DLB have been SPECT studies, even though PET has produced equivalent results [91]. The first ligand used in SPECT was [123I]-2b-carbomethoxy-3b-(4-iodophenyl) tropane (b-CIT).…”

Section: Other Investigations and Future Prospectivesmentioning

confidence: 99%

Is There a Place for Clinical Neurophysiology Assessments in Synucleinopathies?

Onofrj¹,

Bonanni²,

Thomas³

et al. 2011

Neuroimaging for Clinicians - Combining Research and Practice

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IntroductionParkinson Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) are characterized by deposition of Lewy Bodies (LB), consisting of eosinophilic intracellular (intraneural in PD and DLB and intraglial in MSA) inclusions of -synuclein and allowing the three disorders to be categorized as synucleinopathies. The identification in the last two decades of specific clinical features of synucleinopathies has been a major breakthrough in Neurology, as it prompted a reconsideration of diagnostic and therapeutic approaches to dementia and parkinsonism. The recognition of synuclein and ubiquitin markers in dementia resulted in the reclassification of patients previously considered as affected by Alzheimer Disease (AD) and Vascular Dementia (VaD), and there is now agreement that DLB is the second most common cause of dementia in elderly population: its prevalence is reported to be in the 25-43% range in different studies. DLB is clinically characterized by the presence of prominently dysexecutive dementia (frontal lobe or subcortical dementia according to earlier classification [1]), cognitive fluctuations, consisting of remitting-relapsing episodes of blunted conscience reaching levels of stupor, by the occurrence of visual hallucinations and delusions, by parkinsonian motor signs and hypersensitivity to neuroleptic treatment, ranging from worsening of parkinsonism to the possible lethal neuroleptic-malignant syndromes [2]. Yet, variances of presentation and overlapping symptoms with AD and Fronto-Temporal lobe Degeneration (FTD), could be misleading in the process of addressing a clinical diagnosis with consequent therapeutic risks(e.g. introducing neuroleptic treatments in patient with DLB), or economic costs (e.g. addressing patients with DLB to treatment protocols dedicated to AD patients, based on vaccines or antibodies against amyloid proteins, a neuropathological feature of AD). It is evident the stringent need for improvement of reliable diagnostic tools (u.e. biomarkers) to differentiate the diseases associated with dementia. In 2010 the National Institute of Health, NIH, held a symposium focused on the development of possible biomarkers for DLB. Among the different suggested biomarkers, neurophysiological assessments were reconsidered, as a large amount of neurophysiological studies had been devoted to AD and PD, whose characteristics are shared by DLB. www.intechopen.com Neuroimaging for Clinicians -Combining Research and Practice 300We contributed to several studies on this argument along the years, and in the present chapter we discuss the role of clinical neurophysiological studies in DLB in comparison with other disorders. The essential background of our original studies laid in the fact that most historical studies were performed when the DLB clinical entity was unknown and therefore some of the past results were marred by absent recognition of this clinical entity. Synucleinopathies: Dementia with lewy bodiesSynucleinopathies comprise a diverse groups of neurodegenerati...

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Striatal monoamine terminals in Lewy body dementia and Alzheimer's disease

Cited by 59 publications

References 38 publications

In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with ¹⁸F-AV-133

In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with ¹⁸F-AV-133

The ¹⁸F-FDG PET Cingulate Island Sign and Comparison to ¹²³I-β-CIT SPECT for Diagnosis of Dementia with Lewy Bodies

Is There a Place for Clinical Neurophysiology Assessments in Synucleinopathies?

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Striatal monoamine terminals in Lewy body dementia and Alzheimer's disease

Cited by 59 publications

References 38 publications

In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with 18F-AV-133

In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with 18F-AV-133

The 18F-FDG PET Cingulate Island Sign and Comparison to 123I-β-CIT SPECT for Diagnosis of Dementia with Lewy Bodies

Is There a Place for Clinical Neurophysiology Assessments in Synucleinopathies?

Contact Info

Product

Resources

About

In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with ¹⁸F-AV-133

In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with ¹⁸F-AV-133

The ¹⁸F-FDG PET Cingulate Island Sign and Comparison to ¹²³I-β-CIT SPECT for Diagnosis of Dementia with Lewy Bodies