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Molecular imaging biomarkers for dementia with Lewy bodies: an update

Published online by Cambridge University Press:  22 December 2014

Elizabeta B. Mukaetova-Ladinska
Elizabeta B. Mukaetova-Ladinska*
Affiliation:
Newcastle University, Newcastle upon Tyne, UK
*
Correspondence should be addressed to: E. B. Mukaetova-Ladinska, Institute of Neuroscience and Newcastle University Institute for Ageing Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK. Phone: +44 191 246 8777/+44 191 282 0045; Fax: +44 191 282 4839. Email: [email protected].
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Abstract

Background:

Dementia with Lewy body (DLB) is considered to be the second most common form of neurodegenerative disorders after Alzheimer's disease (AD), affecting as many as 100,000 people in the UK and up to 1.3 million in the USA. However, nearly half of patients with DLB remain undiagnosed thus depriving many of them from an early and adequate treatment of their distressing symptoms. Accurate and early diagnosis of DLB is important for both patients and their caregivers, since the neuropsychiatric symptoms require specific management.

Methods:

In the current study, we review the most recent developments in the field of molecular nuclear imaging to diagnose DLB.

Results:

The review addresses, the neurotransmitter based (dopaminergic, cholinergic, and glutamatergic) nuclear imaging techniques, role of the autonomic dysfunction and its visualization in DLB with myocardial sympathetic imaging and vesicular catecholamine uptake, as well as the use of amyloid polypeptides and glial markers as molecular imaging probes in the clinical diagnosis of DLB.

Conclusions:

Most of the above nuclear imaging methods are restricted to highly specialized clinical centers, and thus not applicable to a large number of patients requiring dementia (e.g. DLB) diagnosis in routine clinical setting. Validating them against more readily accessible peripheral biomarkers, e.g. CSF and blood biomarkers linked to the DLB process, may facilitate their use in wider clinical settings.

Keywords

dementia with Lewy bodyimagingneurotransmitterdopamineacetylcholineglutamatemyocardial sympathetic imagingvesicular catecholamineamyloid peptidesamyloid-betagliaα-synuclein
Type
Review Article
Information
International Psychogeriatrics , Volume 27 , Issue 4 , April 2015 , pp. 555 - 577
Copyright
Copyright © International Psychogeriatric Association 2014 

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References

Aarsland, D. et al. (2009). Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurology, 8, 613–618.Google Scholar
Aerts, M. B., Esselink, R. A., Claassen, J. A., Abdo, W. F., Bloem, B. R. and Verbeek, M. M. (2011). CSF tau, Aβ42, and MHPG differentiate dementia with Lewy bodies from Alzheimer's disease. Journal of Alzheimer's Disease, 27, 377–384.Google Scholar
Albasanz, J. L., Dalfó, E., Ferrer, I. and Martín, M. (2005). Impaired metabotropic glutamate receptor/phospholipase C signalling pathway in the cerebral cortex in Alzheimer's disease and dementia with Lewy bodies correlates with stage of Alzheimer's-disease-related changes. Neurobiology of Disease, 20, 685–693.Google Scholar
Andersson, M., Zetterberg, H., Minthon, L., Blennow, K. and Londos, E. (2011). The cognitive profile and CSF biomarkers in dementia with Lewy bodies and Parkinson's disease dementia. International Journal of Geriatric Psychiatry, 26, 100–105.Google Scholar
Bagchi, D. P. et al. (2013). Binding of the radioligand SIL23 to α-synuclein fibrils in Parkinson disease brain tissue establishes feasibility and screening approaches for developing a Parkinson disease imaging agent. Public Library of Science One, 8, e55031.Google Scholar
Ballard, C., Aarsland, D., Francis, P. and Corbett, A. (2013). Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodies: pathophysiology, clinical features, and pharmacological management. Drugs & Aging, 30, 603–611.Google Scholar
Banzo, I. et al. (2014). Amyloid imaging with (11)C-PIB PET/CT and glucose metabolism with (18)F-FDG PET/CT in a study on cognitive impairment in the clinical setting. Nuclear Medicine Communications, 35, 238–244.CrossRefGoogle Scholar
Baskys, A. (2004). Lewy body dementia: the litmus test for neuroleptic sensitivity and extrapyramidal symptoms. Journal of Clinical Psychiatry, 65 (Suppl. 11), 16–22.Google Scholar
Berti, V., Pupi, A. and Mosconi, L. (2011). PET/CT in diagnosis of dementia. Annals of the New Your Academy of Sciences, 1228, 81–92.Google Scholar
Bieschke, J. et al. (2010). EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Proceedings of the National Academy of Sciences of the United States of America, 107, 17710–17715.Google Scholar
Biomarkers Definitions Working Group (2001). Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clinical Pharmacology & Therapeutics, 69, 89–95.Google Scholar
Bittner, V. et al. (2011). Positive FP-CIT SPECT (DaTSCAN) in clinical Alzheimer's disease – an unexpected finding? Dementia and Geriatric Cognitive Disorders, 1, 283–291.Google Scholar
Blennow, K. (2010). Biomarkers in Alzheimer's disease drug development. Nature Medicine, 16, 1218–1222.Google Scholar
Bohr, I. J. et al. (2005). Cholinergic nicotinic receptor involvement in movement disorders associated with Lewy body diseases. An autoradiography study using [(125)I]alpha-conotoxinMII in the striatum and thalamus. Experimental Neurology, 191, 292–300.Google Scholar
Boot, B. P. et al. (2013). Risk factors for dementia with Lewy bodies. A case-control study. Neurology, 81, 833–840.Google Scholar
Bosboom, J. L. W. and Wolters, E. (2004). Psychotic symptoms in Parkinson's disease: pathophysiology and management. Expert Opinion on Drug Safety, 3, 209–220.Google Scholar
Brooks, D. and Halliday, G. M. (2009). Intralaminar nuclei of the thalamus in Lewy body diseases. Brain Research Bulletin, 78, 97–104.Google Scholar
Burke, J. F. et al. (2011). Assessment of mild dementia with amyloid and dopamine terminal positron emission tomography. Brain, 134, 1647–1657.Google Scholar
Burton, E. J. et al. (2009). Medial temporal lobe atrophy on MRI differentiates Alzheimer's disease from dementia with Lewy bodies and vascular cognitive impairment: a prospective study with pathological verification of diagnosis. Brain, 132, 195–203.Google Scholar
Cagnin, A. et al. (2001). In-vivo measurement of activated microglia in dementia. Lancet, 358, 461–467.Google Scholar
Camacho, V. et al. (2011). Cardiac sympathetic impairment parallels nigrostriatal degeneration in probable dementia with Lewy bodies. The Quarterly Journal of Nuclear Medicine and Molecular Imaging, 55, 476–483.Google ScholarPubMed
Chang, E. et al. (2009). Modulation and detection of tau aggregation with small-molecule ligands. Current Alzheimer Research, 6, 409–414.Google Scholar
Chirumamilla, A. and Travin, M. I. (2011). Cardiac applications of 123I-mIBG imaging. Seminars in Nuclear Medicine, 41, 374–387.Google Scholar
Clinton, L. K., Blurton-Jones, M., Myczek, K., Trojanowski, J. Q. and LaFerla, F. M. (2010). Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. The Journal of Neuroscience, 30, 7281–7289.Google Scholar
Colloby, S. J., McParland, S., O’Brien, J. T. and Attems, J. (2012). Neuropathological correlates of dopaminergic imaging in Alzheimer's disease and Lewy body dementias. Brain, 135, 2798–2808.Google Scholar
Colloby, S. J., O’Brien, J. T. and Taylor, J. P. (2014). Patterns of cerebellar volume loss in dementia with Lewy bodies and Alzheimer dementia with Lewy bodies: a VBM-DARTEL study. Psychiatry Research, 223, 187–191.Google Scholar
Colloby, S. J. et al. (2006). In vivo SPECT imaging of muscarinic acetylcholine receptors using (R,R) 123I-QNB in dementia with Lewy bodies and Parkinson's disease dementia. Neuroimage, 33, 423–429.Google Scholar
Colloby, S. J. et al. (2010). Nicotinic 123I-5IA-85380 single photon emission computed tomography as a predictor of cognitive progression in Alzheimer's disease and dementia with Lewy bodies. American Journal of Geriatric Psychiatry, 18, 86–90.Google Scholar
Colloby, S. J. et al. (2013). Multivariate spatial covariance analysis of 99mTc-exametazime SPECT images in dementia with Lewy bodies and Alzheimer's disease: utility in differential diagnosis. Journal of Cerebral Blood Flow and Metabolism, 33, 612–618.Google Scholar
Court, J. et al. (1999). Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: alpha-bungarotoxin and nicotine binding in the thalamus. Journal of Neurochemistry, 73, 1590–1597.Google Scholar
Cummings, J. L. et al. (2011). The role of dopaminergic imaging in patients with symptoms of dopaminergic system neurodegeneration. Brain, 134, 3146–3166.Google Scholar
Dalfó, E., Albasanz, J. L., Martin, M. and Ferrer, I. (2004). Abnormal metabotropic glutamate receptor expression and signalling in the cerebral cortex in diffuse Lewy body disease is associated with irregular alpha-synuclein/phospholipase C (PLCbeta1) interactions. Brain Pathology, 14, 388–398.Google Scholar
David, R. et al. (2008). Striatal dopamine transporter levels correlate with apathy in neurodegenerative diseases a SPECT study with partial volume effect correction. Clinical Neurology and Neurosurgery, 110, 19–24.Google Scholar
Davis, D. H. et al. (2012). Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study. Brain, 135, 2809–2816.Google Scholar
Davison, C. M. and O’Brien, J. T. (2014). A comparison of FDG-PET and blood flow SPECT in the diagnosis of neurodegenerative dementias: a systematic review. International Journal of Geriatric Psychiatry, 29, 551–561.Google Scholar
Delli Pizzi, S. et al. (2014). Thalamic involvement in fluctuating cognition in dementia with Lewy bodies: magnetic resonance evidences. Cerebral Cortex, pii: bhu220. (Epub ahead of print)Google ScholarPubMed
Del Ser, T., Hachinski, V., Merskey, H. and Munoz, D. G. (2001). Clinical and pathologic features of two groups of patients with dementia with Lewy bodies: effect of coexisting Alzheimer-type lesion load. Alzheimer Disease and Associated Disorders, 15, 31–44.Google Scholar
Dickens, A. M. et al. (2014). Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180. Journal of Nuclear Medicine, 55, 466–472.Google Scholar
Donaghy, P., Thomas, A. J. and O’Brien, J. T. (2013). Amyloid PET imaging in lewy body disorders. American Journal of Geriatric Psychiatry, pii: S1064-7481(13)00168-1.Google Scholar
Doorn, K. J. et al. (2014). Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson's disease patients. Acta Neuropathologica Communications, 7, 90.Google Scholar
Eberling, J. L., Dave, K. D. and Frasier, M. A. (2013). α-Synuclein Imaging: a critical need for Parkinson's disease research. Journal of Parkinson's Disease, 3, 565–567.Google Scholar
Edison, P. et al. (2008). Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. Journal of Neurology, Neurosurgery and Psychiatry, 79, 1331–1338.Google Scholar
Ferman, T. J. et al. (2004). DLB fluctuations: specific features that reliably differentiate from AD and normal aging. Neurology, 62, 181–187.Google Scholar
Ferman, T. J. et al. (2013). Pathology and temporal onset of visual hallucinations, misperceptions and family misidentification distinguishes dementia with Lewy bodies from Alzheimer's disease. Parkinsonism and Related Disorders, 19, 227–231.Google Scholar
Florea, I. (2008). PET Parametric imaging of acetylcholine esterase activity without arterial blood sampling in normal subjects and patients with neurodegenerative disease. University of Padova (PhD thesis)Google Scholar
Fodero-Tavoletti, M. T. et al. (2011). 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer's disease. Brain, 134, 1089–1100.Google Scholar
Francis, P. T. (2009). Altered glutamate neurotransmission and behaviour in dementia: evidence from studies of memantine. Current Molecular Pharmacology, 2, 77–82.Google Scholar
Francis, P. T. and Perry, E. K. (2007). Cholinergic and other neurotransmitter mechanisms in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies. Movement Disorders, 22 (Suppl. 17), S351–S357.Google Scholar
Fujinaga, M. et al. (2012). Development of N-[4-[6-(Isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[(11)C]methylbenzamide for positron emission tomography imaging of metabotropic glutamate 1 receptor in monkey brain. Journal of Medicinal Chemistry, 55, 11042–11051.Google Scholar
Fujishiro, H., Nakamura, S., Kitazawa, M., Sato, K. and Iseki, E. (2012). Early detection of dementia with Lewy bodies in patients with amnestic mild cognitive impairment using 123I-MIBG cardiac scintigraphy. Journal of Neurological Sciences, 315, 115–119.Google Scholar
Gallagher, D. A. et al. (2011). Testing an aetiological model of visual hallucinations in Parkinson's disease. Brain, 134, 3299–3309.Google Scholar
Galvin, J. E. et al. (2010). Lewy body dementia: caregiver burden and unmet needs. Alzheimer Disease and Associated Disorders, 24, 177–181.Google Scholar
Gerhard, A. et al. (2006). In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiology of Disease, 21, 404–412.Google Scholar
Geser, F., Wenning, G. K., Poewe, W. and McKeith, I. (2005). How to diagnose dementia with Lewy bodies: state of the art. Movement Disorders, 20, S11–S20.Google Scholar
Goldstein, D. S., Holmes, C., Kopin, I. J. and Sharabi, Y. (2011). Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases. Journal of Clinical Investigation, 121, 3320–3330.Google Scholar
Gómez-Tortosa, E., Irizarry, M. C., Gómez-Isla, T. and Hyman, B. T. (2000). Clinical and neuropathological correlates of dementia with Lewy bodies. Annals of the New York Academy of Sciences, 920, 9–15.Google Scholar
Gomperts, S. N. et al. (2008). Imaging amyloid deposition in Lewy body diseases. Neurology, 71, 903–910.Google Scholar
Hamilton, J.M., Landy, K.M., Salmon, D.P., Hansen, L.A., Masliah, E. and Galasko, D. (2012). Early visuospatial deficits predict the occurrence of visual hallucinations in autopsy-confirmed dementia with Lewy bodies. American Journal of Geriatric Psychiatry, 20, 773–781.Google Scholar
Hampel, H. et al. (2011). Biomarkers for Alzheimer's disease therapeutic trials. Progress in Neurobiology, 95, 579–593.Google Scholar
Hanyu, H., Sato, T., Hirao, K., Kanetaka, H., Sakurai, H. and Iwamoto, T. (2009). Differences in clinical course between dementia with Lewy bodies and Alzheimer's disease. European Journal of Neurology, 16, 212–217.Google Scholar
Harding, A. J., Broe, G. A. and Halliday, G. M. (2002a). Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain, 125, 391–403.Google Scholar
Harding, A. J., Stimson, E., Henderson, J. M. and Halliday, G. M. (2002b). Clinical correlates of selective pathology in the amygdala of patients with Parkinson's disease. Brain, 125, 2431–2445.Google Scholar
Hasegawa, N. et al. (2013). Prevalence of delirium among outpatients with dementia. International Psychogeriatrics, 25, 1877–1883.Google Scholar
Herholz, K. et al. (2000). In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism. Journal of Neural Transmission, 107, 1457–1468.Google Scholar
Iannaccone, S. et al. (2013). In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson's disease. Parkinsonism and Related Disorders, 19, 47–52.Google Scholar
Inui, Y., Toyama, H., Manabe, Y., Sarai, M. and Iwata, N. (2014). Comparison of (123)I-MIBG myocardial scintigraphy, brain perfusion SPECT, and voxel-based MRI morphometry for distinguishing between dementia with Lewy bodies and Alzheimer's disease. Annals of Nuclear Medicine, 28, 796–804.Google Scholar
Iranzo, A. et al. (2013). Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurology, 12, 443–453.Google Scholar
Jicha, G. A. et al. (2010). Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease. Neurobiology of Aging, 31, 1805–1813.Google Scholar
Johnson, K. A. et al. (2013). Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. Amyloid imaging task force of the Alzheimer's association and society for nuclear medicine and molecular imaging. Alzheimer's & Dementia, 9, e106–e109.Google Scholar
Kasuga, K., Nishizawa, M. and Ikeuchi, T. (2012). α-Synuclein as CSF and blood biomarker of dementia with Lewy bodies. International Journal of Alzheimer's Disease, 2012, 437,025.Google Scholar
Kemp, P. M., Clyde, K. and Holmes, C. (2011). Impact of 123I-FP-CIT (DaTSCAN) SPECT on the diagnosis and management of patients with dementia with Lewy bodies: a retrospective study. Nuclear Medicine Communications, 32, 298–302.Google Scholar
Kim, K. S. et al. (2012). Proteolytic cleavage of extracellular α-synuclein by plasmin: implications for Parkinson disease. The Journal of Biological Chemistry, 287, 24862–24872.Google Scholar
Klein, J. C. et al. (2010). Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo . Neurology, 74, 885–892.Google Scholar
Klunk, W. E. et al. (2005). Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer's disease brain but not in transgenic mouse brain. The Journal of Neuroscience, 25, 10598–10606.Google Scholar
Kobayashi, S., Tateno, M., Morii, H., Utsumi, K. and Saito, T. (2009). Decreased cardiac MIBG uptake, its correlation with clinical symptoms in dementia with Lewy bodies. Psychiatry Research, 174, 76–80.Google Scholar
Leung, K. (2013). N-(4-(6-(Isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N-methyl-4-[11C]methylbenzamide. Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. (updated 2013 May 02).Google Scholar
Litvan, I. et al. (1998). Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study. Archives of Neurology, 55, 969–978.Google Scholar
Lockhart, A. et al. (2003). The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant alpha1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker. Nuclear Medicine and Biology, 30, 199–206.Google Scholar
Mackenzie, I. R. (2000). Activated microglia in dementia with Lewy bodies. Neurology, 55, 132–134.Google Scholar
Maetzler, W. et al. (2011). Serum and cerebrospinal fluid uric acid levels in lewy body disorders: associations with disease occurrence and amyloid-β pathway. Journal of Alzheimer's Disease, 27, 119–126.Google Scholar
Mak, E., Su, L., Williams, G. B. and O’Brien, J. T. (2014). Neuroimaging characteristics of dementia with Lewy bodies. Alzheimers Research & Therapy, 6, 18.Google Scholar
Marcone, A. et al. (2012). [11C]-MP4A PET cholinergic measurements in amnestic mild cognitive impairment, probable Alzheimer's disease, and dementia with Lewy bodies: a bayesian method and voxel-based analysis. Journal of Alzheimer's Disease, 31, 387–399.Google Scholar
Masliah, E. et al. (2001). beta-Amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America, 98, 12245–12250.Google Scholar
McKeith, I. et al. (2007). Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurology, 6, 305–313.CrossRefGoogle ScholarPubMed
McKeith, I.G. et al. (1996). Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology, 47, 1113–1124.Google Scholar
McKeith, I. G. et al. (2005). Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology, 65, 1863–1872.Google Scholar
McKhann, G. M. et al. (2011). The diagnosis of dementia due to Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia, 7, 26–3269.Google Scholar
Molina, J. A et al. (2005). Neurotransmitter amino acid in cerebrospinal fluid of patients with dementia with Lewy bodies. Journal of Neural Transmission, 112, 557–563.Google Scholar
Morgan, S. et al. (2012). Differentiation of frontotemporal dementia from dementia with Lewy bodies using FP-CIT SPECT. Journal of Neurology, Neurosurgery and Psychiatry, 83, 1063–1070.Google Scholar
Mortimer, A. M., Likeman, M. and Lewis, T. T. (2013). Neuroimaging in dementia: a practical guide. Practical Neurology, 13, 92–103.Google Scholar
Mukaetova-Ladinska, E. B. et al. (2009). Lewy body variant of Alzheimer's disease: selective neocortical loss of t-SNARE proteins and loss of MAP2 and alpha-synuclein in medial temporal lobe. The Scientific World Journal, 9, 1463–1475 Google Scholar
Mukaetova-Ladinska, E. B. et al. (2013). Synaptic proteins and choline acetyltransferase loss in visual cortex in dementia with Lewy bodies. Journal of Neuropathology and Experimental Neurology, 72, 53–60.Google Scholar
Nakatsuka, T., Imabayashi, E., Matsuda, H., Sakakibara, R., Inaoka, T. and Terada, H. (2013). Discrimination of dementia with Lewy bodies from Alzheimer's disease using voxel-based morphometry of white matter by statistical parametric mapping 8 plus diffeomorphic anatomic registration through exponentiated Lie algebra. Neuroradiology, 55, 559–566.Google Scholar
Neal, K. L. et al. (2013). Development and screening of contrast agents for in vivo imaging of Parkinson's disease. Molecular Imaging and Biology, 15, 585–595.Google Scholar
O’Brien, J. T. et al. (2008). Nicotinic alpha4beta2 receptor binding in dementia with Lewy bodies using 123I-5IA-85380 SPECT demonstrates a link between occipital changes and visual hallucinations. Neuroimage, 40, 1056–1063.Google Scholar
O’Brien, J. T. et al. (2009). Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies. British Journal of Psychiatry, 194, 34–39.Google Scholar
O’Brien, J. T. et al. (2014). Is ioflupane I123 injection diagnostically effective in patients with movement disorders and dementia? Pooled analysis of four clinical trials. British Medical Journal Open, 4, e005122.Google Scholar
Oda, H. et al. (2013). Myocardial scintigraphy may predict the conversion to probable dementia with Lewy bodies. Neurology, 81, 1741–1745.Google Scholar
Oinas, M. et al. (2009). Neuropathologic findings of dementia with lewy bodies (DLB) in a population-based Vantaa 85+ study. Journal of Alzheimer's Disease, 18, 677–689.Google Scholar
Okamura, N. et al. (2010). In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with (18)F-AV-133. Journal of Nuclear Medicine, 51, 223–228.Google Scholar
Palmqvist, S., Hansson, O., Minthon, L. and Londos, E. (2009). Practical suggestions on how to differentiate dementia with Lewy bodies from Alzheimer's disease with common cognitive tests. International Journal of Geriatric Psychiatry, 24, 1405–1412.Google Scholar
Papathanasiou, N. D., Boutsiadis, A., Dickson, J. and Bomanji, J. B. (2012). Diagnostic accuracy of 123I-FP-CIT (DaTSCAN) in dementia with Lewy bodies: a meta-analysis of published studies. Parkinsonism and Related Disorders, 18, 225–229.Google Scholar
Peavy, G. M. et al. (2013). Neuropsychiatric features of frontal lobe dysfunction in autopsy-confirmed patients with lewy bodies and “pure” Alzheimer disease. American Journal of Geriatric Psychiatry, 21, 509–519.Google Scholar
Peraza, L. R. et al. (2014). fMRI resting state networks and their association with cognitive fluctuations in dementia with Lewy bodies. Neuroimage Clinical, 4, 558–565.Google Scholar
Pimlott, S. L. et al. (2004). Nicotinic acetylcholine receptor distribution in Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease, and vascular dementia: in vitro binding study using 5-[(125)i]-a-85380. Neuropsychopharmacology, 29, 108–116.Google Scholar
Price, D. L. et al. (2010). Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy-implications for excitotoxicity. Public Library of Science One, 5, e14020.Google Scholar
Prüss, H. et al. (2012). IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment. Neurology, 78, 1743–1753.Google Scholar
Rahkonen, T., Luukkainen-Markkula, R., Paanila, S., Sivenius, J. and Sulkava, R. (2000). Delirium episode as a sign of undetected dementia among community dwelling elderly subjects: a 2 year follow up study. Journal of Neurology, Neurosurgery and Psychiatry, 69, 519–521.Google Scholar
Ray, M. et al. (2004). Involvement of alpha6/alpha3 neuronal nicotinic acetylcholine receptors in neuropsychiatric features of dementia with Lewy bodies: [(125)I]-alpha-conotoxin MII binding in the thalamus and striatum. Neuroscience Letters, 372, 220–225.Google Scholar
Reesink, F. E. et al. (2010). CSF α-synuclein does not discriminate dementia with Lewy bodies from Alzheimer's disease. Journal of Alzheimer's Disease, 22, 87–95.Google Scholar
Ribeiro Morais, G., Vicente Miranda, H., Santos, I.C., Santos, I., Outeiro, T.F. and Paulo, A. (2011). Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes. Bioorganic and Medicinal Chemistry, 19, 7698–7710.Google Scholar
Ries, J. et al. (2013). Superresolution imaging of amyloid fibrils with binding-activated probes. American Chemical Society Chemical Neuroscience, 4, 1057–1061.Google Scholar
Roselli, F. et al. (2009). Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: a 123I-FP-CIT SPECT study. Movement Disorders, 24, 2097–2103.Google Scholar
Rowe, C. C. et al. (2007). Imaging beta-amyloid burden in aging and dementia. Neurology, 68, 1718–1725.Google Scholar
Sakakibara, R. et al. (2012). Amnestic mild cognitive impairment with low myocardial metaiodobenzylguanidine uptake. American Journal of Neurodegenerative Disease, 1, 146–151.Google Scholar
Samuel, W., Alford, M., Hofstetter, C. R. and Hansen, L. (1997). Dementia with Lewy bodies versus pure Alzheimer disease: differences in cognition, neuropathology, cholinergic dysfunction, and synapse density. Journal of Neuropathology and Experimental Neurology, 56, 499–508.Google Scholar
Santangelo, A. et al. (2010). The clinical and rehabilitative complexity in dementia with Lewy bodies (DLB): experience on a random sample of elderly patients dwelling in an RSA (“Residenza Sanitaria Assistita”) of catania. Archives of Gerontology and Geriatrics, 51, e7–e10.Google Scholar
Schuitemaker, A. et al. (2013). Microglial activation in Alzheimer's disease: an (R)-[11C]PK11195 positron emission tomography study. Neurobiology of Aging, 34, 128–136.Google Scholar
Sharma, S. et al. (2013). Biomarkers in Parkinson's disease (recent update). Neurochemistry International, 63, 201–229.CrossRefGoogle ScholarPubMed
Shimada, H. et al. (2009). Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. Neurology, 73, 273–278.Google Scholar
Shoji, M. (2011). Biomarkers of the dementia. International Journal of Alzheimer's Disease, 2011, 564321.Google Scholar
Siderowf, A. et al. (2014). PET imaging of amyloid with florbetapir F 18 and PET imaging of dopamine degeneration with 18F-AV-133 (florbenazine) in patients with Alzheimer's disease and Lewy body disorders. BioMedCentral Neurology, 14, 79.Google Scholar
Siepel, F. J. et al. (2013). (123I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study. British Medical Journal Open, 3, doi:pii: e002642.Google Scholar
Sinha, N., Firbank, M. and O’Brien, J. T. (2012). Biomarkers in dementia with Lewy bodies: a review. International Journal of Geriatric Psychiatry, 27, 443–453.Google Scholar
Sohma, H. et al. (2013). Evaluation of annexin A5 as a biomarker for Alzheimer's disease and dementia with lewy bodies. Frontiers in Aging Neuroscience, 5, 15.Google Scholar
Spehl, T. S. et al. (2014). Syndrome-specific patterns of regional cerebral glucose metabolism in posterior cortical atrophy in comparison to dementia with Lewy bodies and Alzheimer's disease-A [F-18]-Fdg pet study. Journal of Neuroimaging, doi: 10.1111/jon.12104. [Epub ahead of print]Google Scholar
Stefanelli, A., Treglia, G., Bruno, I., Rufini, V. and Giordano, A. (2013). Pharmacological interference with 123I-metaiodobenzylguanidine: a limitation to developing cardiac innervation imaging in clinical practice? European Review for Medical and Pharmacological Sciences, 17, 1326–1333.Google Scholar
Stern, Y. et al. (2001). An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease. Archives of Neurology, 58, 460–465.Google Scholar
Tatsch, K. (2008). Imaging of the dopaminergic system in differential diagnosis of dementia. European Journal of Nuclear Medicine and Molecular Imaging, 35, (Suppl. 1), S51–S57.Google Scholar
Tiraboschi, P. and Guerra, U. P. (2010). How to distinguish dementia with Lewy bodies from Alzheimer disease? The Open Nuclear Medicine Journal, 2, 58–62.Google Scholar
Tiwari, A. K. et al. (2014). Characterization of a novel acetamidobenzoxazolone-based PET ligand for translocator protein (18 kDa) imaging of neuroinflammation in the brain. Journal of Neurochemistry, 129, 712–720.Google Scholar
Toru, S. et al. (2010). Depletion or preservation of cardiac sympathetic nerve - an autopsy-verified contrast in two cases of Alzheimer's disease with or without Lewy bodies. European Neurology, 64, 129–133.Google Scholar
Treglia, G. and Cason, E. (2012). Diagnostic performance of myocardial innervation imaging using MIBG scintigraphy in differential diagnosis between dementia with lewy bodies and other dementias: a systematic review and a meta-analysis. Journal of Neuroimaging, 22, 111–117.Google Scholar
Treglia, G. et al. (2014). Iodine-123 metaiodobenzylguanidine scintigraphy and iodine-123 ioflupane single photon emission computed tomography in Lewy body diseases: complementary or alternative techniques? Journal of Neuroimaging, 24, 149–154.Google Scholar
Tripathi, M. et al. (2014). Differential diagnosis of neurodegenerative dementias using metabolic phenotypes on F-18 FDG PET/CT. The Neuroradiology Journal, 27, 13–21.Google Scholar
Vann Jones, S. A. and O’Brien, J. T. (2013). The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychological Medicine, 25, 1–11.Google Scholar
Villemagne, V. L. et al. (2011). In vivo assessment of vesicular monoamine transporter type 2 in dementia with lewy bodies and Alzheimer disease. Archives of Neurology, 68, 905–912.Google Scholar
Villemagne, V. L. et al. (2012). Differential diagnosis in Alzheimer's disease and dementia with Lewy bodies via VMAT2 and amyloid imaging. Neurodegenerative Diseases, 10, 161–165.Google Scholar
Walker, Z. and Cummings, J. L. (2012). [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography brain imaging in the diagnosis of dementia with Lewy bodies. Alzheimer's & Dementia, 8, 74–83.Google Scholar
Warr, L. and Walker, Z. (2012). Identification of biomarkers in Lewy-body disorders. Quarterly Journal of Nuclear Medicine and Molecular Imaging, 56, 39–54.Google Scholar
Watson, R., Colloby, S. J., Blamire, A. M. and O’Brien, J. T. (2014). Assessment of regional gray matter loss in dementia with Lewy bodies: a surface-based MRI analysis. American Journal of Geriatric Psychiatry, pii: S1064-7481(14)00219-X.Google Scholar
Xia, C. F. et al. (2013). [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimer's & Dementia, 9, 666–676.Google Scholar
Yamamoto, R. et al. (2006). Investigation of Lewy pathology in the visual pathway of brains of dementia with Lewy bodies. Journal of Neurological Sciences, 246, 95–101.Google Scholar
Yamasaki, T. et al. (2014). Noninvasive quantification of metabotropic glutamate receptor type 1 with [11C]ITDM: a small-animal PET study. Journal of Cerebral Blood Flow and Metabolism, 34, 606–612.Google Scholar
Yasuno, F. et al. (2012). Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [11C]DAA1106. Psychiatry Research, 203, 67–74.Google Scholar
Yeo, J. M., Lim, X., Khan, Z. and Pal, S. (2013). Systematic review of the diagnostic utility of SPECT imaging in dementia. European Archives of Psychiatry and Clinical Neuroscience, 263, 539–552.Google Scholar
Yokoyama, K. et al. (2013). Milnacipran influences the indexes of I-metaiodobenzylguanidine scintigraphy in elderly depressed patients. Psychiatry and Clinical Neurosciences, 68, 169–175.Google Scholar
Yoshizawa, H., Vonsattel, J. P. and Honig, L. S. (2013). Early neuropsychological discriminants for Lewy body disease: an autopsy series. Journal of Neurology, Neurosurgery and Psychiatry, 84, 1326–1330.Google Scholar
Zaccai, J., McCracken, C. and Brayne, C. (2005). A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age and Ageing, 34, 561–566.Google Scholar
Ziebell, M. et al. (2013). Striatal dopamine transporter binding does not correlate with clinical severity in dementia with Lewy bodies. Journal of Nuclear Medicine, 54, 1072–1076.Google Scholar
Zupancic, M., Mahajan, A. and Handa, K. (2011). Dementia with Lewy bodies: diagnosis and management for primary care providers. The Primary Care companion for the CNS Disorders, 13 (5). pii: PCC.11r01190. doi: 10.4088/PCC.11r01190.Google Scholar