Amyloid PET Imaging in Lewy Body Disorders
2013; Elsevier BV; Volume: 23; Issue: 1 Linguagem: Inglês
10.1016/j.jagp.2013.03.001
ISSN1545-7214
AutoresPaul C. Donaghy, Alan Thomas, John T. O’Brien,
Tópico(s)Dementia and Cognitive Impairment Research
ResumoLewy body (LB) disorders, including Parkinson disease (PD), Parkinson disease dementia (PDD), and dementia with Lewy bodies (DLB), are the second most common type of neurodegenerative dementia. Although the pathological hallmarks of LB disorders are Lewy bodies and Lewy neurites, cortical amyloid-beta (Aβ) deposition is also often seen. The relationship between Aβ pathology and dementia in LB disorders is unclear. Recently, positron emission tomography Aβ ligands have been developed that enable in vivo imaging of Aβ. In this paper we review amyloid imaging studies in LB disorders. LB disorders are associated with lower mean cortical Aβ ligand binding compared with Alzheimer disease. In DLB and PDD many subjects have normal levels of cortical Aβ, though a subset show increased Aβ ligand binding. Those with DLB show greater ligand binding than PDD; binding does not appear to be increased in PD without dementia. Cortical Aβ deposition may be a factor in the development of cognitive impairment in some cases of dementia in LB disorders. Amyloid imaging is of limited use in the diagnosis of LB disorders but Aβ deposition may predict the future development of dementia in PD. Reports of correlation between Aβ deposition and symptom profile, severity, and progression have been inconsistent. Some results suggest a synergistic interaction between Aβ and α-synuclein. Interpretation of the current evidence is hampered by differing methodologies across studies and small sample sizes. Large, prospective longitudinal studies are needed to clarify the association of Aβ with symptom development, progression, severity, and treatment response in LB disorders. Lewy body (LB) disorders, including Parkinson disease (PD), Parkinson disease dementia (PDD), and dementia with Lewy bodies (DLB), are the second most common type of neurodegenerative dementia. Although the pathological hallmarks of LB disorders are Lewy bodies and Lewy neurites, cortical amyloid-beta (Aβ) deposition is also often seen. The relationship between Aβ pathology and dementia in LB disorders is unclear. Recently, positron emission tomography Aβ ligands have been developed that enable in vivo imaging of Aβ. In this paper we review amyloid imaging studies in LB disorders. LB disorders are associated with lower mean cortical Aβ ligand binding compared with Alzheimer disease. In DLB and PDD many subjects have normal levels of cortical Aβ, though a subset show increased Aβ ligand binding. Those with DLB show greater ligand binding than PDD; binding does not appear to be increased in PD without dementia. Cortical Aβ deposition may be a factor in the development of cognitive impairment in some cases of dementia in LB disorders. Amyloid imaging is of limited use in the diagnosis of LB disorders but Aβ deposition may predict the future development of dementia in PD. Reports of correlation between Aβ deposition and symptom profile, severity, and progression have been inconsistent. Some results suggest a synergistic interaction between Aβ and α-synuclein. Interpretation of the current evidence is hampered by differing methodologies across studies and small sample sizes. Large, prospective longitudinal studies are needed to clarify the association of Aβ with symptom development, progression, severity, and treatment response in LB disorders. Lewy body (LB) disorders include Parkinson disease (PD) and the Lewy body dementias, dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). Following Alzheimer disease (AD), LB dementias are the second most common cause of neurodegenerative dementia, with DLB alone accounting for around 15% of cases at postmortem1McKeith I.G. Galasko D. Kosaka K. et al.Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.Neurology. 1996; 47: 1113-1124Crossref PubMed Scopus (3598) Google Scholar and 10% in clinical samples,2Stevens T. Livingston G. Kitchen G. et al.Islington study of dementia subtypes in the community.Br J Psychiatry. 2002; 180: 270-276Crossref PubMed Scopus (170) Google Scholar and high rates of dementia observed in PD.3Emre M. Aarsland D. Brown R. et al.Clinical diagnostic criteria for dementia associated with Parkinson's disease.Mov Disord. 2007; 22 (quiz 1837): 1689-1707Crossref PubMed Scopus (1992) Google Scholar DLB and PDD are both characterized by dementia syndromes with specific associated symptoms including parkinsonism, fluctuating cognition, and visual hallucinations.3Emre M. Aarsland D. Brown R. et al.Clinical diagnostic criteria for dementia associated with Parkinson's disease.Mov Disord. 2007; 22 (quiz 1837): 1689-1707Crossref PubMed Scopus (1992) Google Scholar, 4McKeith I.G. Dickson D.W. Lowe J. et al.Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.Neurology. 2005; 65: 1863-1872Crossref PubMed Scopus (4084) Google Scholar Based on international consensus, DLB is diagnosed when dementia develops without parkinsonism or within a year of the development of parkinsonism; PDD is diagnosed when parkinsonism precedes dementia by more than one year.3Emre M. Aarsland D. Brown R. et al.Clinical diagnostic criteria for dementia associated with Parkinson's disease.Mov Disord. 2007; 22 (quiz 1837): 1689-1707Crossref PubMed Scopus (1992) Google Scholar, 4McKeith I.G. Dickson D.W. Lowe J. et al.Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.Neurology. 2005; 65: 1863-1872Crossref PubMed Scopus (4084) Google Scholar There are no other major clinical differences between DLB and PDD, and despite some controversy surrounding the "one-year rule" they are generally recognized to be on a continuum of LB disease.5McKeith I. Commentary: DLB and PDD: the same or different? Is there a debate?.Int Psychogeriatr. 2009; 21: 220-224Crossref PubMed Scopus (25) Google ScholarThe pathological hallmarks of LB disorders are Lewy bodies and Lewy neurites, but many cases also display AD pathology (amyloid-β [Aβ] plaques and neurofibrillary tangles [NFTs]) post mortem.6Kovari E. Horvath J. Bouras C. Neuropathology of Lewy body disorders.Brain Res Bull. 2009; 80: 203-210Crossref PubMed Scopus (52) Google Scholar The importance of AD pathology in LB disorders and its relationship to cognitive impairment is unclear. Postmortem studies of confirmed DLB cases have reported that concurrent AD pathology measured by increased NFTs was associated with a lower likelihood of visual hallucinations and a lower chance of a DLB diagnosis during life.7Merdes A.R. Hansen L.A. Jeste D.V. et al.Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies.Neurology. 2003; 60: 1586-1590Crossref PubMed Scopus (262) Google Scholar, 8Weisman D. Cho M. Taylor C. et al.In dementia with Lewy bodies, Braak stage determines phenotype, not Lewy body distribution.Neurology. 2007; 69: 356-359Crossref PubMed Scopus (83) Google Scholar A combination of AD and LB pathology in dementia is associated with a lower occurrence of parkinsonism and hallucinations compared with LB pathology alone.9Del Ser T. Hachinski V. Merskey H. et al.Clinical and pathologic features of two groups of patients with dementia with Lewy bodies: effect of coexisting Alzheimer-type lesion load.Alzheimer Dis Assoc Disord. 2001; 15: 31-44Crossref PubMed Scopus (101) Google Scholar Greater cortical Aβ pathology has been associated with increased cognitive impairment10Nelson P.T. Kryscio R.J. Jicha G.A. et al.Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies.Neurology. 2009; 73: 1127-1133Crossref PubMed Scopus (70) Google Scholar and a shorter time from onset of parkinsonian symptoms to cognitive impairment11Ballard C. Ziabreva I. Perry R. et al.Differences in neuropathologic characteristics across the Lewy body dementia spectrum.Neurology. 2006; 67: 1931-1934Crossref PubMed Scopus (252) Google Scholar, 12Fujishiro H. Iseki E. Higashi S. et al.Distribution of cerebral amyloid deposition and its relevance to clinical phenotype in Lewy body dementia.Neurosci Lett. 2010; 486: 19-23Crossref PubMed Scopus (46) Google Scholar, 13Selikhova M. Williams D.R. Kempster P.A. et al.A clinico-pathological study of subtypes in Parkinson's disease.Brain. 2009; 132: 2947-2957Crossref PubMed Scopus (325) Google Scholar in LB disorders. DLB has been associated with a greater Aβ burden than PDD and PD.12Fujishiro H. Iseki E. Higashi S. et al.Distribution of cerebral amyloid deposition and its relevance to clinical phenotype in Lewy body dementia.Neurosci Lett. 2010; 486: 19-23Crossref PubMed Scopus (46) Google Scholar, 14Aarsland D. Ballard C.G. Halliday G. Are Parkinson's disease with dementia and dementia with Lewy bodies the same entity?.J Geriatr Psychiatry Neurol. 2004; 17: 137-145Crossref PubMed Scopus (162) Google Scholar, 15Jellinger K.A. Seppi K. Wenning G.K. Clinical and neuropathological correlates of Lewy body disease.Acta Neuropathol. 2003; 106 (author reply 190): 188-189Crossref PubMed Scopus (13) Google Scholar It has been suggested that the co-occurrence of AD and LB pathology represents more than coincidence, and that there may be synergism, with Aβ increasing the propensity of α-synuclein to accumulate and aggregate.16Pletnikova O. West N. Lee M.K. et al.Abeta deposition is associated with enhanced cortical alpha-synuclein lesions in Lewy body diseases.Neurobiol Aging. 2005; 26: 1183-1192Abstract Full Text Full Text PDF PubMed Scopus (177) Google ScholarPostmortem studies are by their nature cross-sectional and tend to report end-stage disease. Thus patients with initial "pure Lewy body pathology" may be found post mortem to have significant AD pathology, although this may not have been related to their initial presentation. Positron emission tomography (PET) amyloid imaging, initially with 11C-PiB (Pittsburgh compound B) and now with 18Sojkova J. Driscoll I. Iacono D. et al.In vivo fibrillar beta-amyloid detected using [11C]PiB positron emission tomography and neuropathologic assessment in older adults.Arch Neurol. 2011; 68: 232-240Crossref PubMed Scopus (91) Google ScholarF labeled compounds, was developed to measure brain Aβ burden in vivo.17Rowe C.C. Villemagne V.L. Brain amyloid imaging.J Nucl Med. 2011; 52: 1733-1740PubMed Google Scholar Postmortem studies have demonstrated that amyloid imaging with these ligands correlates well with Aβ deposition in the form of neuritic and diffuse plaques, and amyloid angiopathy.18Sojkova J. Driscoll I. Iacono D. et al.In vivo fibrillar beta-amyloid detected using [11C]PiB positron emission tomography and neuropathologic assessment in older adults.Arch Neurol. 2011; 68: 232-240Crossref PubMed Scopus (91) Google Scholar, 19Clark C.M. Schneider J.A. Bedell B.J. et al.Use of florbetapir-PET for imaging beta-amyloid pathology.JAMA. 2011; 305: 275-283Crossref PubMed Scopus (831) Google Scholar, 20Ikonomovic M.D. Klunk W.E. Abrahamson E.E. et al.Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease.Brain. 2008; 131: 1630-1645Crossref PubMed Scopus (727) Google Scholar Aβ deposition in vivo is consistently elevated in AD, and also in some healthy control subjects.21Quigley H. Colloby S.J. O'Brien J.T. PET imaging of brain amyloid in dementia: a review.Int J Geriatr Psychiatry. 2011; 26: 991-999Crossref PubMed Scopus (122) Google Scholar, 22Rosenberg P.B. Wong D.F. Edell S.L. et al.Cognition and amyloid load in Alzheimer disease imaged with florbetapir F 18(AV-45) positron emission tomography.Am J Geriatr Psychiatry. 2013; 21: 272-278Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The objective of this paper was to review all studies to date that have involved amyloid imaging in LB disorders to examine the contribution of Aβ pathology to these disorders.Terminology in this research field has been a subject of some debate.5McKeith I. Commentary: DLB and PDD: the same or different? Is there a debate?.Int Psychogeriatr. 2009; 21: 220-224Crossref PubMed Scopus (25) Google Scholar In this paper we use the terminology accepted by recent consensus statements detailed above.3Emre M. Aarsland D. Brown R. et al.Clinical diagnostic criteria for dementia associated with Parkinson's disease.Mov Disord. 2007; 22 (quiz 1837): 1689-1707Crossref PubMed Scopus (1992) Google Scholar, 4McKeith I.G. Dickson D.W. Lowe J. et al.Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.Neurology. 2005; 65: 1863-1872Crossref PubMed Scopus (4084) Google Scholar LB disorders refers to all LB pathologies (in this paper generally PD [± mild cognitive impairment], PDD, and DLB).MethodsA Medline (Web of Knowledge; 1950–present) search was carried out in January 2013. The search algorithm used was: ("Amyloid") AND ("Positron emission tomography" OR "PET") AND ("Lewy" OR "Parkinson disease"). Each word was entered both as a 'topic' and 'MeSH' term; lemmatization was used. Eighty-two English-language results were found. Titles and abstracts were then screened by two reviewers (PD and AT) to identify studies that performed amyloid brain imaging in patients with Lewy body disease. A total of 16 studies with original data were identified (Table 1 summarizes these papers). Four papers reporting postmortem findings in patients who had antemortem amyloid PET scans were also included. Two further In Press studies available online came to the authors' attention and were included. Reference lists from the selected articles were searched for any additional references not captured by the search, though none were found.Table 1Summary of PET Amyloid Imaging Studies Excluding Neuropathological Case StudiesStudyPopulationSourceScans, LigandAmyloid PET Acquisition and Image AnalysisRegions ReportedMajor FindingsRowe et al. 200730Rowe C.C. Ng S. Ackermann U. et al.Imaging beta-amyloid burden in aging and dementia.Neurology. 2007; 68: 1718-1725Crossref PubMed Scopus (910) Google Scholar10 DLB17 AD9 MCI6 FTD27 HCAD/DLB: memory disorders and neurobehavioural clinics.Controls: from a separate longitudinal study known to have normal cognitive function.MRI11C-PIB PET90 min acquisition. ROI 11C-PIB DVR v. cerebellum. Logan graphical analysis method.16 cortical and subcortical areas including overall cortex.PiB burden AD>DLB>HC.PiB burden correlated with shorter time from onset of symptoms to diagnosis in DLB.ApoE4 genotype linked to Aβ burden across groups.Edison et al. 200823,aIncludes 10 DLB patients from Rowe et al.3013 DLBaIncludes 10 DLB patients from Rowe et al.3012 PDD10 PD41 HCMulticenter study (UK, Finland, Australia).MRI11C-PIB PET60-90 min 11C-PIB uptake ratio; ROI v. cerebellum.Voxel-based comparison with threshold p PDD/PD/HC.PiB binding in DLB comparable to AD.In LBD (DLB+PDD) relative striatal binding was associated with improved performance on UPDRS.Johansson et al. 200836Johansson A. Savitcheva I. Forsberg A. et al.[(11)C]-PIB imaging in patients with Parkinson's disease: preliminary results.Parkinsonism Relat Disord. 2008; 14: 345-347Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar5 PD16 AD6 HCAD and HC from previous study.PD: not stated.11C-PIB PET11C-L-DOPA PET40–60 min regional uptake volume of interest v. cerebellum.5 cortical areas, subcortical white matter, pons, striatum.PiB retention was greater in AD than PD in all cortical areas and striatum. Lower in PD than control in frontal, parietal and cingulate areas.Maetzler et al. 200831Maetzler W. Reimold M. Liepelt I. et al.[11C]PIB binding in Parkinson's disease dementia.Neuroimage. 2008; 39: 1027-1033Crossref PubMed Scopus (123) Google Scholar10 PDD6 AD11 HCNot stated.11C-PIB PET42–72 min ROI SUVR v. cerebellum.Frontal cortex, posterior cingulate, striatum, thalamus, brainstem, cerebellum, white matter2/10 PDD had "AD-like" pattern of amyloid deposition.Brainstem:posteriorcingulate DVR: PDD>control, AD, "AD-like" PD.Maetzler et al. 200933Maetzler W. Liepelt I. Reimold M. et al.Cortical PIB binding in Lewy body disease is associated with Alzheimer-like characteristics.Neurobiol Dis. 2009; 34: 107-112Crossref PubMed Scopus (148) Google Scholar9 DLB12 PDD14 PDWard/OP dept. in neurodegenerative dept. of a university hospital.11C-PIB PET42–72 min ROI SUVR v. cerebellum.5 cortical areas, whole cortex, striatum.PiB positive patients had lower CSF Aβ42, higher ApoE4 allele rate, all had dementia. Within dementia, PiB positive had lower MMSE scores.Jokinen et al. 201035Jokinen P. Scheinin N. Aalto S. et al.[(11)C]PIB-, [(18)F]FDG-PET and MRI imaging in patients with Parkinson's disease with and without dementia.Parkinsonism Relat Disord. 2010; 16: 666-670Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar11 PDD8 PD24 HCUniversity hospital.11C-PIB PET18F-FDG PETMRI60–90 min 11C-PIB uptakeROI v. cerebellum.5 cortical areas, caudate, putamen.No significant difference between groups in any cortical area. PDD more likely to show 1+ cortical areas with increased PiB uptake.Foster et al. 201027Foster E.R. Campbell M.C. Burack M.A. et al.Amyloid imaging of Lewy body-associated disorders.Mov Disord. 2010; 25: 2516-2523Crossref PubMed Scopus (120) Google Scholar6 DLB15 PDD9 PD-MCI8 PD9 HCMovement disorders center.11C-PIB PETMRI60 min dynamic scan. Binding potentials of ROIs and MCBP. Logan graphical analysis, cerebellum as reference.5 cortical areas, caudate, mean cortex.No differences in MCBP or regional BPs between groups.Correlation between caudate BP/MCBP and MMSE in some groups.Burke et al. 201142Burke J.F. Albin R.L. Koeppe R.A. et al.Assessment of mild dementia with amyloid and dopamine terminal positron emission tomography.Brain. 2011; 134: 1647-1657Crossref PubMed Scopus (43) Google Scholar14 DLB36 AD25 FTDCognitive disorders clinic.11C-PIB PET11C-DTBZ PET80 min scan. ROI DVR v. cerebellum. Subjective visual assessment.Frontal cortex : white matter DVR ratio.Only moderate concordance between clinical diagnosis and diagnosis based on scan results.Claasen et al. 201129Claassen D.O. Lowe V.J. Peller P.J. et al.Amyloid and glucose imaging in dementia with Lewy bodies and multiple systems atrophy.Parkinsonism Relat Disord. 2011; 17: 160-165Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar3 DLB3 MSA12 HCNeurology clinic.11C-PIB PET18F-FDG PETMRI40–60 min acquisition. ROI v. cerebellum.7 cortical areas and caudate.Higher binding found in DLB in all areas. Most marked in prefrontal, parietal, temporal, and precuneus.Villemagne et al. 201128Villemagne V.L. Ong K. Mulligan R.S. et al.Amyloid Imaging with F-18-Florbetaben in Alzheimer Disease and Other Dementias.J Nucl Med. 2011; 52: 1210-1217Crossref PubMed Scopus (278) Google Scholar7 DLB5 PD30 AD20 MCI11 FTD4 VaD32 HCMemory disorders service, movement disorders clinics.18F-Florbetaben PETMRI90–110 min acquisition.ROI SUVR v. cerebellar cortex9 cortical areas, total cortex, 6 non-cortical areas.AD and MCI had higher neocortical and striatal binding than controls. No other significant differences between groups.Gomperts et al. 201225Gomperts S.N. Locascio J.J. Marquie M. et al.Brain amyloid and cognition in Lewy body diseases.Mov Disord. 2012; 27: 965-973Crossref PubMed Scopus (134) Google Scholar18 DLB12 PDD14 PD-MCI29 PD85 HCMovement disorders and memory disorders units. HCS from separate study.11C-PIB PET60 min dynamic acquisition. Logan graphical analysis method. ROI DVR v. cerebellum.SPM analysis corrected for multiple comparisons (false discovery rate).PrecuneusVoxel-wise comparison.DLB exhibited higher binding than other groups, particularly in frontal and parietal areas. No differences found between non-DLB groups.PiB burden increased in ApoE4 genotype across entire cohort.In DLB increased PiB binding was associated with decreased MMSE score and poorer semantic memory.Graff-Radford et al. 201238Graff-Radford J. Boeve B.F. Pedraza O. et al.Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies.Brain. 2012; 135: 2470-2477Crossref PubMed Scopus (52) Google Scholar7 DLB (of 54 DLB)AD research center (retrospective study of pts. involved in longitudinal study).11C-PIB PETMRI40–60 min. ROI v. cerebellum.Partial volume correction.Global cortical retention.Both subjects who declined were PiB positive; all 3 subjects who improved were PiB negative.Kantarci et al. 201226Kantarci K. Lowe V.J. Boeve B.F. et al.Multimodality imaging characteristics of dementia with Lewy bodies.Neurobiol Aging. 2012; 33: 2091-2105Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar21 DLB21 AD42 HCDLB recruited from AD research centre. AD and HC from a longitudinal cohort.11C-PIB PET18F-FDG PETMRI40–60 min acquisition.ROI v. cerebellum.Voxel based comparison using FWE correction. Partial volume correction.Global cortical retention.Voxel-wise comparison.DLB PiB binding was significantly lower than AD but significantly higher than controls.No relationship found between global PiB and motor impairment, dementia rating, visual hallucinations or duration of symptoms.Petrou et al. 201232Petrou M. Bohnen N.I. Muller M.L. et al.Abeta-amyloid deposition in patients with Parkinson disease at risk for development of dementia.Neurology. 2012; 79: 1161-1167Crossref PubMed Scopus (79) Google Scholar40 PD at risk for dementiaUniversity-based movement disorders subspecialty clinic.11C-PIB PET11C-DTBZ PETMRI80 min acquisition. Logan graphical analysis method.DVR v. cerebellum.Mean cortical PiB DVR.Visual assessment.Cortical PiB was inversely correlated with overall cognitive score and WAIS score.Ossenkoppele et al. 201343Ossenkoppele R, Prins ND, Pijnenburg YA, et al: Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement 2013; 9:414–421Google Scholar66 AD30 MCI15 SMC18 FTD5 DLB20 otherSpecialist memory disorder clinic. Patients mostly attending for second/third opinion.11C-PIB PET18F-FDG PETMRI90 min dynamic scan. ROI BP v. cerebellum.For 12 patients 60–90 min SUVR ROI v. cerebellum.Visual assessment.11C-PIB PET contributed to diagnostic process in 86% of patients, mainly used to rule out AD.Shimada et al. 201334Shimada H, Shinotoh H, Hirano S, et al: Beta-amyloid in Lewy body disease is related to Alzheimer's disease-like atrophy. Mov Disord 2013; 28:169–175Google Scholar8 DLB7 PDD13 AD22 HCNot stated.11C-PIB PETMRI90 min dynamic scan. Logan graphical analysis method.VOI DVR v. cerebellum.Mean cortical PiB DVR.4 cortical areas.PiB positive LBD subjects demonstrated cortical atrophy compared with HC; greater atrophy in parahippocampal regions than PiB negative LBD subjects.Gomperts et al. 201337Gomperts S.N. Locascio J.J. Rentz D. et al.Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia.Neurology. 2013; 80: 85-91Crossref PubMed Scopus (128) Google Scholar35 PD11 PD-MCINot stated.11C-PIB PET60 min dynamic scan. Logan graphical analysis method. DVR v. cerebellum.Precuneus, frontal cortex, and striatum.Higher PiB retention at baseline associated with progression to MCI or dementia and with deterioration in executive function.Motor deterioration not linked to baseline striatal or precuneus amyloid burden.Notes: DLB: dementia with Lewy bodies; PD(D): Parkinson disease (dementia); LBD: Lewy body dementias (DLB/PDD); AD: Alzheimer disease; MSA: multisystem atrophy; FTD: frontotemporal dementia; VaD: vascular dementia; MCI: mild cognitive impairment; HC: healthy controls; SMC: subjective memory complaint; PET: positron emission tomography; MRI: magnetic resonance imaging; PiB: Pittsburgh compound B; DTBZ: dihydrotetrabenazine; FDG: fluorodeoxyglucose; ROI: region of interest; SUVR: standardised uptake value ratio; MCBP: mean cortical binding potential; DVR: distribution volume ratio; SPM: statistical parametric mapping; FWE: family-wise error.a Includes 10 DLB patients from Rowe et al.30Rowe C.C. Ng S. Ackermann U. et al.Imaging beta-amyloid burden in aging and dementia.Neurology. 2007; 68: 1718-1725Crossref PubMed Scopus (910) Google Scholar Open table in a new tab ResultsDementia with Lewy BodiesWhen compared with healthy controls, four studies found DLB to be associated with significantly greater cortical and subcortical 11C-PiB binding on PET imaging.23Edison P. Rowe C.C. Rinne J.O. et al.Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography.J Neurol Neurosurg Psychiatry. 2008; 79: 1331-1338Crossref PubMed Scopus (347) Google Scholar, 24Gomperts S.N. Rentz D.M. Moran E. et al.Imaging amyloid deposition in Lewy body diseases.Neurology. 2008; 71: 903-910Crossref PubMed Scopus (378) Google Scholar, 25Gomperts S.N. Locascio J.J. Marquie M. et al.Brain amyloid and cognition in Lewy body diseases.Mov Disord. 2012; 27: 965-973Crossref PubMed Scopus (134) Google Scholar, 26Kantarci K. Lowe V.J. Boeve B.F. et al.Multimodality imaging characteristics of dementia with Lewy bodies.Neurobiol Aging. 2012; 33: 2091-2105Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar A 32% greater uptake was found in one study,23Edison P. Rowe C.C. Rinne J.O. et al.Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography.J Neurol Neurosurg Psychiatry. 2008; 79: 1331-1338Crossref PubMed Scopus (347) Google Scholar although six controls with raised 11C-PiB binding had been excluded from analysis, as the aim of the study was to examine patterns of raised Aβ deposition in LB disorders.Two studies failed to find a significant difference between DLB and controls in global or regional Aβ ligand binding.27Foster E.R. Campbell M.C. Burack M.A. et al.Amyloid imaging of Lewy body-associated disorders.Mov Disord. 2010; 25: 2516-2523Crossref PubMed Scopus (120) Google Scholar, 28Villemagne V.L. Ong K. Mulligan R.S. et al.Amyloid Imaging with F-18-Florbetaben in Alzheimer Disease and Other Dementias.J Nucl Med. 2011; 52: 1210-1217Crossref PubMed Scopus (278) Google Scholar In both, DLB displayed greater binding (mean cortical binding potential: 0.18 versus 0.0827Foster E.R. Campbell M.C. Burack M.A. et al.Amyloid imaging of Lewy body-associated disorders.Mov Disord. 2010; 25: 2516-2523Crossref PubMed Scopus (120) Google Scholar; neocortex standardized uptake value ratio: 1.38 versus 1.2628Villemagne V.L. Ong K. Mulligan R.S. et al.Amyloid Imaging with F-18-Florbetaben in Alzheimer Disease and Other Dementias.J Nucl Med. 2011; 52: 1210-1217Crossref PubMed Scopus (278) Google Scholar). It should be noted that these studies contained smaller DLB samples (N = 6 and N = 7, respectively) than those that found significant differences (N = 8–2123Edison P. Rowe C.C. Rinne J.O. et al.Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography.J Neurol Neurosurg Psychiatry. 2008; 79: 1331-1338Crossref PubMed Scopus (347) Google Scholar, 24Gomperts S.N. Rentz D.M. Moran E. et al.Imaging amyloid deposition in Lewy body diseases.Neurology. 2008; 71: 903-910Crossref PubMed Scopus (378) Google Scholar, 25Gomperts S.N. Locascio J.J. Marquie M. et al.Brain amyloid and cognition in Lewy body diseases.Mov Disord. 2012; 27: 965-973Crossref PubMed Scopus (134) Google Scholar, 26Kantarci K. Lowe V.J. Boeve B.F. et al.Multimodality imaging characteristics of dementia with Lewy bodies.Neurobiol Aging. 2012; 33: 2091-2105Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar).Particular areas of increased Aβ ligand binding have included frontal, parietal, and cingulate areas, along with the striatum,24Gomperts S.N. Rentz D.M. Moran E. et al.Imaging amyloid deposition in Lewy body diseases.Neurology. 2008; 71: 903-910Crossref PubMed Scopus (378) Google Scholar, 25Gomperts S.N. Locascio J.J. Marquie M. et al.Brain amyloid and cognition in Lewy body diseases.Mov Disord. 2012; 27: 965-973Crossref PubMed Scopus (134) Google Scholar, 26Kantarci K. Lowe V.J. Boeve B.F. et al.Multimodality imaging characteristics of dementia with Lewy bodies.Neurobiol Aging. 2012; 33: 2091-2105Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar, 29Claassen D.O. Lowe V.J. Peller P.J. et al.Amyloid and glucose imaging in dementia with Lewy bodies and multiple systems atrophy.Parkinsonism Relat Disord. 2011; 17: 160-165Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 30Rowe C.C. Ng S. Ackermann U. et al.Imaging beta-amyloid burden in aging and dementia.Neurology. 2007; 68: 1718-1725Crossref PubMed Scopus (910) Google Scholar with relative sparing of the medial temporal lobe.24Gomperts S.N. Rentz D.M. Moran E. et al.Imaging amyloid deposition in Lewy body diseases.Neurology. 2008; 71: 903-910Crossref PubMed Scopus (378) Google Scholar, 26Kantarci K. Lowe V.J. Boeve B.F. et al.Multimodality imaging characteristics of dementia with Lewy bodies.Neurobiol Aging. 2012; 33: 2091-2105Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar, 30Rowe C.C. Ng S. Ackermann U. et al.Imaging beta-amyloid burden in aging and dementia.Neurology. 2007; 68: 1718-1725Crossref PubMed Scopus (910) Google ScholarFour studies have compared amyloid brain imaging in DLB and AD. The largest study (N = 42) found global 11C-PiB retentio
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