Introduction
Imaging modality | Application | Main findings |
---|---|---|
FP-CIT SPECT | Differentiating from AD and HC | Decreased dopamine transporter uptake in the basal ganglia |
FDG-PET | Supportive of diagnosis | Reduced glucose metabolism in occipital lobes |
CT | Excluding secondary causes of dementia | Intact brain structure |
MRI | Differentiating from AD | Relative preservation of medial temporal lobe structures |
MIBG | Differentiating from AD | Low uptake |
Diagnosis of DLB
Structural imaging
Study | MR measurement | Assessment | Groups | Findings in DLB patients |
---|---|---|---|---|
Ballard et al. [59] | Visual inspection of white matter lesions on T2-weighted MR images | Hyperintensities | 17 DLB, 13 AD | Blood pressure drop > 30 mm Hg was associated with the severity of hyperintensities in the deep white matter and basal ganglia |
Barber et al. [55] | Cortical thickness | Atrophy | 27 DLB, 25 AD, 24 VaD, 26 HC | DLB patients had larger temporal lobe, amygdala and hippocampal volumes compared to AD, with no volumetric difference compared to VaD. Compared to HC, DLB exhibited relative preservation of whole brain volume |
Barber et al. [55] | Ventricular volumes and white matter lesions | White matter hyperintensities | 27 DLB, 25 AD | Periventricular hyperintensities correlated with increasing age and ventricular dilation in all subjects. Deep matter hyperintensities were associated with hypertension history |
Ballmaier et al. [19] | Cortical thickness | Atrophy | 16 DLB, 29 AD, 38 HC | DLB exhibited significantly less gray matter deficits bilaterally in the temporal lobe compared to AD |
Burton et al. [14] | Voxel-based morphometry | Atrophy | 25 DLB, 30 AD, 25 HC | Loss of gray matter volume bilaterally in the temporal and frontal lobes and insular cortex in patients with DLB compared to HC. Preservation of the medial temporal lobe, hippocampus and amygdala in DLB compared to AD |
Burton et al. [30] | Voxel-based morphometry | Atrophy | 17 DLB, 26 PDD, 31 PD, 28 AD, 36 HC | PDD exhibited bilateral loss of gray matter in the occipital lobe compared to PD. AD exhibited temporal lobe atrophy, including parahippocampal gyrus and hippocampus, compared to PDD. No differences found between PDD and DLB |
Burton et al. [56] | Automated technique using FLAIR image | White matter volume | 14 DLB, 13 PDD, 23 AD, 33 HC | AD exhibited increased white matter volume compared to HC. No differences were found in white matter volume in DLB compared to HC, AD or PDD |
Sauer et al. [40] | Task-based fMRI | BOLD signal | 9 DLB, 10 AD, 13 HC | DLB had increased activation in the superior temporal sulcus compared to AD during the motion task |
Beyer et al. [31] | Voxel-based morphometry | Atrophy | 18 DLB, 15 PDD, 21 AD, 20 HC | DLB exhibited increased cortical atrophy within the temporal, parietal and occipital lobes compared to PDD. AD exhibited greater atrophy within the temporal and frontal lobe compared to DLB |
Whitwell et al. [25] | Voxel-based morphometry & ROI-based analysis | Atrophy | 72 DLB, 72 AD, 72 HC | DLB exhibited preservation of the medial temporal lobe, inferior temporal regions as well as hippocampus and temporoparietal cortex compared to AD. Both AD and DLB demonstrated a loss of gray matter in the substantia innominata, though DLB exhibited a greater loss within the midbrain compared to AD |
Sanchez-Castaneda et al. [33] | Voxel-based morphometry | Atrophy | 12 DLB, 16 PDD, 16 HC | DLB demonstrated increased gray matter atrophy in the right inferior frontal lobe, the right superior frontal gyrus and the right premotor area compared to PDD. Within the DLB group, reduced anterior cingulate and prefrontal volume correlated with worse performance on the Continuous Performance Test, whilst right hippocampal and amygdala volume correlated with Visual Memory Test |
Lee et al. [32] | Voxel-based morphometry | Atrophy | 18 DLB, 20 PDD | DLB exhibited greater gray matter atrophy in the left occipital, parietal and striatal areas compared to PDD, as well as a greater reduction in white matter density within the occipital and left occipito-parietal areas |
Sanchez-Castaneda et al. [34] | Voxel-based morphometry | Atrophy | 12 DLB, 15 PDD | DLB with hallucinations exhibited greater loss of gray matter in the right inferior frontal gyrus compared to DLB without hallucinations. Compared to PDD with hallucinations, DLB with hallucinations had a greater reduction of gray matter in the bilateral premotor area, as well as reduced volume in the left precuneus and inferior frontal lobe correlating with visual hallucination |
Hippocampal radial distance technique | Hippocampal atrophy | 16 DLB, 55 AD, 42 HC | DLB demonstrated atrophy predominately within the left CA1 region and subiculum compared to HC | |
Hayashi et al. [23] | Voxel-based morphometry | Atrophy | 60 DLB, 210 AD | DLB exhibited less atrophy in the entorhinal cortex compared to AD |
Taylor et al. [41] | Task-based fMRI | BOLD signal | 17 DLB, 19 HC | DLB showed reduced functional activation in visual area V5/MT (middle temporal) in response to motion stimuli |
Watson et al. [22] | Voxel-based morphometry | Atrophy | 35 DLB, 36 AD, 35 HC | Although DLB exhibited gray matter atrophy in occipital, parietal, temporal and subcortical structures when compared to HC, this was to a lesser extent than AD. DLB appeared to have a relative preservation of the medial temporal lobe compared to AD |
Watson et al. [22] | Diffusion tensor imaging | White matter integrity | 35 DLB, 36 AD, 35 HC | In DLB, reduced FA was identified in parieto-occipital white matter tracts when compared to HC. However, when DLB were compared to AD, reduced FA was observed in the pons and left thalamus. Impaired episodic memory, was associated with increased MD, whilst letter fluency and motor parkinsonism severity were associated with reduced FA |
Franciotti et al. [36] | rs-fMRI: ICA | Functional connectivity | 18 DLB, 18 AD, 15 HC | DLB had reduced FC in the right hemisphere compared to HC, but not AD, which was found to correlate with severity of fluctuations |
Fukui et al. [58] | Visual inspection of T2*-weighted MR images | Cerebral microbleeds quantification | 59 DLB, 81 AD | DLB exhibited increased microbleeds in all brain areas, apart from occipital lobe, compared to AD. The number of microbleeds was positively correlated with the severity of white matter lesions in both DLB and AD |
Kenny et al. [38] | rs-fMRI: seed-based | Functional connectivity | 15 DLB, 16 AD, 16 HC | DLB and AD exhibited increased thalamic and caudate FC compared to HC. DLB patients showed greater putaminal connectivity compared to AD and HC |
Lebedev et al. [18] | Cortical thickness | Atrophy | 97 DLB, 97 AD | DLB and AD were differentiated with a sensitivity of 82.1% and specificity of 85.7%. Cortical thinning, in DLB, was localized to the middle and posterior cingulate, lateral orbito-frontal and superior temporo-occipital regions |
Mak et al. [50] | Cortical thickness and subcortical volumes | Atrophy | 13 DLB, 23 AD, 33 HC | AD exhibited greater hippocampal atrophy compared to DLB. In DLB, cortical thinning in the frontal and parietal regions correlated with a decline in global cognition and motor deterioration |
Peraza et al. [49] | rs-fMRI | Functional connectivity | 18 DLB, 12 PDD, 17 HC | When compared to HC, DLB had greater FC alterations than PDD for seeds situated within the fronto-parietal network. No differences were found when DLB and PDD were compared directly |
Watson et al. [17] | Cortical thickness | Atrophy | 31 DLB, 30 AD, 33 HC | In DLB, cortical atrophy was less diffuse compared to AD, though cortical change was found to predominately affect posterior structures (inferior parietal, fusiform gyrus and posterior cingulate). In DLB, the average reduction medial temporal lobe cortical thickness was less (6–10%) compared to AD (15–24%) |
Delli Pizzi et al. [24] | Cortical thickness and subcortical volumes | Atrophy | 19 DLB, 15 AD, 19 HC | The cornu ammonis and subiculum were bilaterally preserved in DLB compared to AD. The perirhinal cortex and parahippocampus were damaged in DLB, but preserved in AD |
Watson et al. [53] | Cortical thickness and subcortical volumes | Atrophy | 33 DLB, 32 AD, 35 HC | DLB exhibited volumetric loss in the bilateral putamen, left thalamus and total subcortical gray measures compared to controls. AD exhibited a more pronounced loss of gray matter volume in the left pallidum, right thalamus and bilateral amygdala and hippocampus compared to DLB |
Shams et al. [27] | SWI analysis | Iron | 19 DLB, 20 AD, 20 FTD, 17 MCI, 21 HC | An abnormal swallow tail sign was most common in DLB, with a predictive value only in DLB |
Comparison between DLB and AD
Comparison between DLB and PDD
Functional imaging
Comparison between DLB and AD
Comparison between DLB and PDD
Cortical and subcortical involvement in DLB
Cerebrovascular pathology
Sensitivity and specificity of structural imaging modalities in pathologically proven DLB cases
Molecular imaging
Study | Target | Radioligand | Groups | Findings in DLB patients |
---|---|---|---|---|
Rowe et al. [100] | Amyloid | [11C]PIB | 10 DLB, 17 AD, 6 FTD, 9 MCI, 27 HC | Cortical PIB binding was markedly elevated in every AD subject. In DLB, binding was lower, more variable and correlated inversely with the interval from onset of cognitive impairment to diagnosis |
Edison et al. [67] | Amyloid | [11C]PIB | 13 DLB, 12 PDD, 10 PD, 41 HC | Increase in mean brain uptake |
Gomperts et al. [94] | Amyloid | [11C]PIB | 8 DLB, 7 PDD, 11 PD, 15 AD, 37 HC | Global cortical amyloid burden was higher in DLB than PDD/PD and comparable to AD |
Maetzler et al. [98] | Amyloid | [11C]PIB | 9 DLB, 12 PDD, 14 PD | [11C]PIB binding was decreased in all PD (non-demented) [11C]PIB binding was increased in 4 PDD and 4 DLB Increased [11C]PIB binding was associated with MMSE scores, ApoE4, age, and onset of parkinsonism and dementia |
Foster et al. (2010) | Amyloid | [11C]PIB | 6 DLB, 9 HC, 8 PD-noCI, 9 PD-MCI, 15 PDD | Regional [11C]PIB binding potentials were not significantly different across participant groups. Elevated binding was associated with worse global cognitive impairment in participants with Lewy body disorders but was not associated with any other clinical or neuropsychological features |
Shimada et al. (2012) | Amyloid | [11C]PIB | 8 DLB, 7 PDD, 13 AD,17 HC | Amyloid deposition was associated with AD-like atrophy in DLB/PDD patients |
Ikonomovic et al. (2012) | Amyloid | [11C]PIB | 1 Probable DLB and possible AD, 1 Probable AD | [11C]PIB was negative in probable DLB, with scarce amyloid plaques identified in less than 2% of the cortical area at autopsy [11C]PIB was positive in probable AD with plaques in up to 12% of the cortical area |
Gomperts et al. [97] | Amyloid | [11C]PIB | 18 DLB, 29 PD-noCI, 14 PD-MCI, 12 PDD,85 HC | [11C]PIB uptake was higher in DLB than in any of the other groups No differences in [11C]PIB uptake across PDD, PD-MCI, PD and HC [11C]PIB increased with age and ApoE4 in all patient groups |
Sarro et al. [95] | Amyloid | [11C]PIB | 20 DLB | Higher binding at baseline was predictive of faster cortical, striatal degeneration |
Villemagne et al. (2011) | Amyloid | [18F]Florbetaben | 7 DLB, 20 MCI, 30 AD, 11 FTLD, 5 PD, 4 VaD,32 HC | [18F]Florbetaben was positive in 29% of DLB. Cortical binding distribution was similar to AD, however cortical uptake was lower than in AD [18F]Florbetaben was negative in all PD |
Claassen et al. (2011) | Amyloid, Glucose metabolism | [11C]PIB [18F]FDG | 3 DLB, 3 MSA, 12 HC | All DLB had increased [11C]PIB uptake. No [11C]-PIB uptake in MSA In DLB, there was correspondence between areas with hypometabolism and high [11C]PIB uptake |
Iannaccone et al. (2013) | TSPO | [11C]PK11195 | 6 DLB, 11 HC | Increased microglia activation in caudate, putamen, thalamus, substantia nigra, cortex and cerebellum |
Albin et al. (1996) | Glucose metabolism | [18F]FDG | 6 DLB | FDG-PET revealed diffuse cerebral hypometabolism in both pure DLBD and DLBD-AD, with marked declines in association cortices and relative sparing of subcortical structures and primary somatomotor cortex. These subjects also had hypometabolism in the occipital association cortex and primary visual cortex |
Imamura et al. (1997) | Glucose metabolism | [18F]FDG | 19 DLB, 19 AD | In DLB patients, when compared with AD patients, significant glucose hypometabolism was distributed in the temporo-parieto-occipital association cortices and the cerebellar hemispheres. In contrast, glucose metabolism in the medial temporal and cingulate was significantly lower in AD patients |
Ishi et al. (1998) | Glucose metabolism | [18F]FDG | 12 DLB, 12 AD, 12 HC | Glucose metabolism was significantly lower in patients with DLB than HCs in most parts of the brain, except the sensorimotor cortices, basal ganglia, thalamus, and pons. Between the DLB and AD groups, there were significant regional differences in glucose metabolism in the medial and lateral occipital lobes. Occipital glucose metabolism was a useful measure for the differential diagnosis of DLB from AD. The sensitivity and the specificity were 92% when using the minimal value of the normalized occipital metabolism in the HC group as the cutoff point |
Higuchi et al. [119] | Glucose metabolism | [18F]FDG | 6 probable DLB, 1 DLB, 11 probable AD, 10 HC | Among widespread cortical regions, glucose hypometabolism was evident in the DLB group. The metabolic reduction was most pronounced in the visual association cortex compared to that in the AD group. Using a metabolic ratio of 0.92 in the visual association cortex as a cutoff, DLB could be distinguished from AD with a sensitivity of 86% and a specificity of 91% |
Liu et al. [71] | Glucose metabolism, amyloid | [18F]FDG, [11C]PIB | 37 DLB, 5 HC | DLB subjects exhibited cortical amyloid deposition and hypometabolism in the bilateral temporo-parieto-occipital region, insula, precuneus, posterior cingulate, frontal lobe and caudate nuclei |
Gomperts et al. [102] | Tau, amyloid | [18F]AV1451, [11C]PIB | 7 DLB, 8 PD-impaired, 9 PD-normal, 29 HC | In patients with DLB, cortical [18F]AV1451uptake was highly variable and greater than in the HC, particularly in the inferior temporal gyrus and precuneus. Elevated cortical [18F]AV1451 binding was observed in 4 of 17 patients with Lewy body disease with low cortical [11C]PIB retention. For DLB and PD-impaired patients, greater [18F]AV1451 uptake in the inferior temporal gyrus and precuneus was associated with increased cognitive impairment as measured with the MMSE and the CDR |
Shimada et al. (2015) | AChE | [11C]MP4A | 14 DLB, 25 AD, 18 HC | Mean cortical cholinergic activity in AD patients (8.2%) compared with normal subjects and DLB patients (27.8%) was lower than HC. There was a significant difference in mean cortical cholinergic activity between AD and DLB patients |
Gilman et al. (2004) | VMAT2 | [11C]DTBZ | 20 DLB [Six developed parkinsonism at least 1 year before dementia (DLB/PD) and 14 developed dementia before parkinsonism or at about the same time (DLB/AD)], 25 AD, 19 NC | Striatal mean binding potential was decreased by 62%–77% in the DLB/PD group and 45%–67% in the DLB/AD compared to AD and control. Binding was lower in the DLB/PD group than the DLB/AD. Both DLB groups had an anterior to posterior binding deficit gradient relative to controls, largest in posterior putamen, smaller in anterior putamen, smallest in caudate nucleus. PET with (+)-[11C]DTBZ differentiates DLB from AD, and decreased binding in AD may indicate subclinical DLB pathology |
Koeppe et al. (2008) | VMAT2 | [11C]DTBZ | 25 DLB, 30 PD, 25 AD, 57 NC | [11C]DTBZ distribution volume was decreased significantly in caudate nucleus, anterior putamen, and posterior putamen in DLB and PD compared with AD and NC. The gradient was significantly steeper in PD than DLB. Both PD and DLB showed significantly greater interhemispheric striatal binding asymmetry than NC. PD had greater asymmetry than DLB. Greater reduction of K1 occurred in occipital cortex in DLB than AD. DLB was distinguished from AD more effectively on the basis of striatal distribution volume than occipital K1. DLB was distinguished from PD more effectively on the basis of cerebral cortical K1 than striatal distribution patterns |
Metabolic imaging
Imaging dopaminergic dysfunction
Imaging cardiac sympathetic innervation
Amyloid imaging
Tau imaging
Alpha-synuclein imaging
Sensitivity and specificity of molecular imaging modalities in pathologically proven DLB cases
[123I]-FP-CIT-SPECT
Study | Imaging modality | Groups (based on clinical diagnosis) | Population | Interval between imaging and death (years) | Sensitivity (imaging vs postmortem) | Specificity (imaging vs postmortem) | Sensitivity (clinical diagnosis vs postmortem) | Specificity (clinical diagnosis vs postmortem) | Sensitivity (DLB vs AD) | Specificity (DLB vs AD) | Comments |
---|---|---|---|---|---|---|---|---|---|---|---|
Higuchi et al. [119] | [18F]FDG | 7 DLB 11 AD, 10 NC | Miyagi Parkinson’s Disease Patient Registry | NA | NA | NA | NA | NA | 86% | 91% | A metabolic ratio of 0.92 in the visual association cortex was applied as a cutoff value (mean-2 SD) to discriminate DLB from AD |
Minoshima et al. [120] | [18F]FDG | 11 DLB (7 LBVAD, DLBD) 10 autopsy-confirmed-AD, 53 clinically diagnosed probable AD | Michigan Alzheimer’s Disease Re-search Center | 3.4 ± 2.6 | NA | NA | NA | NA | 90% | 80% | Only DLB patients harbored significant metabolic reductions in the occipital cortex, specifically in the primary visual cortex |
Walker et al. [76] | [123I]FP-CIT-SPECT | 13 DLB, 6 AD, 1 CBD, 16 HC | West-Essex Cohort | 2.8 ± 1.8 | 88% | 100% | 75% | 42% | NA | NA | The authors explored whether [123I]FP-CIT imaging improved the accuracy in discriminating dementia with Lewy bodies from non-dementia with Lewy bodies comparing clinical criteria with autopsy findings |
Burton et al. [16] | Structural MRI | 23 DLB, 11 AD, 12 VCI | Institute for Ageing and Health, Newcastle University | NA | NA | NA | NA | NA | 91% | 94% | The medial temporal lobe atrophy was found to serve as a diagnostic marker with high accuracy in differentiating AD from DLB and VCI |
Lim et al. [66] | [18F]FDG | 14 DLB (4 autopsy-confirmed), 10 AD (1 autopsy-confirmed) | Austin Health Memory Disorders and Neurobehavioural Disorder Clinics | NA | NA | NA | NA | NA | 62% − 86% | 100% | The cingulate island sign had the highest specificity, as opposed to hypometabolism in the lateral occipital cortex (88%) |
Colloby et al. (2012) | [123I]FP-CIT-SPECT | 7 DLB 12 PDD 4 AD | Community-dwelling referred to Old Age Psychiatry services | 3.5 ± 1.7 | NA | NA | NA | NA | NA | NA | It was shown that nigral dopaminergic cell loss (and not α-synuclein, tau or amyloid-β pathology) was associated with lower striatal [123I]FP-CIT uptake |
Harper et al. [61] | Structural MRI | 28 DLB, 101 AD, 55 FTLD, 55 HC | Queen Square Brain Bank, London; King’s College Hospital, London; VU Medical Centre, Amsterdam; Institute for Ageing and Health, Newcastle | NA | NA | NA | NA | NA | 64% | 82% | SVC classification accuracy demonstrated to be equivalent to or better than expert diagnosis, using six visual rating scales: medial temporal, posterior, anterior temporal, orbito-frontal, anterior cingulate and fronto-insula) |
Thomas et al. [112] | [123I]FP-CIT-SPECT | 33 DLB 22 AD | Newcastle Brain Tissue Resource Cohort | 3.3 ± 2.3 | 80% | 92% | 87% | 72% | NA | NA | Among patients with DLB, 10% (3 patients) met pathologic criteria for Lewy body disease but had normal [123I]FP-CIT imaging. While an abnormal [123I]FP-CIT scan supported Lewy body disease, an unremarkable scan did not exclude diagnosis especially when the brainstem was minimally involved. This study provided Class I evidence that [123I]FP-CIT scan accurately identifies patients with DLB |