Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD

OBJECTIVE: To compare regional cerebral blood flow (rCBF) changes using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT in subjects with dementia with Lewy bodies (DLB) and AD and in normal age-matched control subjects; to examine the utility of SPECT changes in the differential diagnosis of AD and DLB. METHOD: Whole-brain SPECT scans were acquired using a single-headed rotating gamma camera (IGE CamStar XR/T) in elderly subjects with consensus criteria DLB (n = 23; mean age = 79.4 years), National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association AD (n = 50; 81.9 years), and normal control subjects (n = 20; 78.1 years) after injection with 500 MBq of 99mTc-HMPAO. Region-of-interest analysis was performed using a SPECT template registered in Talairach space, with rCBF normalized to cerebellum. RESULTS: Both DLB and AD subjects had significantly reduced rCBF in parietal and temporal regions compared with the control subjects. The AD group also showed a significant reduction in rCBF in the frontal and medial temporal regions and the DLB in the occipital areas compared with control subjects. AD and DLB groups differed only in occipital perfusion (p < 0.01). SPECT measures (occipital and medial temporal) correctly classified 69% of all subjects, with a 65% sensitivity and 87% specificity for DLB against AD and control subjects. CONCLUSION: Temporoparietal hypoperfusion on SPECT is common to both AD and DLB. Occipital hypoperfusion is more frequently seen in DLB. Although not diagnostically specific in individual cases, occipital hypoperfusion on SPECT should raise suspicion that DLB may be the cause of dementia, prompting careful search for other features of the disorder.     

Differentiation of dementia with Lewy bodies from Alzheimer's disease using brain SPECT

We compared regional cerebral blood flow (CBF) patterns in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) using single photon emission computed tomography (SPECT) and investigated the diagnostic utility of SPECT study in differentiating between DLB and AD. SPECT data on 20 patients with DLB and 75 patients with AD were analyzed using three-dimensional stereotactic surface projections. Regional CBF reduction was determined by quantitative analysis using stereotactic extraction estimation method. The DLB group showed a significant CBF reduction in the temporoparietal, frontal lobe and posterior cingulate, similar to the CBF pattern in the AD group, but regional CBF in the medial and lateral occipital lobes decreased significantly in patients with DLB compared with patients with AD. Receiver operating characteristic analysis revealed that regional CBF measurement of the medial occipital lobe, including the cuneus and lingual gyrus, yielded a sensitivity of 85% and a specificity of 85% in discriminating DLB from AD. Objective and quantitative CBF measurement in the medial occipital lobe may be useful in the clinical differentiation of DLB and AD.     

Deep gray matter hyperperfusion with occipital hypoperfusion in dementia with Lewy bodies

Although decreased occipital perfusion is a characteristic feature of dementia with Lewy bodies (DLB), not all patients with DLB show a significant decreased perfusion in the occipital lobe. We explored characteristics of perfusion changes to improve the identification of DLB, in addition to occipital hypoperfusion. Statistical image analysis of single photon emission computed tomography data was performed on 22 patients with DLB and 25 patients with Alzheimer's disease (AD). A significant decreased perfusion in the occipital lobe was found in 16 patients with DLB (72%) and three patients with AD (12%), while a significant increased perfusion in the deep gray matter (striatum and/or thalamus) was found in 18 patients with DLB (81%) and eight patients with AD (31%), respectively. Either occipital hypoperfusion or deep gray matter hyperperfusion was found in 21 patients with DLB (95%), while in nine patients with AD (35%), indicating a sensitivity of 95% and a specificity of 65% in discriminating DLB from AD. Our results suggest that the addition of deep gray matter hyperperfusion to occipital hypoperfusion may be useful in the clinical differentiation of DLB and AD.     

Occipital glucose metabolism in dementia with lewy bodies with and without Parkinsonism: a study using positron emission tomography

Reduction of glucose metabolism in the occipital lobe is reported in dementia with Lewy bodies (DLB) and Parkinson's disease. If dysfunction of the nigrostriatal system is responsible for occipital hypometabolism, (1) DLB patients with parkinsonism would show a lower occipital metabolism than do patients without parkinsonism, and (2) DLB patients without parkinsonism would show an occipital metabolism comparable to those of normal subjects and patients with Alzheimer's disease (AD). To examine these hypotheses, we studied the regional cerebral metabolic rate of glucose (rCMRglc) in patients with a clinical diagnosis of DLB or AD, using (18)F-fluorodeoxyglucose and positron emission tomography. The subjects consisted of 15 DLB patients with parkinsonism, 7 DLB patients without parkinsonism and 7 AD patients without parkinsonism. The medial and lateral occipital rCMRglc was significantly lower in the DLB patients without parkinsonism than in the AD patients. There were no significant differences in occipital metabolic rates between the DLB groups with and without parkinsonism. DLB patients without parkinsonism showed a significant reduction of occipital glucose metabolism which is comparable with that of DLB patients with parkinsonism. The neurobiological bases of occipital hypometabolism in DLB may be pathological processes in the brainstem or basal forebrain structures other than the nigrostriatal system.     

Brain 3D-SSP SPECT analysis in dementia with Lewy bodies, Parkinson's disease with and without dementia, and Alzheimer's disease

OBJECTIVES: Cerebral blood flow was compared among patients with dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Parkinson's disease without dementia (PD), and Alzheimer's disease (AD) using three-dimensional stereotactic surface projection (3D-SSP) analysis. PURPOSE: We attempt to clarify the difference of reduction pattern on SPECT among patients having DLB, PDD, PD, AD. PATIENTS AND METHODS: Six patients with DLB, 7 patients with PDD who were matched with the DLB patients for age, unified Parkinson's disease rating scale-III (UPDRS-III) score, and degree of cognitive function disorders, 21 patients with PD who were matched with the DLB patients for age, UPDRS-III score, 12 patients with AD who were matched with the DLB patients for age and degree of cognitive function disorders, and 12 control subjects. All patients were examined by N-isopropyl-p[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT), and obtained images were analyzed with 3D-SSP using an image-analysis software, iSSP ver. 3.5. RESULTS: Although DLB and PDD showed similar cerebral perfusion reduction pattern at the lateral parietal association and lateral temporal association and precuneus on SPECT by the pixel-by-pixel comparison, greater perfusion reduction was observed in DLB than in PDD. Cerebral perfusion was decreased at the occipital lobe of the DLB patients compared with the AD patients. CONCLUSIONS: The regional pattern of blood flow reduction in the brain was found to be different among DLB, PD, and AD. Greater blood flow reduction was observed in DLB, although DLB and PDD showed similar reduction pattern. These regional differences were considered to suggest different and disease-specific combinations of underlying pathological and neurochemical processes.     

Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients treated with interferon-beta

To determine whether combined studies of Mini-Mental State Examination (MMSE) and brain single photon emission CT (SPECT) would provide more useful means of differentiating between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we studied 36 patients with probable DLB and 96 patients with probable AD. DLB patients had significantly better performance on word recall, but more impaired attention and copying than AD patients. We confirmed that a weighted score derived by Ala et al. [Ala, T.A., Hughes, L.F., Kyrouac, G.A., Ghobrial, M.W., Elble, R.J. The Mini-Mental State exam may help in the differentiation of dementia with Lewy bodies and Alzheimer' disease. Int J Geriatr Psychiatry 2002;17:503–9]: (Attention − 5/3 · Memory + 5 · Construction), was helpful in discriminating between DLB and AD. SPECT study revealed that medial occipital perfusion significantly decreased in DLB patients than AD patients. Combined studies of MMSE and brain SPECT achieved a high discrimination between DLB and AD with a sensitivity of 81% and a specificity of 85%, suggesting that there is a useful and practical approach to differentiate DLB from AD. Our findings will need to be substantiated in an independent and prospective study sample.     

Visual hallucinations and regional cerebral metabolism in dementia with Lewy bodies (DLB).

To investigate the neurobiological bases of visual hallucinations in dementia with Lewy bodies (DLB), regional cerebral glucose metabolism was compared among three patient groups; DLB with visual hallucinations, DLB without visual hallucinations and Alzheimer's disease (AD) without visual hallucinations. The regional metabolism was significantly lower in both DLB groups than in the AD group in the primary visual area and the posterior temporal, parietal and lateral occipital association areas. The hypometabolism in the right posterior temporal and parietal areas was significantly milder in DLB with visual hallucinations than in DLB without hallucinations. The hypometabolism in the primary visual cortex and the relatively preserved metabolism in the right temporoparietal association cortices may be associated with the occurrence of visual hallucinations in DLB patients.     

Association cortex hypoperfusion in mild dementia with Lewy bodies: a potential indicator of cholinergic dysfunction?

Dementia with Lewy bodies (DLB) is often associated with occipital hypometabolism or hypoperfusion, as well as deficits in cholinergic neurotransmission. In this study, 11 mild DLB, 16 mild AD and 16 age-matched controls underwent arterial spin-labeled perfusion MRI (ASL-pMRI) and neuropsychological testing. Patterns of cerebral blood flow (CBF) and cognitive performance were compared. In addition, combined ASL-pMRI and ChEI drug challenge (pharmacologic MRI) was tested as a probe of cholinergic function in 4 of the DLB participants. Frontal and parieto-occipital hypoperfusion was observed in both DLB and AD but was more pronounced in DLB. Following ChEI treatment, perfusion increased in temporal and parieto-occipital cortex, and cognitive performance improved on a verbal fluency task. If confirmed in a larger study, these results provide further evidence for brain cholinergic dysfunction in DLB pathophysiology, and use of pharmacologic MRI as an in vivo measure of cholinergic function.     

Usefulness of a blood flow analyzing program 3DSRT to detect occipital hypoperfusion in dementia with Lewy bodies

In the latest criteria for the clinical diagnosis of dementia with Lewy bodies (DLB), supportive features include generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity. In this study, we investigated the usefulness of a cerebral blood flow (CBF) quantification program '3DSRT' in detecting occipital hypoperfusion in DLB. Twenty two patients with probable DLB, 38 patients with probable Alzheimer's disease (AD) and 16 normal controls underwent brain perfusion SPECT. Compared with AD, DLB patients had a bilateral lower CBF in the posterior cerebral segments. The correlation of clinical symptoms and brain blood perfusion was examined by dividing the subjects into subgroups. DLB patients with Parkinsonism, when compared to non-Parkinsonism subgroup, had a lower CBF throughout the cerebrum with statistical significance in the posterior cerebral segments. The quantitative analysis of brain perfusion SPECT by 3DSRT could be a useful supportive measurement in the diagnosis of DLB.     

A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy bodies and Alzheimer's disease: magnetic resonance imaging volumetric study

OBJECTIVES: To compare medial and lateral temporal lobe atrophy on magnetic resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), and to examine the relationship between volumetric indices and cognitive and non-cognitive symptoms. METHODS: T(1)-weighted 1.0-tesla MRI scans were acquired in elderly subjects with DLB (n = 26; mean age = 75.8 years) and AD (n = 22; 77.3 years) and normal controls (n = 26; 76.2 years). MRI-based volume measurements of the hippocampus, parahippocampus, fusiform gyrus, combined inferior and middle temporal gyri, and superior temporal gyrus were acquired. RESULTS: Hippocampal and parahippocampal volumes were significantly larger in subjects with DLB compared to AD. Differences in hippocampal volumes between DLB and AD were observed across the entire length, and in all subjects with dementia there was a loss of hippocampal asymmetry compared to normal controls. Atrophy of temporal lobe structures correlated with memory impairment in both groups, and with age in DLB. There was no association between atrophy and psychotic symptoms in either group. CONCLUSIONS: Subjects with DLB and AD have a different pattern of temporal lobe atrophy with the most striking differences relating to medial rather than lateral temporal lobe structures. These structural differences could explain the relative preservation of memory function in DLB compared to AD.     

Alzheimer's disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation

Seeking antemortem markers to distinguish Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we examined brain glucose metabolism of DLB and AD. Eleven DLB patients (7 Lewy body variant of AD [LBVAD] and 4 pure diffuse Lewy body disease [DLBD]) who had antemortem position emission tomography imaging and autopsy confirmation were compared to 10 autopsy-confirmed pure AD patients. In addition, 53 patients with clinically-diagnosed probable AD, 13 of whom later fulfilled clinical diagnoses of DLB, were examined. Autopsy-confirmed AD and DLB patients showed significant metabolic reductions involving parietotemporal association, posterior cingulate, and frontal association cortices. Only DLB patients showed significant metabolic reductions in the occipital cortex, particularly in the primary visual cortex (LBVAD -23% and DLBD -29% vs AD -8%), which distinguished DLB versus AD with 90% sensitivity and 80% specificity. Multivariate analysis revealed that occipital metabolic changes in DLB were independent from those in the adjacent parietotemporal cortices. Analysis of clinically diagnosed probable AD patients showed a significantly higher frequency of primary visual metabolic reduction among patients who fulfilled later dinical criteria for DLB. In these patients, occipital hypometabolism preceded some clinical features of DLB. Occipital hypometabolism is a potential antemortem marker to distinguish DLB versus AD.     

Glucose hypometabolism and neuropathological correlates in brains of dementia with Lewy bodies

Cerebral glucose metabolism using positron emission tomography (PET) with (18)F-fluorodeoxyglucose was examined in 11 patients with probable Alzheimer's disease (AD), 6 patients with probable, and 1 patient with autopsy-confirmed dementia with Lewy bodies (DLB) as well as in 10 age-matched normal control subjects. Among widespread cortical regions showing glucose hypometabolism 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 (mean-2 SD of normal control subjects), DLB could be distinguished from AD with a sensitivity of 86% and a specificity of 91%. In contrast, apolipoprotein E4 allele frequency and cerebrospinal fluid tau levels did not differ significantly between the two groups. In order to further dissect out neuropathological correlates of the dysfunctional occipital lobe, postmortem brains from 19 patients with AD and 17 with DLB as well as 11 brains from normal controls were examined. A distinct and extensive spongiform change with coexisting gliosis was variably noted throughout cerebral white matter with relative sparing of gray matter in DLB. Notably, the white matter spongiform change and gliosis was most prominently and consistently found in the occipital region of DLB, and the severity of the spongiform change in each brain region generally paralleled to the regional difference in reduced glucose metabolism between the living AD and DLB patients. These findings suggest that (1) among several potential antemortem biomarkers in the diagnosis of DLB, measures of the glucose metabolism in the occipital cortex may be an informative diagnostic aid to distinguish DLB from AD; and (2) a pathological process that generates widespread spongiform change and gliosis in long projection fibers may contribute, at least in part, to the characteristic imaging features of DLB.     

Neuropathological investigation of the hypometabolic regions on positron emission tomography with [18F] fluorodeoxyglucose in patients with dementia with Lewy bodies

We performed a quantitative neuropathological examination of the hypometabolic regions on FDG PET in dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and control cases. When the DLB cases were divided into two groups according to concomitant AD pathology (ADP), neuronal loss in the temporo-parietal association area was milder in the DLB groups than in the AD group, although there were no differences between the two DLB groups. Tau and Aβ immunoreactivities were observed in the AD group and the DLB group with ADP, but were rare in the DLB group without ADP. Tau and Aβ immunoreactivities as well as numbers of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) were more common in the AD group than in the DLB group with ADP. There was no difference in neuronal loss in the occipital area among the three groups. α-Synuclein immunoreactivity was observed in the DLB groups but not in the AD group. There were no differences in α-synuclein immunoreactivity and number of Lewy bodies (LBs) between the two DLB groups. These findings indicate that the neuropathological bases of the hypometabolic regions in the temporo-parietal association and occipital area in DLB may be AD pathology and Lewy pathology, respectively.     

Cerebral blood flow in Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease according to three-dimensional stereotactic surface projection imaging

Regional brain perfusion was analyzed using single-photon emission computed tomography with three-dimensional stereotactic surface projections (3D-SSP) in 69 patients with Parkinson's disease (PD), 16 patients with dementia with Lewy bodies (DLB) and 15 patients with Alzheimer's disease (AD), and compared with that in 24 age-equivalent normal subjects. Nondemented PD patients revealed less parietal and frontal flow than controls. With mental impairment, flow reduction extended to other areas including occipital regions. PD with dementia and DLB showed similar reduction patterns, although frontal flow showed a greater reduction in DLB. AD showed little occipital reduction, but a severe parieto-temporal reduction. Thus, 3D-SSP appears to be useful in the detection of cortical lesions and the differential diagnosis of patients with cognitive impairment.     

99mTc-ethyl cysteinate dimer brain SPECT findings in early stage of dementia with Lewy bodies and Parkinson's disease patients: a correlation with neuropsychological tests

We examined clinical presentations, neuropsychological findings, and perfusion patterns of ^99mTc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients with early stage dementia with Lewy bodies (DLB) ( n  = 17) and Parkinson's disease (PD) ( n  = 16), with age-matched healthy controls ( n  = 10). Seven paired regions of interest (ROIs) were drawn manually including inferior frontal, temporal, parietal, occipital, parieto-occipital junction, striatum and thalamus for semiquantitative measurement. Neuropsychological tests were applied for clinical correlation. The SPECT results showed significant hypoperfusion in DLB group in frontal, parietal, thalamus, temporal ROIs compared with controls ( P  < 0.01) whilst signals in temporal areas was significantly reduced compared with PD group ( P  < 0.05). Neuropsychological tests showed that DLB patients had deficits in mental manipulation, short-term memory, abstract thinking, drawing and semantic verbal fluencies ( P  < 0.05, compared with control). In addition, DLB group had lower scores than those with PD in mental manipulation, drawing and semantic verbal fluency ( P  < 0.05). Our study showed that even in early stages of DLB, neuropsychological and perfusion patterns were evident and may be different from PD group, despite they shared certain similarities both in neuropsychological and image findings compared with age-matched controls.     

Diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease

Dementia with Lewy bodies (DLB) is a common form of dementia, with fewer memory deficits, and more visuo-perceptual problems than Alzheimer's disease (AD). We hypothesized that there would be disease specific alterations revealed by diffusion tensor imaging with AD showing temporal lobe and DLB more parietal changes. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with diffusion tensor FLAIR imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were calculated, and data were analysed using pre-defined regions of interest (ROI) and also with SPM. We found a significant decrease in the FA map in a ROI in the parietal lobe (precuneus) of the DLB group. Using SPM we found increased ADC in the left temporal lobe of AD subjects compared to controls. There were no other significant differences between groups. We conclude that there are subtle changes visible with diffusion imaging in DLB and AD which may reflect disrupted connectivity and underlie observed perfusion changes in these disorders.     

Dementia with Lewy bodies and AD are not associated with occipital lobe atrophy on MRI.

Dementia with Lewy bodies (DLB) is associated with occipital changes in blood flow and metabolism, but structural changes in this region have not previously been assessed. The authors performed volumetric MRI measurement of the occipital lobe blind to the diagnosis in 23 subjects with DLB, 25 with AD, and 24 age-matched control subjects. There were no significant differences between groups in occipital lobe volume. The authors conclude gross structural changes in the occipital lobe do not occur in patients with mild to moderate DLB or AD.     

A multiparametric MRI study of structural brain damage in dementia with lewy bodies: A comparison with Alzheimer's disease

IntroductionDifferential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is crucial for an adequate patients' management but might be challenging. We investigated with advanced MRI techniques gray (GM) and white matter (WM) damage in DLB patients compared to those with AD.Methods24 DLB patients, 26 age- and disease severity-matched AD patients, and 20 age and sex-matched controls performed clinical and neuropsychological assessment, and brain structural and diffusion-tensor MRI. We measured GM atrophy using voxel-based morphometry, WM hyperintensities (WMH) using a local thresholding segmentation technique, and normal-appearing WM (NAWM) damage using tract-based spatial statistic.ResultsDLB and AD patients exhibited mild-to-moderate-stage dementia. Compared to controls, GM damage was diffuse in AD, while limited to bilateral thalamus and temporal regions in DLB. Compared to DLB, AD patients exhibited GM atrophy in bilateral fronto-temporal and occipital regions. DLB and AD patients showed higher WMH load than controls, with no differences among each other. WMH in DLB were diffuse with relative prevalence in posterior parietal-occipital regions. Compared to controls, both DLB and AD patients showed reduced microstructural integrity of the main supratentorial and infratentorial NAWM tracts. AD patients exhibited greater posterior NAWM damage than DLB.ConclusionsDLB showed prominent WM degeneration compared to the limited GM atrophy, while in AD both tissue compartments were severely involved. In DLB, NAWM microstructural degeneration was independent of WMH, thus revealing two possible underlying processes. Different pathophysiological mechanisms are likely to drive GM and WM damage distribution in DLB and AD.     

18F]FDG-PET study in dementia with Lewy bodies and Alzheimer's disease

1. The authors report two siblings with dementia with Lewy bodies (DLB). Both the older brother and the younger sister underwent positron emission tomography (PET) studies with [18F]-2-fluoro-deoxy-D-glucose (FDG) during life. The FDG-PET study demonstrated unique and pronounced metabolic impairment in the occipital cortex in both patients. The clinical diagnosis of DLB in the sister was confirmed by autopsy. 2. FDG-PET images from 11 patients with Alzheimer's disease (AD), 7 patients with DLB and 10 age-matched normal subjects were obtained and analyzed by the statistical parametric mapping (SPM) method. The SPM demonstrated a widespread metabolic reduction in the DLB group. The reduction was particularly pronounced in the visual association cortex in the DLB group compared to the AD group irrespective of clinical severity of the disease. 3. These findings suggest that functional neuroimaging techniques, including FDG-PET, will provide a valuable diagnostic aid to differentiate DLB from AD, and this will help detect DLB patients in the early stage of the disease.     

A SPECT study of apathy in Alzheimer's disease

BACKGROUND/AIMS: To assess the association between regional cerebral blood flow (rCBF) and apathy in Alzheimer's Disease (AD). METHODS: SPECT and MRI scans were obtained from 51 nondepressed outpatients meeting criteria for probable AD (age 77.6 +/- 6.6 years; MMSE 22.3 +/- 5.1; 23 apathetic, 28 nonapathetic) and 23 healthy elderly (75.6 +/- 3.8 years) controls. The following regions of interest (ROIs) were compared between apathetic and nonapathetic AD patients and then referenced against aged controls: anterior cingulate, orbitofrontal cortex, middle medial temporal cortex, hippocampus, medial superior temporal cortex, thalamus/hypothalamus and pons. RESULTS: Apathetic and nonapathetic patients had significant differences in rCBF. Relative to nonapathetic AD patients, apathetic AD patients had lower perfusion in 2 ROIs (right orbitofrontal cortex and left anterior cingulate) and higher perfusion in 5 ROIs (right and left hippocampi, left medial superior temporal gyrus, and right and left middle medial temporal cortex). Comparison of rCBF in these 7 ROIs to healthy elderly controls confirmed hypoperfusion in the left anterior cingulate and right orbitofrontal cortex and suggested a relative sparing of perfusion among apathetic AD patients in the remaining 5 ROIs. CONCLUSIONS: In this group of nondepressed patients with AD, apathetic subjects displayed significant perfusion differences compared to nonapathetic subjects.