Correlation between pathology and neuromelanin MR imaging in Parkinson’s disease and dementia with Lewy bodies

Introduction

Direct correlation between neuropathological findings and postmortem neuromelanin MR imaging (NmMRI) was performed in the substantia nigra pars compacta (SNc) to clarify the pathological background of the signal changes in normal, Parkinson’s disease (PD), and dementia with Lewy bodies (DLB) cases.

Methods

NmMRI of 10 % formalin-fixed autopsied midbrains was performed in three cases (normal control, DLB, and PD) with a 3T imaging system, using a 3D gradient echo T1-weighted sequence with a magnetization transfer contrast pulse. Neuropathological examinations of the midbrains were performed, and the density of neuromelanin-positive neurons (number per square millimeter) was determined. The extent of iron deposition in the midbrain was also evaluated using ferritin immunohistochemistry. Furthermore, we directly correlated the contrast signal ratio in the SNc and the density of neuromelanin-containing neurons.

Results

Diffuse hyperintense areas in the SNc reflected well-preserved neuromelanin-containing neurons in the normal control case, whereas an iso-intense area in the SNc showed severe loss of neuromelanin-containing neurons in the DLB and PD cases. Increased signal intensity in the SNc was apparently not influenced by iron deposition. Furthermore, a significant positive correlation between signal intensity and the density of neuromelanin-containing neurons was seen in the SNc.

Conclusion

Based on the direct correlation between postportem NmMRI and neuropathological findings, signal intensity in the SNc is closely related to the quantity of neuromelanin-containing neurons but is not influenced by iron deposition.     

Distinct perfusion patterns in Alzheimer’s disease,frontotemporal dementia and dementia with Lewy bodies

Objectives

To compare pseudo-continuous arterial spin-labelled (PCASL) magnetic resonance imaging (MRI) measured quantitative cerebral blood flow (CBF) of patients with frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), Alzheimer’s disease (AD) and controls, in a region of interest (ROI) and voxel-wise fashion.

Methods

We analysed whole-brain 3D fast-spin-echo PCASL images of 20 FTD patients, 14 DLB patients, 48 AD patients and 50 controls from the Amsterdam Dementia Cohort. Regional CBF patterns were compared using analyses of variance for repeated measures. Permutation tests were used for voxel-wise comparisons. Analyses were performed using uncorrected and partial volume corrected (PVC) maps. All analyses were corrected for age and sex.

Results

There was an interaction between diagnosis and region (p?Conclusions Patients with AD, FTD and DLB display distinct patterns of quantitative regional CBF changes. 3D-PCASL may provide additional value in the workup of dementia patients.

Key points

? Patterns of regional CBF changes differ between AD, FTD and DLB patients ? CBF is lower throughout the brain in DLB than AD and FTD ? 3D-PCASL MRI is a potential non-invasive and easily accessible alternative to FDG-PET ? 3D-PCASL MRI may be of additional value in the workup of dementia     

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease

Purpose Both decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac ¹²³I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimers disease (AD).Methods The study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[¹²³I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections.Results Medial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT.Conclusion MIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.An editorial commentary on this paper is available at     

The effect of levodopa therapy on dopamine transporter SPECT imaging with 123I-FP-CIT in patients with Parkinson’s disease

Purpose The aim of this study was to evaluate, by means of ¹²³I-FP-CIT SPECT, the effect of chronic treatment with levodopa on striatal dopamine transporter (DAT) in patients with Parkinsons disease.Methods Fifteen patients under stable levodopa/carbidopa monotherapy were imaged twice: at baseline on medication and after at least 20 days of treatment wash-out. DAT levels were assessed from SPECT imaging for the entire striatum, the right and left striatum, the right and left putamen and the right and left caudate, as a ratio of regional brain activities using the formula: (striatal region of interest–occipital)/occipital.Results During levodopa wash-out, despite a worsening in patients clinical disability (H&Y mean stage 2.53±0.58 versus 1.73±0.45 on therapy, p<0.001), striatal ¹²³I-FP-CIT levels were not significantly different from those at baseline in any of the brain regions examined.Conclusion The results of this study suggest that levodopa does not affect ¹²³I-FP-CIT brain imaging and confirm that it is not necessary to withdraw this medication to measure DAT levels with SPECT.     

Quantitative simultaneous 99mTc-ECD/123I-FP-CIT SPECT in Parkinson’s disease and multiple system atrophy

Purpose The purpose of this study was to investigate the feasibility and utility of dual-isotope SPECT for differential diagnosis of idiopathic Parkinsons disease (IPD) and multiple system atrophy (MSA).Methods Simultaneous ^99mTc-ECD/¹²³I-FP-CIT studies were performed in nine normal controls, five IPD patients, and five MSA patients. Projections were corrected for scatter, cross-talk, and high-energy penetration, and iteratively reconstructed while correcting for patient-specific attenuation and variable collimator response. Perfusion and dopamine transporter (DAT) function were assessed using voxel-based statistical parametric mapping (SPM2) and volume of interest quantitation. DAT binding potential (BP) and asymmetry index (AI) were estimated in the putamen and caudate nucleus.Results Striatal BP was lower in IPD (55%) and MSA (23%) compared to normal controls (p<0.01) , and in IPD compared to MSA (p<0.05). AI was greater for IPD than for MSA and controls in both the caudate nucleus and the putamen (p<0.05). There was significantly decreased perfusion in the left and right nucleus lentiformis in MSA compared to IPD and controls (p<0.05).Conclusion Dual-isotope studies are both feasible in and promising for the diagnosis of parkinsonian syndromes.     

Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson’s disease

Purpose

The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson’s disease (PD) patients.

Methods

Twenty-six de novo untreated PD patients were scanned with ¹²³I-FP-CIT SPECT and ¹⁸F-FDG PET. The dopaminergic impairment was measured with putaminal ¹²³I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP_OSEM) and the least-squares (LS) method (BP_LS). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc.

Results

The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP_OSEM and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP_LS and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p?<?0.05, corrected for multiple comparison).

Conclusions

Putaminal BP_LS is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects.     

Validation of the cingulate island sign with optimized ratios for discriminating dementia with Lewy bodies from Alzheimer’s disease using brain perfusion SPECT

Objective

Dementia with Lewy bodies (DLB) is often cited as the second most common dementia after Alzheimer’s disease (AD). It is clinically important to distinguish DLB from AD because specific side effects of antipsychotic drugs are limited to DLB. The relative preservation of cingulate glucose metabolism in the posterior cingulate gyri versus that in the precuni, known as the cingulate island sign (CIS), in patients with DLB compared with AD is supposed to be highly specific for diagnosing DLB. In a previous study, using brain perfusion SPECT, the largest value (0.873) for the area under the receiver operating characteristic (ROC) curve (AUC) for differentiating DLB from AD was obtained with the ratio of the posterior cingulate gyri from an early Alzheimer’s disease-specific hypoperfusion volume of interest (VOI) versus the medial occipital lobe. Two purposes of this study are as follows: one is optimization of VOI setting for calculating CIS values and the other is to evaluate their accuracy and simultaneously to retest the method described in our previous paper.

Methods

We conducted a retest of this SPECT method with another cohort of 13 patients with DLB and 13 patients with AD. Furthermore, we optimized VOIs using contrast images obtained from group comparisons of DLB and normal controls; the same 18 patients with DLB and 18 normal controls examined in our previous study. We obtained DLB-specific VOIs from areas where brain perfusion was significantly decreased in DLB. As the numerators of these ratios, early Alzheimer’s disease-specific VOIs were used after subtracting DLB-specific VOIs. The DLB-specific VOIs were used as the denominator.

Results

In retest, the obtained AUC was 0.858 and the accuracy, sensitivity, and specificity were 84.6, 84.6, and 84.6%, respectively. The ROC curve analysis with these optimized VOIs yielded a higher AUC of 0.882; and the accuracy, sensitivity, and specificity of these new CIS ratios were 84.6, 92.3, and 76.9%, respectively, with a threshold value of 0.281.

Conclusion

Optimized CISs using brain perfusion SPECT are clinically useful for differentiating DLB from AD.

     

Fully automatic differential diagnosis system for dementia with Lewy bodies and Alzheimer’s disease using FDG-PET and 3D-SSP

Purpose To evaluate a fully automatic computer-assisted diagnostic system for mild dementia with Lewy bodies (DLB), permitting distinction from mild Alzheimer’s disease (AD). Methods Using ¹⁸F-fluorodeoxyglucose and positron emission tomography (FDG-PET), glucose metabolic images were obtained from mild DLB and mild AD patients. Two groups consisting of 16 mild DLB patients and 21 mild AD patients were recruited for diagnostic evaluation between mild DLB and mild AD. The mean age ± SD of the mild DLB group and the mild AD group was 74.3 ± 4.9 and 71.7 ± 2.1 years, respectively, and the mean scores of the MMSE for the mild DLB and the mild AD group were 21.7 ± 1.9 and 23.1 ± 2.1, respectively. A receiver operating characteristic (ROC) analysis was performed to compare the diagnostic performance, in terms of discrimination between DLB and AD, of conventional axial FDG-PET images inspected visually by experts and beginners with that of our fully automatic diagnosis system using the statistical brain mapping method and Z scores obtained with the DLB template. Results The diagnostic performance of the automatic system was comparable to that of visual inspection by experts. The area under the ROC curve for the automatic diagnosis system was 0.77. The mean area under the ROC curve for visual inspection by experts and beginners was 0.76 and 0.65, respectively. Conclusion The fully automatic differential diagnosis system for distinction between mild DLB and AD showed a similar diagnostic accuracy to visual inspection by experts. It would be a useful diagnostic tool to distinguish mild DLB from mild AD in clinical practice.     

Comparison of 123I-MIBG myocardial scintigraphy,brain perfusion SPECT,and voxel-based MRI morphometry for distinguishing between dementia with Lewy bodies and Alzheimer’s disease

Objective

This study aimed to compare the diagnostic value of ¹²³I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, N-isopropyl-p[¹²³I]iodoamphetamine (IMP) brain perfusion single-photon emission computed tomography (SPECT), and brain magnetic resonance imaging (MRI) voxel-based morphometry (VBM) for the differentiation of dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD).

Methods

Thirty-five and 34 patients with probable DLB and probable AD, respectively, were enrolled. All patients underwent ¹²³I-MIBG myocardial scintigraphy, ¹²³I-IMP brain perfusion SPECT, and brain MRI. For ¹²³I-MIBG imaging, we calculated early and delayed heart-to-mediastinum (H/M) uptake ratios. Three-dimensional stereotactic surface projections (3D-SSP) were used to analyze the results of ¹²³I-IMP SPECT. VBM with statistical parametric mapping 8 plus diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) was used to analyze the brain MRI data.

Results

The area under the receiver operating characteristic curves (AUC) for discriminating DLB and AD was highest (0.882) for the delayed H/M ratio on ¹²³I-MIBG scintigraphy. AUC for z-score measurement in the occipital lobe was 0.818 and that for the extent of gray matter (GM) atrophy in the whole brain was 0.788. AUC for the combination of 3D-SSP and VBM analysis was 0.836. The respective sensitivities and specificities for distinguishing DLB from AD were 97.1 and 100 % for the delayed H/M ratio using ¹²³I-MIBG scintigraphy; 88.6 and 73.5 % for the occipital lobe z-score using 3D-SSP analysis; 85.7 and 64.7 % for the extent of whole brain GM atrophy using voxel-based MRI morphometry; and 91.4 and 76.5 % for the combination of 3D-SSP analysis and VBM.

Conclusions

¹²³I-MIBG myocardial scintigraphy was superior to brain perfusion SPECT and brain MRI using an advanced statistical technique to differentiate DLB and AD.     

Comparison of two neural network classifiers in the differential diagnosis of essential tremor and Parkinson’s disease by 123I-FP-CIT brain SPECT

Purpose  

To contribute to the differentiation of Parkinson’s disease (PD) and essential tremor (ET), we compared two different artificial neural network classifiers using ¹²³I-FP-CIT SPECT data, a probabilistic neural network (PNN) and a classification tree (ClT).     

Immediate effects of treadmill walking in individuals with Lewy body dementia and Huntington’s disease

BackgroundTreadmill training may improve gait disorders associated with neurodegenerative diseases. In Parkinson’s disease (PD), treadmill training alters gait patterns after one session, and long-term training improves gait parameters, fall risk, and quality of life.Research questionWhat is the feasibility and safety of using this intervention for people with Lewy body dementia (LBD) or Huntington’s disease (HD)?MethodsIn this observational study, 10 individuals with HD, 8 individuals with LBD, and 10 control individuals walked for 20 min on a treadmill using a speed dependent protocol starting at a slow comfortable speed and increasing incrementally toward their normal overground speed. Feasibility was determined by compliance to protocol and safety by no incidents of abnormal vital signs or expressions of distress. Changes in gait measures, Timed Up and Go (TUG) scores and quantitative motor function measures (Q-Motor; precision grasp force variability, finger and foot tapping frequency) before and after treadmill walking were analyzed using linear models.ResultsTreadmill training is feasible and safe in LBD and HD; although, participants could not initiate treadmill walking at their comfortable overground speeds, and only 3 participants with HD were able to achieve their overground walking speed within the 20-minute session. No changes in gait measures, TUG times, and Q-Motor measures were found among LBD and HD participants after treadmill walking, although control participants demonstrated significant increases in several gait measures, and foot tap frequency (estimated difference = 0.290; p = 0.026).SignificanceLonger and more frequent treadmill sessions may be needed to see gait and motor function effects in LBD and HD. Motor and cognitive impairments associated with these diseases may make them less amenable to the effects of treadmill training.     

SPECT neuroimaging and neuropsychological functions in different stages of Parkinson’s disease

Purpose  

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson’s disease (PD).     

Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson’s disease

Purpose Diagnosis of Parkinsons disease (PD) can be difficult. F-DOPA PET is able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system.Methods Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the off state (UPDRS-III and H&Y stage).Results Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake (r=0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake (r=0.84, both p<0.0001). Both striatal uptake of FP-CIT and that of F-DOPA correlated moderately with H&Y stage (=–0.52 for both techniques), UPDRS-III (=–0.38 for F-DOPA; =–0.45 for FP-CIT) and disease duration (=–0.59 for F-DOPA; =–0.49 for FP-CIT, all p<0.05).Conclusion FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD.     

Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson’s disease and healthy controls

Purpose  Diagnosing Parkinson’s disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. Methods  Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. Results  FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. Conclusion  FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity.     

Monoamine transporter availability in Parkinson’s disease patients with or without depression

Purpose  Depression is a common symptom in patients suffering from Parkinson’s disease (PD) and markedly reduces their quality of life. As post-mortem studies have shown, its presence may reflect extensive cell loss in the midbrain and brainstem with imbalances in monoaminergic neurotransmitters. However, in vivo evidence of specific monoaminergic deficits in depressed PD patients is still sparse. Therefore, we studied PD patients with depression (PD+D) and without depression (PD−D) using high-resolution single-photon emission computed tomography (SPECT) and the monoamine transporter marker [¹²³I]FP-CIT. Methods  A magnetic resonance imaging-based region-of-interest analysis was applied to quantify the specific-to-nondisplaceable [¹²³I]FP-CIT binding coefficient V₃″ in the striatum, thalamus and midbrain/brainstem regions. Results  PD+D patients had significantly lower V₃″ compared with PD−D patients in the striatum (p<0.001), thalamus (p=0.002), and midbrain/brainstem (p=0.025). Only PD+D patients without selective serotonin reuptake inhibitor (SSRI) treatment showed lower thalamic and midbrain V₃″ than controls (p<0.001, p=0.029). In a small sub-group of SSRI-treated PD+D patients neither thalamic V₃″ nor midbrain/brainstem V₃″ differed from those in PD−D patients (p=0.168, p=0.201) or controls (p=0.384, p=0.318). Conclusion  Our data indicate that depression in PD is associated with a more pronounced loss of striatal dopamine transporter availability that is most likely secondary to increased dopaminergic degeneration. In addition, depressed PD patients have a lower availability of midbrain/brainstem monoamine transporters than nondepressed PD patients. These findings provide in vivo evidence in support of the known post-mortem data demonstrating more extensive nerve cell loss in PD with depression and indicate that SPECT imaging can help to identify pathophysiological changes underlying nonmotor symptoms in this common movement disorder. The results of this study were partly presented at the Amersham Healthcare User Meeting during the 40^th Annual Meeting of the German Society of Nuclear Medicine 2002 in Freiburg, Germany, and at the 54^th Annual Congress of the Society of Nuclear Medicine 2007 in Washington, DC, USA.     

Early-stage [123I]β-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson’s disease

Purpose Previous studies using dopamine transporter single-photon emission computed tomography (SPECT) to try and distinguish between patients with idiopathic Parkinsons disease (IPD) and patients with atypical parkinsonian syndromes (APS) have mainly focussed on patients with an already established clinical diagnosis of several years duration. Differences in the pattern of striatal involvement between IPD and APS have been found in only few studies. We hypothesized that distinguishing SPECT features might be most pronounced at an early disease stage, and the purpose of the present study was to investigate this hypothesis.Methods The study included 72 patients with an initial clinical diagnosis of IPD, supported by decreased striatal [¹²³I]-CIT binding on baseline SPECT. In ten patients, the diagnosis was changed to APS over a mean follow-up period of 62 months. We retrospectively compared the patterns of striatal involvement on the baseline SPECT scans between the group of patients (re)diagnosed with APS and the remaining 62 patients in whom a diagnosis of IPD was maintained.Results In the group of patients with APS, baseline [¹²³I]-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups.Conclusion [¹²³I]-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual cases.     

Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific

The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson’s disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63±9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61±0.29) was significantly lower than that in the control group (2.24±0.14, P<0.01), P-nism (2.15±0.31, P<0.01), MSA (2.08±0.31, P<0.05) and PSP (2.30±0.24, P<0.01). The delayed H/M ratio in PD (1.47±0.34) was also significantly lower than that in the control group (2.37±0.14, P<0.01), P-nism (2.13±0.38, P<0.01), PSP (2.36±0.36, P<0.01) and MSA (2.17±0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%±8.0% vs 11%±4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of the lower leg muscles in MSA were significantly lower than those in the control group (P<0.05). In conclusion: In patients with PD without autonomic failure, only cardiac MIBG uptake was severely reduced in the earliest phase of the disease (stage I). Parkinsonian syndromes other than PD did not demonstrate significant reduction in MIBG uptake in any organs except for the lower legs in MSA. In patients with PD without autonomic failure, reduction in MIBG uptake occurs selectively in the heart; this is considered to be a specific finding for PD and useful for the differential diagnosis of the parkinsonian syndromes. Received 13 September and in revised form 29 December 1999     

Cerebral blood flow changes in Parkinson?s disease associated with dementia

Dementia is one of the main non-motor symptoms of Parkinson's disease (PD) and it is diagnosed in about 30% of cases. Its aetiology remains unclear and contributing factors are controversial. Dementia may be more common in old patients with severe motor symptoms and mild cognitive impairment. Clinico-pathological studies show the association between dementia in PD and the age-related group of dementias, such as AD and VaD. A valuable aid in the assessment of dementia in PD is cerebral blood flow (CBF) brain SPECT scanning. It shows three different patterns of rCBF reduction, including frontal lobe hypoperfusion, Alzheimer-like type of hypoperfusion and multiple, vascular defects. The heterogeneity of rCBF reduction may reflect the multifactorial pathophysiology of dementia in PD. It may result from concomitant AD pathology, cerebrovascular disease, destruction of nigro-striato-frontal projection or may be a distinct disease of different aetiology.