Alzheimer's disease and frontotemporal dementia are differentiated by discriminant analysis applied to (99m)Tc HmPAO SPECT data

OBJECTIVE: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most frequent neurodegenerative cognitive disorders. However, FTD remains poorly recognised clinically. The use of (99m)HmPAO-single photon emission computed tomography (SPECT) has been demonstrated in the differentiation of AD and FTD. Nethertheless, there are very few comparative studies designed to assess its precise value in this differential diagnosis. The aim was to determine a simple decision rule, deduced from statistical analysis, which, if applied to regions of interest (ROIs) and mini mental state examination (MMSE), could improve the predictive value of SPECT in differential diagnosis between AD and FTD. METHODS: Forty patients, 20 with probable AD and 20 with probable FTD were included. All patients underwent brain SPECT imaging, after an intravenous injection of (99m)Tc HmPAO-(555mBq). For each patient, 20 ROIs were determined on the Fleishig's slice and their activity was normalised to the mean cerebellar activity. Bivariate analysis (Wilcoxon rank tests) and multivariate analysis (stepwise discriminant analysis) were performed to determine the subgroup of variables able to give the highest predictive value for this differential diagnosis. A simple decision rule was built from a predictive score derived by factorial discriminant analysis. RESULTS: As previously described, the fixation defect was found in frontal regions of interest (ROIs) in FTD and in the left temporoparietal-occipital ROIs in AD. Among the 21 variables, five were finally selected: right median frontal, left lateral frontal, left tempoparietal, left temporoparietal-occipital areas, and MMSE. One hundred per cent of patients with FTD were correctly classified by the decision rule (20/20 patients) and 90% of patients with AD (18/20). CONCLUSION: AD and FTD are differentiated by SPECT. Automatic classification based on a decision rule deduced from factorial discriminant analysis could enhance its performance.     

99mTc-Hexamethylpropylene amine oxime SPECT and X-ray CT in acute cerebral ischaemia

Summary Early diagnosis of acute cerebral ischaemia is still unsatisfactory, because X-ray computed tomography (CT) does not reveal the site and extent of hypoperfusion within the first 24h. Single photon emission computed tomography (SPECT) using ^99mTc-hexamethylpropylene amine oxime (HMPAO) may offer earlier information, since the distribution of HMPAO follows the actual cerebral perfusion pattern. We therefore investigated 53 patients suffering from acute cerebral ischaemia (10 with transient ischaemic attacks, 9 with prolonged ischaemic reversible neurological deficits, 34 with completed stroke). SPECT and CT examinations were performed on days 1, 3, and 14. On day 1, SPECT revealed hypoperfused areas in 42 patients, whereas CT showed hypodensities only in 5. The sensitivity of SPECT was higher in cortical compared with subcortical ischaemia. In patients suffering from reversible neurological deficits SPECT normalized in the follow-up, corresponding to clinical improvement. In completed stroke, SPECT demonstrated variable perfusion patterns with hypo-, normo-, and hyperperfused areas on day 3 and especially on day 14. In contrast to CT, HMPAO SPECT leads to early diagnosis of cerebral ischaemia, in particular within the cerebral cortex.     

SPECT findings in Alzheimer's disease and Parkinson's disease with dementia

We examined, with single photon emission tomography (SPECT) and (^99mTc)-HMPAO, 18 patients with idiopathic Parkinson's disease and no dementia (PD), 12 patients with PD and dementia, 24 patients with probable Alzheimer's disease (AD) and 14 controls. While the three patient groups showed significantly lower perfusion in frontal inferior and temporal inferior areas as compared to controls, both demented groups showed significantly more severe bilateral hypoperfusion in superior frontal, superior temporal and parietal areas as compared to non-demented PD patients and controls. On the other hand, no significant differences in cerebral perfusion were found between patients with AD and patients with PD and dementia. In conclusion, our findings demonstrated specific but similar cerebral perfusion deficits in demented patients with either AD or PD.     

Alzheimer's disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia

OBJECTIVE: To compare the HMPAO SPECT cerebral perfusion patterns in early and late onset Alzheimer's disease. METHODS: Twenty patients with early onset disease (<65 years) and 44 patients with late onset disease (>65 years) were studied. All patients fulfilled NINCDS-ADRDA clinical criteria and had details of disease severity and length of history at the time of imaging. Technetium-99m HMPAO SPECT brain scans were acquired on a multi-detector gammacamera and analysed visually and with statistical parametric mapping (SPM99). RESULTS: Patients with early onset disease had significantly greater posterior cortical association area involvement whereas those with late onset disease had significantly greater medial temporal hypoperfusion. These findings were unchanged after controlling for disease severity and length of illness. DISCUSSION: These functional imaging findings of the differences between early and late onset Alzheimer's disease are supported by published findings that include histopathological and clinical evidence; namely late onset patients tend to present with the characteristic involvement of the medial temporal lobes producing marked memory loss whereas early onset patients present with predominant posterior cortical association area involvement. These age related findings should be borne in mind when clinically diagnosing, and interpreting functional brain imaging studies in, patients with suspected Alzheimer's disease.     

Fluency deficits in patients with Alzheimer's disease and frontal lobe lesions

Fluency tests are widely used in clinical settings to assess cognitive function. Fluency deficits In patients with Alzheimer's disease (AD) are generally attributed to deteriorated language storage. In contrast, patients with lesions to the frontal lobes (FL) of the brain are thought to have poor fluency due to executive deficits of retrieval. This study examined the relationships between fluency performance and cognitive measures of language and executive function in both AD and FL patients. In both groups, fluency performance related to measures of language comprehension and executive control of attention. However, in AD patients, fluency deficits were most closely associated with language and verbal memory deterioration, while in FL patients fluency deficits were more strongly associated with executive measures of strategic planning and attention. Qualitatively different patterns of functional deficits may influence fluency performance in different neuropsychological groups. Caution is therefore urged in the interpretation of poor fluency scores as indicative of either language or executive dysfunction, without additional information about the reasons for poor performance.     

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.     

A discrepancy between Tc-99m HMPAO SPECT and Tc-99m ECD SPECT in Creutzfeldt-Jacob disease.

We observed a discrepancy between the perfusion patterns seen in single photon emission computed tomography (SPECT) images obtained using technetium-99m hexamethyl propylene amine oxime (HMPAO) and SPECT images obtained using technetium-99m ethyl cysteinate dimer (ECD) in an 84-year-old man with Creutzfeldt-Jacob disease (CJD). HMPAO-SPECT demonstrated a reduction in perfusion in the parieto-temporal regions, especially the left temporal area. However, ECD-SPECT revealed a significant reduction in the bifrontal regions. At autopsy, the characteristic pathological findings of CJD, spongiform vacuolation, were most prominent in the bifrontal regions. Thus, the clinical features and the pathological findings were more closely correlated with the ECD-SPECT images than the HMPAO-SPECT images.     

Metamemory accuracy in Alzheimer's disease and frontotemporal lobe dementia

Metamemory is a multifaceted concept, which deals with an individual's knowledge and control of his or her own memory system. The ability to monitor memory performance accurately was examined in 16 patients with Alzheimer's disease (AD), 6 patients with frontotemporal lobe dementia (FTD) and 16 elderly subjects. Participants made global memory predictions in a single experimental task, both prior to and after studying 20 critical cue-target words. Prediction accuracy was evaluated with traditional score-difference measures. Our data showed that in the case of the after-study prediction FTD patients were more inaccurate in predicting their memory performance than were the AD patients, suggesting that FTD patients were more impaired than AD patients in monitoring their memory performance. Nevertheless, there seems to be no difference regarding their metacognitive knowledge or beliefs of their own memory, as indicated by the absence of difference in prediction accuracy made before study. Moreover, analyses of covariance showed that the difference in metamemory performance between AD and FTD may be related to the executive differences observed in these two populations. In sum, our results suggest that metamemory evaluation could be useful to distinguish between patients with AD and those with FTD.     

Clusters of cognitive and behavioral disorders clearly distinguish primary progressive aphasia from frontal lobe dementia, and Alzheimer's disease

BACKGROUND/AIMS: Frontal lobe dementia (FLD) and primary nonfluent progressive aphasia (PnPA) are two forms of frontotemporal lobe degeneration. The relationship between these conditions remains unclear. Our study aimed to better define the behavioral and cognitive clusters characterizing PnPA patients. METHODS: We cognitively and behaviorally evaluated three groups of newly diagnosed patients affected by Alzheimer's disease (AD, n=20), FLD (n=22) and PnPA (n=10), in order to assess the cognitive-behavioral pattern of PnPA, compared to both FLD and AD. RESULTS: We found, as expected, worse performances in episodic memory in AD, of both the verbal fluency and naming tasks in PnPA, while FLD mainly showed behavioral disorders associated with an unremarkable deficit in the executive tasks. PnPA was not characterized by any significant behavioral disorders. Factor analysis-extracted three main factors ('mnesic', 'behavioral' and 'linguistic') clearly correlated to each group. A discriminant analysis based on the extracted factors correctly classified 84.6% of all patients. CONCLUSION: The evidence of a characteristics cognitive profile, without any significant behavioral changes, highlights that PnPA is different from other forms of frontotemporal lobe degeneration regarding both the cognitive and behavioral patterns; thus, it should be considered independently in further studies.     

Utility of (99m)Tc-HM-PAO SPECT hippocampal image to diagnose early stages of Alzheimer's disease using semiquantitative analysis

OBJECTIVE: Examination of the utility of (99m)Tc-hexamethylpropylene amine oxide ((99m)Tc-HM-PAO) SPECT hippocampal image to diagnose early stages of Alzheimer's disease (AD) using semiquantitative analysis. SUBJECTS: 10 early-stage AD patients and 8 normal sex-matched elderly controls. SETTING: Outpatient division of the Ehime University Hospital. METHOD: We performed (99m)Tc-HM-PAO SPECT perfusion imaging in each subject. A semiquantitative method of assessing regional variation was used. The regions of interest for temporal regions were set at images parallel to the long axis of the hippocampal formation which were reconstructed at 30 degrees negative to the orbitomeatal line and those for other regions were set on ordinary transaxial images. RESULTS: The regional cerebral blood flow ratio of the bilateral medial temporal lobe at the hippocampal image was significantly lower in the AD subjects than in the normally aged controls without any other differences in ordinary transaxial images. CONCLUSION: This study suggests that (99m)Tc-HM-PAO SPECT hippocampal images might be a helpful tool for the diagnosis of very-early-stage AD.     

Statistical parametric mapping demonstrates asymmetric uptake with Tc-99m ECD and Tc-99m HMPAO SPECT in normal brain

Tc-99m ethyl cysteinate diethylester (ECD) and Tc-99m hexamethyl propylene amine oxime (HMPAO) are commonly used for single-photon emission computed tomography (SPECT) studies of a variety of neurologic disorders. Although these tracers have been very helpful in diagnosing and guiding treatment of neurologic disease, data describing the distribution and laterality of these tracers in normal resting brain are limited. Advances in quantitative functional imaging have demonstrated the value of using resting studies from control populations as a baseline to account for physiologic fluctuations in cerebral perfusion. Here, we report results from 30 resting Tc-99m ECD SPECT scans and 14 resting Tc-99m HMPAO scans of normal volunteers with no history of neurologic disease. Scans were analyzed with regions of interest and with statistical parametric mapping, with comparisons performed laterally (left vs. right), as well as for age, gender, and handedness. The results show regions of significant asymmetry in the normal controls affecting widespread areas in the cerebral hemispheres, but most marked in superior parietotemporal region and frontal lobes. The results have important implications for the use of normal control SPECT images in the evaluation of patients with neurologic disease.     

Cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer's disease

Cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake was measured in 11 patients with dementia with Lewy bodies (DLB), 10 patients with Alzheimer's disease (AD), and 10 age matched control subjects. The severity of cognitive impairment and duration of symptoms in patients with DLB matched that in the patients with AD. The heart/mediastinum (H/M) ratio of MIBG uptake in the patients with AD was indistinguishable from that in the control subjects. However, the H/M ratio in all patients with DLB was significantly lower than that in the patients with AD and control subjects (p<0.001). These findings indicate that local myocardial sympathetic nerves are affected in DLB and that cardiac (123)I-MIBG scintigraphy may provide a means of differentiating DLB from AD.     

Association between medial temporal lobe atrophy on CT and parietotemporal uptake decrease on SPECT in Alzheimer's disease

OBJECTIVES—Alzheimer's disease is the mostfrequent cause of degenerative dementia. Despite the availablediagnostic criteria, improvement of diagnosic accuracy is stillrequired. The aim of this prospective study was to assess in a largepopulation of patients referred to a memory clinic the diagnostic valueof the combination of medial temporal lobe atrophy on temporal orientedCT and decreased temporoparietal uptake on HMPAO single photon emissiontomography (SPECT).
METHODS—The study was conducted in 125 patientsaged 51-93: 64 with probable Alzheimer's disease (Mean (SD) minimental state examination (MMSE)=18.34 (6.93)), duration of disease=6.48(2.93) years, 13possible Alzheimer's disease (MMSE=21.58 (5.48),duration of disease=6.08 (2.56)), 48 patients with miscellaneous memorydisorders (MMSE=21.98 (6.10), duration the disease = 6.85 (3.91)).
RESULTS—For the diagnosis of probableAlzheimer's disease, the sensitivity of this association was 0.56, thespecificity 0.93, the positive predictive value 0.95, and the negativepredictive value 0.45. The diagnosic accuracy was 0.68. Both medialtemporal atrophy and parietotemporal decrease in uptake were present infour of 13 patients with possible Alzheimer's disease and 11 of 48 with miscellaneous memory disorders. The association was absent in 27 of 29 patients with frontotemporal dementia. In mild stages (MMSE>18;n = 32), the sensitivity of the association was 0.34,the specificity0.93, the positive predictive value 0.85, and the negative predictivevalue 0.57. The diagnosic accuracy was 0.53.
CONCLUSION—This association, although notsensitive, helps to select patients with high probability ofAlzheimer's disease at an early stage which can be of interest forclinical and research purposes.

     

Frontal lobe tasks do not reflect frontal lobe function in patients with probable Alzheimer's disease

Thirty-one patients with probable Alzheimer's disease (AD) according to NINCDS-ADRDA criteria were psychometrically tested with various frontal lobe tasks. The results were correlated with regional cerebral glucose metabolism (rCMRG1) as measured by positron emission tomography of 18F-2-fluoro-2-deoxy-D-glucose. RCMRG1 of frontal functional-anatomically defined regions was not linked to the performance seen in frontal lobe testing. The majority of the frontal lobe tasks showed a high correlation to severity of dementia that was related to rCMRG1 of the temporo-parietal cortex. There were high intercorrelations of frontal lobe test scores to other tests. Thus, these tasks seem to measure nonspecific cognitive changes in AD patients.     

Tc-99m HMPAO brain SPECT findings in mild and moderate Alzheimer's disease: correlation with event related potentials

We investigated whether brain SPECT findings show any differences between patients with mild and moderate Alzheimer's disease (AD) and to compare results with event related potentials (ERPs). Twenty-two patients with mild to moderate AD diagnosed according to NINCDS-ADRDA criteria and 10 age-matched control subjects were included in this prospective study. All subjects underwent ERP recordings and Tc-99m HMPAO brain SPECT study. Cortical perfusion index (CPI) was calculated as the ratio of cortical activity to the cerebellum activity. CPI was found to be statistically lower in bilaterally posterolateral temporal cortex and precuneus in the moderate AD compared to the control group. There was no statistically significant difference between the mild AD and control groups for CPI in any cortical areas. The mean P300 latency was statistically prolonged in the mild and moderate AD compared to the control group. In addition, in moderate AD P300 latency was longer than in mild AD. While the mean P300 amplitude was statistically reduced in moderate AD compared to the control and mild AD, there was no statistically significant difference between the mild AD and control groups. There was a strong negative correlation between P300 latency and CPI in the right and left precuneus in the moderate AD group. The present study suggested that Tc-99m HMPAO SPECT study is the more appropriate technique for patients with moderate AD rather than mild AD. Our results indicated that alterations in ERPs, especially prolongation of P300 latency could be a finding that occurred earlier than the deterioration in cerebral blood flow. We thought that precuneus is closely related to cognitive function and may have an important role in the pathophysiology of AD.     

SPECT imaging of dopamine transporters with (99m)Tc-TRODAT-1 in major depression and Parkinson's disease

To investigate dopamine transporter in major depressive disorder and Parkinson's disease, the authors obtained single photon emission computed tomography (SPECT) brain images from 13 patients with major depression, 17 Parkinson's disease patients, and 10 healthy volunteers by using 99mTc-TRODAT-1. The authors found the 99mTc-TRODAT-1 radio signal in the striatum was reduced in the majority of patients with major depressive disorder, and this decrease was even more severe in patients with Parkinson's disease. The results support the hypothesis of dopamine hypofunction in major depressive disorder and suggest that deficient dopamine transporter may be involved in the etiology of severe major depressive disorder.     

Evaluation of SPECT with N-isopropyl [I-123]-p-iodoamphetamine (IMP) or technetium-99m [99mTc]-d,l-hexamethylpropyleneamine oxime (d, 1-HM-PAO) in cerebral concussion

123I-IMP and Tc-PAO SPECT were performed in 20 cases of cerebral concussion ranging in age from 4 to 20 years old, including six cases of the juvenile head trauma syndrome (JHTS). The SPECT findings were divided into two main types: six cases in the normal group with no blood flow abnormalities, and 14 cases in abnormal group showing reduced blood flow, mainly in cerebellum and occipital lobe except in one case. In 10 cases with reduced blood flow which could be analyzed, calculation of the blood flow ratio in the temporal and occipital lobes and the cerebellum with the frontal lobe taken as 100 showed values of 93.5% for the temporal lobe, 82.7% for the occipital lobe and 76.8% for the cerebellum. A statistically significant reduction in blood flow occurred in the occipital lobe and cerebellum. In blood examination, abnormally high values of white blood cell counts were observed transiently in 94% of cerebral concussion cases. Abnormalities in brain stem and hypothalamus appeared to cause these abnormal WBC values. From these findings, it was suggested that the blood flow regions of the basilar and posterior cerebral arteries, i.e., the brain stem and hypothalamus are closely connected with the lesions responsible for cerebral concussion. It also appeared that the JHTS occurs in cerebral concussion cases where recovery of the abnormal blood flow in these regions in poor.     

SPECT with [99mTc]-d,l-hexamethyl-propylene amine oxime (HM-PAO) compared with regional cerebral blood flow measured by PET: effects of linearization

In order to validate the use of technetium-99m-d,l-hexamethylpropyleneamine oxime (HM-PAO) as a flow tracer, a total of 21 cases were studied with single photon emission computerized tomography (SPECT), and compared to regional cerebral blood flow (rCBF) measured by position emission tomography (PET) using the oxygen-15 CO2 inhalation technique. Although HM-PAO SPECT and rCBF PET images showed a similar distribution pattern the HM-PAO SPECT image showed less contrast between high and low activity flow regions than the rCBF image and a nonlinear relationship between HM-PAO activity and rCBF was shown. Based on the assumption of flow-dependent backdiffusion of HM-PAO from the brain, we applied a "linearization algorithm" to correct the HM-PAO SPECT images. The corrected HM-PAO SPECT images revealed a good linear correlation with rCBF (r = 0.901, p less than 0.001). The results indicated HM-PAO can be used as a flow tracer with SPECT after proper correction.