Hidehiko Nabatame

Cerebral Correlates of the Progression Rate of the Cognitive Decline in Probable Alzheimer’s Disease

Objective: To evaluate the possible relation between the rate of cognitive deterioration in patients with probable Alzheimer’s disease (AD) and the distribution pattern of neural dysfunction. Methods: The regional cerebral blood flow (rCBF) was measured in rapidly and slowly progressing groups of AD patients using single-photon emission computed tomography and was compared between the groups. While controlling for demographic and clinical factors that could be associated with the stage and prognosis of the illness, the deterioration rate of the Mini Mental State Examination (MMSE) score was significantly greater in the rapidly progressing group than that in the slowly progressing group. Results: The rCBF in the right posterodorsal, anterior and superior prefrontal cortices and the inferior parietal cortex was significantly lower in the rapidly progressing patients. Moreover, lower perfusion in these regions correlated significantly with rapid deterioration in the MMSE. Conclusions: These findings suggest that the rCBF values in these cortical regions could be useful in predicting which AD patients will show a relatively rapid cognitive decline.

Factor Structure of a Modified Version of the Wisconsin Card Sorting Test: An Analysis of Executive Deficit in Alzheimer’s Disease and Mild Cognitive Impairment

In order to explore the factor structure of a modified version of the Wisconsin Card Sorting Test (mWCST) and to identify the dimensions of deficit in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), conventional mWCST scores in 55 AD patients, 17 MCI patients, and 22 controls were subjected to factor analysis. Three factors, perseveration, inefficient sorting, and nonperseverative error, were obtained. Perseveration score was significantly poorer in both AD and MCI than in controls. By contrast, the MCI group showed significantly poorer scores on the nonperseverative error factor than did the AD patients, and the controls yielded intermediate values between the two patient groups. The perseveration factor was significantly correlated with the other estimates of executive function. This study suggested that the many mWCST scores could be reduced to three major factors, and that the perseveration score may effectively represent an aspect of executive dysfunction in AD and MCI patients.

Assessment of Benzodiazepine Receptors Using Iodine-123–Labeled Iomazenil Single-Photon Emission Computed Tomography in Patients With Ischemic Cerebrovascular Disease A Comparison With PET Study

BACKGROUND AND PURPOSE [123I]Iomazenil (IMZ) is a tracer used for single-photon emission computed tomography (SPECT) that has the characteristics of selectively binding to central benzodiazepine receptors (BZR) in the neuron membrane. To determine whether IMZ SPECT provides new information on assessing neuronal damage after ischemic insult to the brain, we compared IMZ SPECT images with the cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral metabolic rate of glucose (CMRGlc) studied by position emission tomography in the chronic stage of ischemic stroke. METHODS Five patients (male; mean age, 63.2 +/- 6.0 years) with ischemic cerebrovascular disease and 6 age- and sex-matched normal control subjects were studied. IMZ images obtained 180 minutes after injection were analyzed for BZR binding, and these images were compared with the CBF, CMRO2, and CMRGlc obtained by position emission tomography in the same perfusion areas both visually and quantitatively. RESULTS In the visual analysis of data obtained from 4 patients with subcortical infarction, decreased IMZ accumulation was observed locally in the overlying normal-appearing cortices of the affected hemisphere, where extensive hypoperfusion and hypometabolism were seen on the images of CBF, CMRO2, and CMRGlc. The regional relative IMZ uptake (regional to cerebellar ratio) for all 5 patients was significantly correlated with the corresponding regional CMRO2 values (r = .45, P < .05). However, no significant correlation was found of the IMZ uptake with either the regional CBF or the regional CMRGlc. CONCLUSIONS The use of IMZ SPECT provides new information on the neuronal alteration induced by chronic ischemic cerebrovascular disease.

Regional Cerebral Blood Flow Abnormalities in Nondemented Patients With Memory Impairment

Background. Patients with objective evidence of memory impairment have been considered to be at risk for developing Alzheimers disease (AD). However, little is known about patterns of regional cerebral blood flow abnormalities and their prognostic significance in these patients. Methods. The authors retrospectively studied 28 nondemented subjects with memory loss and investigated patterns of blood flow abnormalities on single photon emission computed tomography (SPECT). Results. The patients were followed up for more than 2 years; during follow‐up, 14 patients (50%) developed AD. The onset of memory impairment in patients who progressed to AD was significantly earlier than in those who remained in a nondemented condition. SPECT data from the initial evaluation were analyzed by region of interest analysis and statistical parametric mapping. Interestingly, both groups of patients shared hypoperfusion in the medial temporal regions and the posterior cingulate. In addition to these regions, significant blood flow reduction in the parietal and anterior cingulate cortices was detected in patients who progressed to AD. Conclusions. These results demonstrate that (1) subjects with an earlier onset of memory loss have an increased risk for developing AD, (2) SPECT can be useful for distinguishing subjects with memory loss who will rapidly progress to AD from those who will not, and (3) perfusion impairment typical of AD was evident even in subjects with memory impairment who remained nondemented.

Spinocerebellar Degeneration: Qualitative and Quantitative MR Analysis of Atrophy

Magnetic resonance imaging at 1.5 T was performed in 27 patients with either the cerebellar or spinocerebellar form of spinocerebellar degeneration and in 10 control subjects. Neither T1- nor T2-weighted images (T1WIs and T2WIs) of the patients showed any abnormal intensity areas within the cerebellum or in any other structures of the brain. The T2WIs delineated normal configurations of symmetrical dentate and red nuclei. On T1WIs two patterns of atrophy were detected: (a) moderate to severe shrinkage of the basis pontis and the middle cerebellar peduncles associated with atrophy of the cerebellum, and (b) moderate atrophy of the cerebellum with a preserved basis pontis. The former morphological changes are consistent with the pathology of pontocerebellar atrophy (PCA) and the latter with those of cerebellar cortical degeneration (CCD). In 11 patients, only after a quantitative analysis of the images were we able to classify them in one of the two morphological categories (PCA or CCD). There was a significant correlation between atrophy of the cerebellum and atrophy of the basis pontis. Furthermore, in the PCA group the anterior portion of the body of the corpus callosum was significantly smaller in comparison with the control subjects.

Decreased cerebral blood flow and prognosis of Alzheimer's disease: a multicenter HMPAO-SPECT study.

Purpose: To determine the usefulness of brain perfusion SPECT for evaluating the severity and progression of Alzheimers disease (AD).Methods: Eighty-four AD patients were included. At entry,99mTc-HMPAO-SPECT, the Mini Mental State Examination (MMSE), Mental Function Impairment Scale (MENFIS), and the Raven Colored Progression Matrix (RCPM) were performed for all 84 patients. During the follow-up periods, two individual MMSE evaluations in 34 patients, two MENFIS evaluations in 30 patients, and two RCPM evaluations in 20 patients were performed. Based on the regions of decreased cerebral blood flow demonstrated on 3D-SSP images of SPECT, the cases were classified as type A (no decrease), type B (decreased blood flow in the parietal or temporal lobe), type C (decreased blood flow in the frontal lobe and parietal or temporal lobe), type Pc (decreased blood flow in posterior cingulate gyrus only), and “other types”. The types of decreased blood flow, scores on neuropsychological evaluations, and symptom progression were analyzed.Results: The MENFIS, MMSE, and RCPM scores were poorest in type C patients at entry. The degree of decrease of these scores during the follow-up periods was also greatest in type C. The greatest difference between patients with and without rapid progression in SPECT data of the mild AD patients (MMSE score ≥ 24) was in the frontal lobe.Conclusion: Decreased blood flow in the frontal lobe of AD patients is correlated not only with reduced cognitive function at the time of the evaluation but with rapid progression in the subsequent clinical course.

Neural Correlates of Impaired Performance on the Clock Drawing Test in Alzheimer’s Disease

To identify the neural correlates for impaired performance on the clock drawing test (CDT) in patients with Alzheimer’s disease (AD), we examined the relationship between the CDT performances and the regional cerebral blood flow (rCBF) in 100 AD patients. The patients were equally divided into a mildly impaired CDT group, a severely impaired CDT group, and two normal CDT groups, with age and dementia severity matched. Between-group comparisons revealed that rCBF reduction in the posterolateral region of the left temporal lobe was consistently associated with mild to severe impairment of the CDT in AD. Correlation analysis also showed that the rCBF in the left posterolateral temporal cortex was linearly correlated with CDT performance. The CDT scores in AD were significantly improved for the copy condition relative to the drawing-to-command condition. These findings suggest that CDT performance has a close relationship with the left posterior temporal function, and that semantic memory deficit may at least partly contribute to impaired CDT performance in AD.

Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis.

Background and Purpose Decreased cerebral blood flow with an increased oxygen extraction fraction, the so-called misery perfusion syndrome, suggests a vulnerability to reduction in cerebral perfusion pressure and a tendency to develop cerebral infarction. It is uncertain, however, whether the infarct would occur in the brain region specifically exhibiting this condition. Case Description We report the case of a patient with right intracranial internal carotid artery stenosis who presented with mild left hemiparesis resulting from a right frontal watershed infarct. Positron emission tomography 2 months after the stroke showed decreased cerebral blood flow with an increased oxygen extraction fraction in noninfarcted areas of the affected hemisphere. Maximal changes were detected in the watershed area between the middle cerebral artery and the posterior cerebral artery. Three months later, while on antiplatelet therapy, he suffered a new infarct in the right temporo-occipital watershed area that had shown the highest oxygen extraction fraction value on the first positron emission tomographic study. One month after the recurrence of stroke, a second study showed that low perfusion with increased oxygen extraction fraction persisted in the affected hemisphere to a lesser degree than in the first study. Conclusions This observation suggests that the area of low perfusion exhibiting the highest oxygen extraction fraction has the highest risk for infarction. Increased oxygen extraction fraction may be an important factor in the development of hemodynamic infarction.

Magnetic resonance images of neuro‐Behçet syndrome show precise brain stem lesions. Report of a case

ABSTRACT— Neuro‐Behcet syndrome was investigated with magnetic resonance imaging (MRI) showing precise images of brain stem lesions, and therefore suggesting the clinical usefulness of MRI in diagnosis of neuro‐Behçet syndrome.

High intensity areas on noncontrast T1-weighted MR images in cerebral infarction.

Among 46 noncontrast magnetic resonance studies on patients with cerebral infarction, 11 showed areas of high signal intensity of the involved brain on T1-weighted images. These areas were more frequent in cerebral or cerebellar cortical lesions. Lacunar infarcts in lenticular nuclei, internal capsules, corona radiata, or brain stem did not show any high signal intensity areas on T1-weighted images, whereas the thalamic infarcts did. Sequential studies revealed that these lesions displayed low signal intensity on T2-weighted images at first, and then a high signal intensity area appeared on T1-weighted images. This latter intensity gradually subsided and was replaced by a low intensity area on T2-weighted images. We suggest that these high signal intensity areas on the T1-weighted images in cerebral infarction are caused by hemorrhagic changes at the periphery of the infarction, where blood flow is restored by recanalization or collateral supply.