Preclinical evidence of Alzheimer changes in progressive mild cognitive impairment: a qualitative and quantitative SPECT study.

OBJECTIVES: Baseline brain single-photon emission computed tomography (SPECT) can predict mild cognitive impairment (MCI) patients at risk for progressive MCI (PMCI). METHODS: Twenty-eight subjects [12 MCI, 6 with probable Alzheimer's Disease (AD), and 10 normal subjects] underwent baseline brain SPECT and were clinically followed for a mean period of 36 months. RESULTS: Of 12 MCI patients, 6 progressed to PMCI and 6 remained stable. Baseline SPECT identified asymmetric perfusion reduction in the parahippocampus (-5%), lateral parietal (-8%), and posterior cingulate (-11%) cortices--reductions consistent with that of mild AD--in five of the six PMCI patients. Significant perfusion reduction was observed particularly in the frontal cortices of probable AD when compared with PMCI (P < 0.05). CONCLUSION: Baseline SPECT can identify brain perfusion abnormalities among patients with MCI for progression to PMCI. This imaging modality may aid in MCI treatment stratification.

Function of sigma1 receptors in Parkinson's disease.

OBJECTIVE: The objective of this study was to investigate the mapping of sigma1 receptors in Parkinson's disease (PD) using [11C]SA4503 and positron emission tomography (PET), and to assess whether sigma1 receptors are involved in the damaged dopaminergic system in PD patients. MATERIALS AND METHODS: We studied seven normal volunteers and six PD patients. The low density of dopamine transporters and the normal or high density of dopamine receptors were confirmed in the putamen of all patients using [11C]CFT and [11C]RAC PET. A dynamic series of PET data acquisition was performed with arterial blood sampling. We computed the binding potential (BP) of [11C]SA4503. RESULTS: In PD patients, the BP was significantly lower on the more affected than the less affected side of the anterior putamen, although there was no significant difference with respect to the BP between patients and controls. CONCLUSIONS: Release of dopamine is reduced asymmetrically in the putamen of early PD. [11C]SA4503 PET is an indicator of presynaptic dopaminergic damage in PD.

Benzodiazepine receptor imaging with iomazenil SPECT in aphasic patients with cerebral infarction.

To investigate the relationship between prognosis of aphasia and neuronal damage in the cerebral cortex, we evaluated the distribution of central-type benzodiazepine receptor (BZR) binding in post-stroke aphasics with [123I]iomazenil and SPECT. We performed iomazenil SPECT in six aphasic patients (aged from 45 to 75 years; all right-handed) with unilateral left cerebral infarction. Three patients showed signs of Broca's aphasia and the other three Wernicke's aphasia. Cerebral blood flow (CBF) imaging was performed with [123I]iodoamphetamine (IMP). The regions of interest (ROIs) on both images were set in the cerebral cortex, cerebellar cortex and language-relevant area in both hemispheres. Three patients were classified in the mild prognosis group and the other three in the moderate prognosis group. The left language-relevant area was more closely concerned with the difference in aphasic symptoms than the right one in both BZR and CBF distribution, but the ipsilateral to the contralateral ratio (I/C ratio) in the language-relevant areas in the BZR distribution was significantly lower in the moderate prognosis group than in the mild prognosis group, although no difference was seen for these values between the two groups in the CBF distribution. These results suggest that BZR imaging, which makes possible an increase in neuronal cell viability in the cerebral cortex, is useful not only for clarifying the aphasic symptoms but also for evaluating the prognosis of aphasia in patients with cerebral infarction.

[A quantitative study of regional cerebral blood flow in patients with dementia of Alzheimer type using single photon emission computed tomography--clinical application of the IMP autoradiographic method (IMP ARG method)].

We quantitatively measured regional cerebral blood flow (rCBF) in 37 patients with dementia of Alzheimer type (DAT) to investigate the clinical utilities of the N-isopropyl-p-[123I]iodoamphetamine autoradiographic method (IMP ARG method) that is a quantitative method more simplified and less invasive for IMP-SPECT developed by Iida et al. A given standard input function and a given value of distribution volume (Vd) used for the rCBF measurement of this method were calculated from the dynamic study by six normal volunteers. Mean values [SD] of rCBF (ml/ 100 g/min) in the Cerebral Cortex were 49.0 [6.0] in the controls (n = 20), 42.6 [5.9] in mild DAT group (n = 14), 36.7 [5.5] in moderate DAT group (n = 12), and 26.4 [7.5] in severe DAT group (n = 11), respectively. These values were significantly different between each neighboring group. Moreover, the correlations between the score by the Hasegawa dementia scale (HDS-R) and each rCBF were significant in the temporal, parietal, and frontal cortex. These findings suggest that the rCBF measurement in IMP-SPECT using this method is useful for the diagnosis of the clinical severity in patients with DAT.

[Benzodiazepine receptor and cerebral blood flow in early Alzheimer's disease--SPECT study using 123I-iomazenil and 123I-IMP].

This study was designed to investigate benzodiazepine receptors (BZR) and cerebral blood flow (CBF) in patients with early Alzheimer's disease. Imaging of BZR and measurement of CBF were performed by SPECT using 123I-Iomazenil (IMZ) and 123I-IMP respectively, in seven patients with early Alzheimer's disease and five patients with unilateral left cerebral infarction as controls. The values for the normal cerebral hemisphere (ratio to the contralateral cerebellum) in patients with cerebral infarction were adopted as control values. In patients with Alzheimer's disease, the CBF (ratio to cerebellum) decreased significantly in the frontal cortex and the parietal cortex compared with the control values. There was no significant difference in late IMZ SPECT counts (ratio to cerebellum) and washout (the ratio of late-to-early IMZ SPECT counts) between patients with Alzheimer's disease and the controls. However, the late IMZ SPECT counts and washout decreased in one patient with moderate dementia. There was a significant correlation between the severity of dementia and the late IMZ SPECT counts in the temporal cortex and the parietal cortex. These results suggest that benzodiazepine binding sites are relatively well preserved in patients with early Alzheimer's disease, and reduction of the CBF is caused by neuronal dysfunction rather than by neuronal loss. IMZ SPECT study is useful and necessary for clarifying the pathophysiological state in Alzheimer's disease.

[Cerebello-cerebral functional relationship in spinocerebellar degeneration using positron emission tomography].

In order to investigate the laterality of cerebellar ataxia and its influence for the cerebral cortex in spinocerebellar degeneration (SCD), regional cerebral blood flow (r CBF) was measured using positron emission tomography (PET) in 10 patients with sporadic olivopontocerebellar atrophy (sOPCA), 7 patients with hereditary SCD (h SCD), and 10 age matched control subjects. The laterality of cerebellar ataxia was evaluated by the total score of the difference between left and right limbs of three limb-coordination tests. The lateralities of rCBF were calculated by asymmetry indices (AIs) of each region of interest in the cerebellum, thalamus, caudate, putamen, cerebral cortices. The laterality of cerebellar ataxia was significantly correlated with AI in the cerebellum in patients with sOPCA. Furthermore, significant negative correlations were observed between AI in the cerebellum and each AI in the thalamus, frontal cortex in patients with sOPCA. However, no correlations were observed between AI in the cerebellum and the other AIs in controls and patients with h SCD. Duration of illness in patients with sOPCA with laterality is shorter than that in patients without laterality. These results suggest that the existence of crossed cerebello-cerebral diaschisis (CCCD) resulting from transneuronal deactivation through cerebello-thalamo-cerebral pathway in patients with the early stage of sOPCA with laterality.

[A case of motor neuron disease with dementia--cerebral blood flow and cerebral oxygen metabolism].

A 51-year-old man developed muscle weakness of the bilateral upper extremities, and mental changes beginning with personality change. There was no history of mental illness in his family. A neurological examination 1 year after the onset revealed muscle atrophy and fasciculation of his bilateral upper extremities Neuropsychological examination revealed concrete speech, paraphasia, and lack of judgment. Disorientation, amnesia, dyscalculia, and spatial agnosia, however, were not recognized. These neuropsychological findings were compatible with dementia of frontal lobe type. EMG and muscle biopsy revealed neurogenic muscular atrophy. There was no abnormal findings in the brain X-CT and the brain MRI. PET study using C15O2 and 15O2 revealed reduction of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in the bilateral medial frontal cortex, the left temporal cortex and the bilateral thalamus. From these these findings the patient was diagnosed as having motor neuron disease with dementia. Muscle atrophy and dementia worsened gradually. A second PET study 2 years and 6 months after the onset revealed severe reduction of CBF and CMRO2 in the bilateral temporal cortex and the thalamus. These PET findings suggested that dysfunction of the temporal cortex and the thalamus related to dementia in this case.