Eriko Yokoyama

Can PET Data Differentiate Alzheimer's Disease from Vascular Dementia?

Abstract: The present study endeavored to differentiate Alzheimers disease (AD) from vascular dementia (VaD) by comparing the metabolic and hemodynamic parameters. Positron emission tomographic (PET) studies were carried out in 13 patients with probable AD and 20 patients with VaD. PET findings were not included in the diagnostic criteria of AD or VaD. Using oxygen‐15 labeled compounds, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), cerebral blood volume, and vascular transit time (VTT) were measured quantitatively during the resting state. To evaluate vascular reactivity (VR), CBF was also measured during 7% CO2 inhalation. Regional CBF from the parietal cortex positively correlated with the neuropsychological scores in both AD and VaD groups. The typical parietotemporal pattern of hypoperfusion and hypometabolism was observed in the AD group, whereas the frontal lobe including the cingulate and superior frontal gyri were predominantly affected in the VaD group. The occipital cortex was preserved in both groups. A significant increase of the OEF was found in the parietotemporal areas in the AD group. No significant prolongation was seen with VTT. There was a marked difference in VR between the two groups: VR was depleted in the VaD group, whereas VR was normal in the AD group. The increased OEF with preserved vascular reserve seen in AD may implicate participation of a vascular factor in the pathogenesis of AD, possibly at the capillary level. Thus, PET provides important functional information in discriminating AD from VaD by comparing the patterns of hypoperfusion and/or hypometabolism, and in the understanding of the underlying hemodynamic pathophysiology.

Age-related decline of cerebral oxygen metabolism in normal population detected with positron emission tomography

Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured in 32 healthy volunteers aged from 27 to 67 years. In bilateral putamen, left supratemporal, left infrafrontal and left parietal cortices, CMRO2 showed a significant decline during aging. The age-related decline of CBF was seen only at the left superior temporal cortex. The mean CMRO2 was significantly lower in the elder group (over 51 years old) than in the younger group (under 50 years old), whereas no significant difference in mean CBF between the two groups. The poor correlation of CBF to the age could be explained partly by the fact that CBF is easily influenced by the physiological, psychological and/or environmental factors. The age-related changes of CMRO2 were more marked in the association cortices of the left hemisphere than in that of the right hemisphere.

Effects of yokukansan on behavioral and psychological symptoms of vascular dementia: An open-label trial

Previous clinical trials suggest that the traditional Japanese medicine yokukansan has beneficial effects on the behavioral and psychological symptoms of dementia (BPSD). The present study was conducted to elucidate the efficacy of yokukansan on BPSD in patients with vascular dementia. Thirteen Japanese patients (9 men and 4 women) who were diagnosed as having vascular dementia (VaD) according to the diagnostic criteria of NINDS-AIREN were subjected to the open-label clinical trial in which yokukansan (7.5g/day) has been given for 4 weeks. Their mean age was 71.2±6.5 years. The BPSD was evaluated using the Neuropsychiatric Inventory (NPI), cognitive function was evaluated by the Mini-Mental State Examination (MMSE), the activities of daily living was evaluated by Barthel index (BI) and Disability Assessment for Dementia (DAD), and the extrapyramidal signs were evaluated by United Parkinsons Disease Rating Scale (UPDRS). The mean NPI was 33.0±17.3 and 23.6±13.9 for the baseline and after treatment, respectively. It was significantly improved after treatment (p<0.05). In the NPI-subcategories, there was a significant improvement in agitation and disinhibition after the treatment. There was no significant change in MMSE, BI, DAD or UPDRS before and after the treatment. There was no adverse effect during the treatment period. The present results suggest that yokukansan is beneficial for the treatment of BPSD in VaD patients.

Vascular and metabolic reserve in Alzheimer’s disease

Vascular and metabolic reserve were analyzed in probable Alzheimers disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.

Effects of fasudil hydrochloride on cerebral blood flow in patients with chronic cerebral infarction

Summary: To evaluate the effect of the novel intracellular calcium antagonist fasudil hydrochloride, cerebral blood flow (CBF) was measured quantitatively with positron emission tomography following the intravenous administration of fasudil in five patients with chronic cerebral infarction. The hemispheric mean CBF increased significantly on both hemispheres 30, 60, and 90 min after the administration of fasudil when the CBF values were corrected according to Paco2 level, although there was no significant change in raw CBF data. A significant increase of CBF was seen in the cerebellar hemisphere and thalamus at 30 min and in the occipital cortex at 90 min. There was no significant fall in the systemic blood pressure after the administration of fasudil.

Correlation of EEG activities between slow-wave sleep and wakefulness in patients with supra-tentorial stroke

SummaryUsing topographic EEG mapping, we studied the relationships between delta activity during slow-wave sleep (SWS) and the background EEG activity during wakefulness, in 11 normal subjects and 35 stroke patients with unilateral supra-tentorial lesions. Delta-1 power during SWS showed a significant positive correlation with alpha-1 power during wakefulness, in both hemispheres. Delta-1 and delta-2 power during SWS correlated positively not only with alpha-2 power, but also with delta-1 and delta-2 power during wakefulness in the affected hemisphere. These figures indicate that the amount of delta activity during SWS can be associated with that of alpha activity during wakefulness. A close negative correlation was observed between delta power during SWS and the age of the subjects in the patient group. The Barthel index showed no significant correlation with delta-1 or delta-2 power in either hemisphere in patient group. Our results suggest that delta activity during SWS may be associated with dysfunction of the cerebral cortex in stroke patients as well as in normal aged subjects.

Verb Generation in Japanese—A Multicenter PET Activation Study

Cerebral blood flow (CBF) during silent verb generation was measured at four Japanese PET centers. To minimize the variance of the measurement, speakers of a single language (Japanese) served as subjects and experimental conditions at the four PET centers were controlled as much as possible. Two types of activation patterns were observed: activations in the left dorsolateral prefrontal cortices and the medial frontal cortex (at the two centers with a 2D PET scanner) and additional activation in the left posterior temporal cortex (at the two centers with a 3D scanner). This suggests either a difference in the sensitivity of the two types of PET scanners (viz., a 3D scanner is generally more sensitive than a 2D scanner) and/or subject bias due to the small number of subjects at the individual centers. The pooled activation pattern was fundamentally similar to activation patterns obtained in the previous studies for verb generation in English and other European languages, suggesting that regions for verb generation are independent of particular languages. Regions relevant to verb generation are discussed.

Acute Effects of Cigarette Smoking on Global Cerebral Blood Flow in Overnight Abstinent Tobacco Smokers

The acute effects of tobacco smoking on gCBF were studied.

Infratentorial infarction: Correlation of MR findings with neurological and angiographical features

Using magnetic resonance imaging, we reviewed 141 infratentorial infarcts in 81 consecutive cases: 65 infarcts were seen in the paramedian pons, while 18 in the posterior inferior cerebellar artery (PICA) territory and 17 in the watershed area between PICA and superior cerebellar artery. No comparable sign or symptom was observed for 44 (31.2%) infarcts, whereas 66 (46.8%) infarcts appeared symptomatic and 31 (22.0%) infarcts were regarded as equivocal mainly due to the coexisting supratentorial lesions or non-localizing symptoms. The frequent coexistence of basal ganglionic small infarcts in those with infratentorial small (< 15 mm) infarcts implicated their common pathogenetic background. The fact that atrial fibrillation was seen in 33.3% of those with large (> 15 mm) infarcts whereas it was seen in only 6.5% of those with small infarcts may suggest a cardiogenic embolism as a possible cause of infratentorial large infarcts. Major artery occlusive lesion was seen in 15 of 22 cases with cerebellar infarction, whereas no occlusive lesion was seen in the majority of cases with pontine small infarcts. With MR imaging, infratentorial infarcts were detected more frequently than in the previous studies based on X-ray CT, and they can be considered as a benign condition.

Regional brain activity during face and word discrimination: simultaneous recording of event‐related potentials and positron emission tomography

In order to clarify the brain mechanisms involved in the recognition of faces, words, and figures, spatiotemporal analyses were carried out with event-related potentials (ERPs) and positron emission tomography (PET) in normal subjects. In the first experiment, we analyzed the ERPs of eight normal subjects under a passive habituation paradigm using pictures of faces and letters. In the second experiment, regional cerebral blood flow (rCBF) measured using PET was obtained simultaneously with the ERP recordings during a continuous performance task (CPT) in 12 normal subjects. This required the active discrimination of famous peoples faces, meaningful words consisting of two Japanese hiragana characters, and simple geometric figures. There were similar deflections in the global field power (GFP) in the first 200 ms of the passive and active tasks, regardless of type of stimuli. This suggests a common time course in the visual information processing mechanisms during the preattentive stage. Mesiotemporal activity, dominant on the right, was seen during the face discrimination task in both the PET results and the ERP topographies. In the word task, activity that was clearly dominant on the left was observed at around a 160 ms latency in the posteriotemporal region of the ERP topography and this again coincided well with the PET data. The spatiotemporal resolution of the analyses was improved by combining PET and topographic ERP studies, and this provided additional neurophysiological information concerning cognitive processing.