Yuichi Satoh

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.

Hemodynamic aspects of Alzheimer's disease

Abstract: Neuroradiological functional imaging techniques demonstrate the patterns of hypoperfusion and hypometabolism that are thought to be useful in the differential diagnosis of Alzheimers disease (AD) from other dementing disorders. Besides the distribution patterns of perfusion or energy metabolism, vascular transit time (VTT), vascular reactivity (VR), and oxygen extraction fraction (OEF), which can be measured with positron emission tomography (PET), provide hemodynamic aspects of brain pathophysiology. In order to evaluate the hemodynamic features of AD, PET studies were carried out in 20 patients with probable AD and 20 patients with vascular dementia (VaD). The PET findings were not included in their diagnostic process of AD. Using oxygen‐15‐labeled compounds, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), OEF, cerebral blood volume, and VTT were measured quantitatively during resting state. To evaluate VR, CBF was also measured during CO2 inhalation. There was a significant increase in OEF in and around the parietotemporal cortices, but both VTT and VR were well preserved in patients with AD. By contrast, VR was markedly depressed and VTT was mildly prolonged in patients with VaD. Thus, from the hemodynamic point of view, the preservation of vascular reserve may be a distinct difference between AD and VaD. Furthermore, this indicates a hemodynamic integrity of the vasculature in the level of arterioles in AD.

Evolution of Crossed Cerebellar Diaschisis in Middle Cerebral Artery Infarction

To elucidate the evolution of crossed cerebellar diaschisis, cerebral oxygen metabolism was measured repeatedly by positron emission tomography (PET) in 35 consecutive patients with unilateral cerebral infarction within the territory of middle cerebral artery. The crossed cerebellar diaschisis was defined as significant when the laterality ratio of cerebral oxygen metabolism between the left and right cerebellar hemispheres exceeded the control range (mean ± 2 standard deviations) as derived from 27 age‐matched normal volunteers. Significant crossed cerebellar diaschisis was observed in 31 patients (89%) on the initial PET studies. Of these 31 patients, 23 with infarcts involving the frontal sensorimotor cortex persistently had crossed cerebellar diaschisis up to 5 years after onset, whereas the diaschisis disappeared in 8 patients with smaller infarcts mainly in the frontal or parietal lobe without recovery of oxygen metabolism in the infarcted areas. These present results suggest that crossed cerebellar diaschisis can exist persistently even in the late stage in those having a lesion involving the cortical pontine‐cerebellar pathways.

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.

Cerebrovascular lesions in elderly Japanese patients with Alzheimer's disease

OBJECTIVE Cerebrovascular lesions (CVLs) are known to play important roles in the pathophysiology underlying Alzheimers disease (AD), especially in elderly AD cases. The present study was conducted to elucidate the relationship between the CVLs and vascular risk factors (VRFs) in elderly Japanese patients with AD. SUBJECTS AND METHODS The CVLs such as lacunar infarcts, old microbleeds (OMBs), white matter lesions (WMLs), and occlusive vascular lesions on MRI were analyzed in relation to the risk factors in 120 Japanese patients with probable AD. Their mean age was 75.6 years. The subjects were divided into two age groups: young-old group (YOG) consisting of 55 cases being younger than 75 years and old-old group (OOG) consisting of 65 cases being 75 years or older. RESULTS In overall analysis, 10 cases (8.3%) showed brain atrophy without CVLs on MRI, 46 cases (38.3%) showed WMLs in addition to the brain atrophy, 61 cases (50.8%) showed lacunar lesions, and 3 cases (2.5%) were diagnosed as having a superficial siderosis. Lacunar infarcts and OMBs were more frequently observed in OOG than in YOG, and were also more frequently observed in those with 2 or more VRFs than those with less than 2 VRFs (p<0.05). The WMLs were more pronounced in OOG, and in those with more VRFs. CONCLUSION The CVLs including lacunes, WMLs, and OMBs were present more than 90% of elderly Japanese patients with AD. As the severity of CVLs was associated with VRFs and age, VRFs may modify clinical presentation of elderly AD patients.

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.

High Prevalence of Gastroesophageal Reflux Disease in Parkinson’s Disease: A Questionnaire-Based Study

The aim of this study is to investigate the frequency and clinical features of gastroesophageal reflex disease (GERD) in Parkinsons disease (PD). Consecutively recruited PD patients and controls were questioned about heartburn and GERD with a questionnaire. In PD patients, disease duration and severity, quality of life, and nonmotor symptoms were also examined and then the clinical features of GERD were analyzed. A total of 102 patients and 49 controls were enrolled and 21 patients and 4 controls had heartburn, significantly frequent in PD. The prevalence rate of GERD was 26.5% in PD and the odds ratio was 4.05. Heartburn, bent forward flexion, and wearing-off phenomenon were frequent, and scores of UPDRS, total and part II, PD questionnaire-39, and nonmotor symptom scale were significantly higher in PD patients with GERD than without GERD. Multiple logistic regression analysis revealed statistical significance in UPDRS part II and nonmotor symptom scale. This study suggests that GERD is prevalent in PD. Deterioration of daily living activities and other nonmotor symptoms can imply the presence of GERD. Because clinical symptoms of GERD are usually treatable, the management can improve the patients quality of life. Increased attention should be given to detect GERD in PD.

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.