Hisao Tachibana

Apathy and Depression in Parkinson Disease

The purpose of this study was to investigate the prevalence and clinical correlates of apathy and depression in Parkinson disease (PD), and to clarify whether apathy can be dissociated from depression. One hundred fifty patients with PD completed the Beck Depression Inventory Second Edition (BDI-II), Starkstein’s Apathy Scale (AS), and a quality of life (QOL) battery. Hoehn and Yahr (HY) staging, the Unified Parkinson’s Disease Rating Scale (UPDRS), and the Mini-Mental State Examination (MMSE) were performed on the same day. Apathy (AS score ≥ 16) was diagnosed in 60% of patients and depression (BDI-II score ≥ 14) in 56%. Apathy coexisted with depression in 43% of patients, compared with depression without apathy in 13% and apathy without depression in 17%. Apathy scale score was significantly correlated with UPDRS scores, HY stage, and age, whereas BDI-II score was correlated only with UPDRS scores. Both AS and BDI-II scores were negatively correlated with QOL. However, multiple regression analysis revealed that depression was strongly and negatively associated with emotional well-being and communication, whereas apathy was mainly associated with cognition and stigma. These findings suggest that apathy and depression may be separable in PD, although both are common in patients with PD and are associated with QOL.

Parkinsonism after acute cadmium poisoning

A 64-year-old man suffered from acute exposure to cadmium, followed by multiple organ failure. Three months after exposure, the patient developed parkinsonian features. The case suggests that cadmium intoxication may damage the basal ganglia, resulting in parkinsonism.

Actively and passively evoked P3 latency of event-related potentials in Parkinson's disease

Event-related potentials (ERPs) generated during the performance of visual discrimination tasks were studied in 31 patients with Parkinsons disease, 9 patients with Alzheimers disease, and 37 normal control subjects. Actively and passively evoked P3 components (P3b and P3a) were respectively identified as the components of the P3 response to infrequent target stimuli and infrequent non-target stimuli. Both the P3a and P3b latencies were significantly prolonged by normal aging. Nine of the Parkinsons disease patients showed a P3b latency above the 95% confidence limit of the age-adjusted regression line based on the normal controls, while only on patient had a prolonged P3a latency. In 6 patients with demented Parkinsons disease, the P3b latency was significantly longer than in 15 age-equivalent normal subjects, although no significant difference was found in the P3a latency. On the other hand, patients with Alzheimers disease showed significant prolongation of both the P3a and P3b latencies compared to the normal controls. Furthermore, there was a significant difference in P3a latency between patients with demented Parkinsons disease and those with Alzheimers disease. These results suggest that the automatic processing stage associated with P3a may be less impaired than the attention-controlled processing reflected by P3b in patients with Parkinsons disease, and also indicate that there may be some differences in the changes of cognitive processing caused by Parkinsons disease and Alzheimers disease.

Twelve-Month Follow-Up Study of Regional Cerebral Blood Flow in Parkinson's Disease

Measurement of regional cerebral blood flow (rCBF) in 30 patients with Parkinsons disease using single-photon emission computed tomography and 123I-IMP demonstrated that hypoperfusion was relatively severer in the parietal cortex than other cortices before and after a 1-year follow-up period. The decline in the scores of the Mini-Mental State Examination was significantly correlated with the decrease in rCBF in the parietal cortex during the follow-up period. Our findings suggest that the parietal cortex is involved in the cognitive impairment in patients with Parkinsons disease.

Cerebral blood flow in Parkinson's disease, dementia with Lewy bodies, and alzheimer's disease according to three-dimensional stereotactic surface projection imaging

Regional brain perfusion was analyzed using single-photon emission computed tomography with three-dimensional stereotactic surface projections (3D-SSP) in 69 patients with Parkinson’s disease (PD), 16 patients with dementia with Lewy bodies (DLB) and 15 patients with Alzheimer’s disease (AD), and compared with that in 24 age-equivalent normal subjects. Nondemented PD patients revealed less parietal and frontal flow than controls. With mental impairment, flow reduction extended to other areas including occipital regions. PD with dementia and DLB showed similar reduction patterns, although frontal flow showed a greater reduction in DLB. AD showed little occipital reduction, but a severe parieto-temporal reduction. Thus, 3D-SSP appears to be useful in the detection of cortical lesions and the differential diagnosis of patients with cognitive impairment.

Electrophysiological analysis of cognitive slowing in Parkinson's disease

To analyze chronometrically the evidence for possible cognitive slowing in Parkinsons disease, we measured visual event-related potentials (ERPs) and reaction times (RTs) in 29 patients with nondemented Parkinsons disease and 19 age-equivalent normal controls during the performance of semantic discrimination tasks. The components of the N1, P2, NA, N2 and P3 and simple and GO/NOGO RTs were observed. The N2 was measured from difference waveforms, subtracting the ERPs to frequent stimuli from those to infrequent stimuli in the discrimination task. Difference waveforms were also derived to delineate NA by subtracting the ERPs in the simple RT task from those of the frequent stimuli of the discrimination task. The N2 and P3 latencies and GO/NOGO RT in patients with Parkinsons disease were significantly longer than those in the controls, although there were no differences in N1, P2 and NA latencies or simple RT between the two groups. The results are interpreted as electrophysiological signs of cognitive slowing, particularly with respect to stimulus classification and attention processes in Parkinsons disease, independent of sensory problems. As for the automatic/controlled processes, the present results suggest that the automatic processing stage associated with NA may be less impaired than the attention-controlled processing reflected by N2 in patients with Parkinsons disease.

Slowly progressive limb-kinetic apraxia with a decrease in unilateral cerebral blood flow.

We report two patients with slowly progressive motor disorders, whose principal manifestations were asymmetric limb‐kinetic apraxia and muscle rigidity. In both patients MRI revealed no responsible lesion, whereas single photon emission computed tomography (SPECT) showed a decrease in cerebral blood flow (CBF) in the unilateral hemisphere. One patient with mainly right‐sided apraxia had a decreased CBF in the left central region between the frontal and parietal cortices, and the other patient with left‐sided apraxia in the right parietal cortex. In agreement with asymmetric clinical symptoms, the regional CBF decrease in the unilateral cortical areas including the frontal and parietal cortices may suggest a degenerative disease, presumably diagnosed as having corticobasal degeneration.

P300 and Reaction Time in Parkinson's Disease

The event-related potential and motor reaction time were simultaneously recorded in 35 patients with Parkinsons disease (26 nondemented and nine demented) and 15 age-matched neurologically normal control subjects during the performance of visual discrimination tasks. There were no significant differences in either the latency or amplitude of the P300 component between the nondemented patients and the control subjects, but the patients with nondemented Parkinsons disease had a significantly prolonged reaction time compared with the controls. In patients with demented Parkinsons disease, both P300 latency and reaction time were significantly prolonged compared with the normal controls. These results suggest that response selection and execution are impaired in patients with nondemented Parkinsons disease, although the stimulus evaluation process is largely preserved, whereas patients with demented Parkinsons disease have impairment of stimulus evaluation, go/no-go response selection, and execution.

Cerebral Blood Flow and Dementia in Parkinson's Disease

Regional cerebral blood flow (CBF) was examined in 27 patients with Parkinsons disease using single-photon emission computed tomography and N-isopropyl-p-[123I]iodoamphetamine as a tracer. Their CBF pattern was compared with that of seven patients with Alzheimers disease and nine age-matched neurologically normal controls. Tracer activity was determined in seven bilateral cerebellar, cortical, and subcortical regions and was expressed as the ratio of activity in each region to the mean tracer activity in the cerebellar region. Nineteen patients with nondemented Parkinsons disease showed significantly decreased tracer activity ratio in the frontal and temporal cortices, basal ganglia, and thalamus compared with that in controls. The eight demented Parkinsons disease patients showed significantly decreased tracer activity ratio in the temporal and parietal cortices compared with the patients without dementia, and demonstrated CBF pattern similar to that of patients with Alzheimers disease. These findings suggest that in patients with Parkinsons disease, the mechanism of CBF reduction of the frontal cortical region differs from that in the temporoparietal cortical region and support the concept that Parkinsons disease and Alzheimers disease may overlap in some patients. (J Geriatr Psychiatry Neurol 1991;4:194-203).

ORP150 ameliorates ischemia/reperfusion injury from middle cerebral artery occlusion in mouse brain

The 150-kDa oxygen-regulated protein (ORP150), a novel stress protein localized to the endoplasmic reticulum (ER), is induced by hypoxia/ischemia. To determine the role of ORP150 in cerebral infarction following ischemia/reperfusion, ORP150 transgenic (TG) and knockout (KO) mice were subjected to 1 or 3 h of middle cerebral artery (MCA) occlusion followed by reperfusion for 24 h. At 24 h after 1 h of occlusion, significantly less infarct volume was evident in cerebral cortex, but not in striatum, in ORP150TG than ORP150KO mice (P<0.001). Infarct volume did not differ significantly between these groups at 24 h after 3 h of occlusion. Immunohistochemical reactivity for microtubule-associated protein (MAP)2 in the MCA territory was lost in ORP150KO mice at 24 h after 1 h of occlusion. In contrast, MAP2 staining still was present in the affected cortex of ORP150TG mice, where markedly enhanced ORP150 immunoreactivity was demonstrated. MAP2 staining had disappeared from the affected area at 24 h after 3 h of occlusion in both groups, but astrocytic ORP150 reactivity was preserved in the ORP150TG group. At 6 h after 1-h occlusion, when MAP2 staining was evident in the affected cortex, some cortical neurons of the TG mice were reactive for Bcl-xS/L. Thus, ORP150 may be cytoprotective against ischemia/reperfusion injury via reduction of ER stress and probably also inhibition of apoptosis.