Yuta Manabe

Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan, a traditional Japanese medicine.

Background:  This multicentre open‐label trial examined the efficacy and safety of the traditional Japanese medicine, or Kampo medicine, yokukansan (YKS), for behavioural and psychological symptoms of dementia (BPSD) in patients with dementia with Lewy bodies.

Evaluation of Probable or Possible Dementia with Lewy Bodies Using 123I-IMP Brain Perfusion SPECT, 123I-MIBG, and 99mTc-MIBI Myocardial SPECT

We evaluated the diagnostic usefulness of combination studies with a statistical mapping method in N-isopropyl-p-123I-iodoamphetamine (123I-IMP) brain perfusion SPECT, cardiac sympathetic nerve function by 123I-metaiodobenzylguanidine (123I-MIBG), and myocardial function by electrocardiographically gated 99mTc-sestamibi (99mTc-MIBI) SPECT for patients with probable or possible dementia with Lewy bodies (DLB). Methods: Twelve patients with probable DLB (7 male, 5 female; mean age ± SD, 72.3 ± 5.63 y; range, 65–82 y) and 9 patients with possible DLB (3 male, 6 female; mean age ± SD, 73.1 ± 9.23 y; range, 59–88 y) were enrolled in this study. 123I-IMP SPECT images were analyzed with 3-dimensional stereotactic surface projections (3D-SSP) and the severity of ischemia was classified objectively using quantitatively analytic and display software; stereotactic extraction estimation (SEE) methods were compared with a normal database. In addition, we evaluated 123I-MIBG heart-to-mediastinum (H/M) uptake ratios. Moreover, we performed 99mTc-MIBI SPECT to evaluate myocardial perfusion and the left ventricular ejection fraction (LVEF) compared with a normal database. Results: 3D-SSP images of group comparison with healthy control subjects showed significantly decreased perfusion in the parietotemporal, occipital cortex, posterior cingulated, and precuneus regions in the probable DLB group but no significant reduction in the possible DLB group. Mean H/M ratios in the probable DLB group were significantly lower than those of the possible DLB group and the control group, respectively. Ten of 12 patients (83.3%) with probable DLB and 1 of 9 patients (11.1%) with possible DLB showed severe reduction in the bilateral occipital lobe and also a low 123I-MIBG uptake. One patient (8.3%) with probable DLB and 2 patients (22.2%) with possible DLB showed no bilateral occipital hypoperfusion but showed low 123I-MIBG uptake. One patient (8.3%) with probable DLB and 6 patients (66.7%) with possible DLB showed no occipital hypoperfusion and normal 123I-MIBG uptake. 99mTc-MIBI gated SPECT did not indicate any wall motion abnormality in any subjects. Conclusion: These results suggest that combined examination of cerebral blood flow with 3D-SSP and SEE analysis, and cardiac sympathetic nerve function with 123I-MIBG, would be a useful supporting diagnostic method in patients with DLB—particularly, in possible DLB and when cerebral blood flow does not indicate occipital hypoperfusion.

OPEN LABEL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF YOKUKANSAN, A TRADITIONAL ASIAN MEDICINE, IN DEMENTIA WITH LEWY BODIES

cian’s choice to recommend surgery, taking into consideration the likelihood of perioperative mortality and postoperative complications, but advanced patient age alone should not prevent the surgeon from proceeding to surgery if clinically indicated. In particular, available data support pursuit of elective surgical procedures in nonagenarians and suggest that such procedures in this age group have an acceptable risk of morbidity and mortality. Laparoscopic approaches in nonemergent settings, in carefully selected nonagenarians, may reduce overall morbidity and shorten the recovery period.

Neuropsychological Detection of the Early Stage of Amnestic Mild Cognitive Impairment without Objective Memory Impairment

Aim: We investigate the assessment method to detect the early stage of amnestic mild cognitive impairment (aMCI) using Wechsler Memory Scale – Revised (WMS-R) and Wechsler Adult Intelligence Scale – Third Edition (WAIS-III). Methods: Three groups (normal group, aMCI group, and early aMCI group), controlled for age and years of education, underwent brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), WAIS-III, WMS-R, and other tests. The early aMCI group does not fulfill the clinical diagnostic criteria of aMCI because patients do not have objective memory impairment, but their clinical symptoms and results of 18F-FDG PET indicate that they should be included in the category of aMCI. Results: The discrepancy of scores between Verbal IQ and General Memory had the highest accuracy in discriminating between normal and early aMCI groups. Conclusion: The cutoff point determined in this study is useful to detect an early stage of aMCI, which may be distinguished from aMCI using the current criteria.

123I-metaiodobenzylguanidine myocardial scintigraphy with early images alone is useful for the differential diagnosis of dementia with Lewy bodies

123I-metaiodobenzylguanidine cardiac scintigraphy (MIBG) is a useful imaging technique for the diagnosis of dementia with Lewy bodies (DLB). However, MIBG has a serious disadvantage in that it demands a long examination time. The objective of this study was to evaluate statistically the usefulness of the heart/mediastinum ratio (H/M) from the early phase of MIBG for the differential diagnosis of DLB. In total, 113 patients were examined, including 32 non-DLB (19 with Alzheimers dementia) and 79 DLB patients. The mean early-H/M ratio was 2.83 in the non-DLB group and 1.95 in the DLB group. The mean delayed-H/M ratio was 3.0 in the non-DLB group and 1.76 in the DLB group. With a cutoff point of 2.27 on early images, the sensitivity, specificity, and diagnostic accuracy were 65%, 94%, and 73%, respectively, and the area under the curve was 0.82, indicating moderate accuracy. This analysis indicates that images from the early phase of MIBG alone are sufficient for the differential diagnosis of Alzheimers disease and DLB.

Three presenile patients in which neuropsychological and neuroimaging examinations suggest possible progression to dementia with Lewy bodies.

We report three presenile patients who were initially suspected of having Alzheimers disease (AD) or being in the prodromal stage of AD, regardless of visuoperceptual dysfunctions in daily living, because they lacked the core features and prodromal non‐motor symptoms of dementia with Lewy bodies. Subsequently, progression to dementia with Lewy bodies was suspected based on neuropsychological and neuroimaging findings; additionally, one of the three patients suffered from visual hallucinations. Neuropsychological examinations such as subjective contours, cube copying and block design in the Wechsler Adult Intelligence Scale‐III revealed visuoperceptual dysfunction in all three patients even when other cognitive functions were rather preserved. Brain magnetic resonance imaging revealed no significant brain atrophy, including in the parieto‐occipital area and the hippocampus, while brain 18F‐fluorodeoxyglucose positron emission tomography demonstrated right dominant metabolic reductions in the occipital lobe, including the primary visual cortex, in all three patients. We suggest the possibility of progression to dementia with Lewy bodies, but not AD or posterior cortical atrophy. Regardless of the presence of core features and prodromal non‐motor symptoms, this progression is suggested when there are difficulties only in higher‐level visual processing such as subjective contours and block design in the Wechsler Adult Intelligence Scale‐III, no significant atrophy of the parieto‐occipital area and hippocampus on brain magnetic resonance imaging, and hypometabolism in the occipital lobe including the primary visual cortex on brain 18F‐fluorodeoxyglucose positron emission tomography.

The first autopsied case of diffuse Lewy body disease (DLBD): re-examination by recent immunostaining methods: The 50th Anniversary of Japanese Society of Neuropathology.

Materials from our first autopsied case of diffuse Lewy body disease (DLBD), that was originally reported in 1976, were re‐examined using recent immunohistochemical methods. Lewy pathology consisting of Lewy bodies and Lewy neurites appeared much more marked with alpha‐synuclein immunostaining than had been detected with classical stainings. This case and our other similar cases prompted us to propose the terms “Lewy body disease” in 1980 and “diffuse Lewy body disease” in 1984. We also reported in 1990 that DLBD was classified into two forms: a pure form and a common form. Based on these studies the term “dementia with Lewy bodies (DLB)” was proposed in 1996. Since 1980, we have insisted that DLB, Parkinson disease (PD), and PD with dementia (PDD) should be understood within the spectrum of Lewy body disease. This insistence has been recently accepted by the International Workshop and the International Working Group on DLB and PDD in 2005 and in 2006, respectively.

Increased dosage of donepezil for the management of behavioural and psychological symptoms of dementia in dementia with Lewy bodies.

As with other types of dementia, the behavioral and psychological symptoms of dementia (BPSD) can make caregiving difficult for patients with dementia with Lewy bodies (DLB). We hypothesized that administration of donepezil at an increased dose of 10 mg/day might dose‐dependently improve BPSD in DLB patients with relapse, after their symptoms had been controlled initially by donepezil therapy at the standard dose.

Behavioral and Psychological Symptoms of Dementia

Behavioral and psychological symptoms of dementia (BPSD) are observed in all forms of dementia. We discuss representative forms of BPSD such as hallucination and delusion, depression, and rapid eye movement (REM) sleep behavior disorder (RBD) observed in patients with dementia with Lewy bodies (DLB). The most representative BPSD for DLB is visual hallucination. McKeith et al. reported that 80 % of DLB cases involved visual hallucination. Delusions occur more frequently in DLB, compared with Alzheimer’s disease (AD). These in the patients with DLB are characterized by delusional misidentification either as a continuation of visual hallucinations or related to delusions resulting from visual misidentification of places, people, or surroundings. Depression is one of the first symptoms of DLB and is listed in the CDLB guidelines as one of the supportive features. One suggestive sign of DLB is rapid eye movement (REM) sleep behavior disorder (RBD), which is significantly more common in the patients with DLB than other forms of neurodegenerative dementia. RBD also occurs earlier than cognitive dysfunction and primary core symptoms such as parkinsonism and visual hallucination.