Hiroto Shibayama

Electron microscopic structure of the alzheimer's neurofibrillary changes in case of atypical senile dementia

SummaryA man aged 70, showed early disorientation, memory defects, delusions and rages at 66, later mental deterioration with muteness and dysphagia. He died of cardiac failure. The postmortem examination revealed macroscopically and light microscopically the neuropathological findings of atypical senile dementia.Moreover, it is the interesting characteristic in the presented case that there are electron microscopically two types of filaments making the neurofibrillary tangles. One showed the so-called “paired helical filaments”, which were observed in the cerebral cortex. The other showed parallel “straight filaments”. These “straight filaments” were found in the bilateral hippocampi.

Granulovacuolar degeneration in the hippocampal cortex of aging and demented patients — a quantitative study

SummaryThe occurrence and topographic analysis of granulovacuolar degeneration (GVD) in the hippocampal cortex of mentally normal controls (75 cases) and patients with Alzheimers dementia (AD; 17 cases which included Alzheimers disease and senile dementia of Alzheimer type), multi-infarct dementia (MID; 16 cases), Picks disease (PD; 5 cases) and atypical dementia [5 cases; non-Alzheimer, non-Pick dementia with Fahrs syndrome (NANPDF)] were investigated. GVD was rarely found in control cases below the age of 60 years. In elderly normal brains, the statistically most representative ranking order of predilection for GVD (in decreasing severity) was: in the 60 s, CA1>prosubiculum >CA2 (no GVD was found in the CA3 and CA4); in the 70 s, CA1>prosubiculum >CA2 >CA3>CA4; in the 80 s, CA1>prosubiculum >CA2>CA3>CA4; in the 90s, CA1>prosubiculum >CA2>CA3>CA4. In the brains of demented patients, the rank order for GVD was: for AD, CA1 >CA2>CA3> prosubiculum >CA4; for MID, CA1 > prosubiculum >CA2>CA3>CA4; for PD, CA1 >CA2>CA3> prosubiculum >CA4; and for atypical dementia (NANPDF), CA1>CA2> prosubiculum >CA3>CA4. The similarity of the predilection to ranking order was noted both in normal aged subjects and in MID as well as both in AD and in PD. The qualitative investigation disclosed that the affected neurons with GVD in the cases of AD were found in all the examined areas outside the hippocampus (gyrus praecentralis, temporal and occipital cortex, globus pallidus, amygdaloid nuclei, mammillary bodies, medial thalamic nuclei, red nuclei, nuclei basalis of Meynert, dentate nuclei and inferior olivary nuclei) and, contrary to the results in AD, there were no affected neurons with GVD in the cases of MID. The occurrence and distribution of GVD in demented patients were different in these respective disorders.

Two distinct subgroups of senile dementia of Alzheimer type: Quantitative study of neurofibrillary tangles

The heterogeneity of senile dementia of Alzheimer type (SDAT) has been suggested by some authors clinically and neuropathologically. The heterogeneity of SDAT was investigated based on quantification of NFT combining Braak and Braaks neuropathological staging and the density of NFT in various areas of the cerebral cortex. Brain tissues were examined from 16 autopsy cases with clinically late onset dementia (>age 65) and neuropathologically diagnosed dementia of Alzheimer type (DAT). Gallyas–Braak staining was used for the quantification of NFT. The density of NFT was examined in the precentral gyrus, middle temporal gyrus (T2), parahippocampal gyrus and the amygdaloid nucleus. The 16 cases studied were divided into two groups depending on the number of NFT in the cortex (cut–off score: 5/mm2): the AD‐like group (NFT ≥ 5/mm2) and the common group (NFT < 5/mm2). The density of NFT in the precentral gyrus (t(3.225) = −9.007, P = 0.002) and T2 (t(3.365) = −3.774, P = 0.027) in the AD‐like group was significantly higher than those in the common group. However, no significant difference was observed in the parahippocampal gyrus between the two groups (t(14) = −0.318, NS). Moreover, there were no significant differences between the two groups as regards age at onset and the duration of the illness. The present study revealed the possible existence of two subgroups in SDAT having significantly different NFT densities in various areas of the cerebral cortex without any significant difference in their duration of illness. This classification has no relationship to Braak and Braaks staging, which depends only on the distribution of NFT, irrespective of their density. Arai et al. revealed that the NFT density in AD was significantly higher than in SDAT. We suggest that the neuropathological findings of the AD‐like group in SDAT resemble those of presenile AD.

An unusual case of Pick's disease

SummaryA man aged 64, with a history of chronic trichloroethylene intoxication, presented early headache, impairment of memory, and “stehende Redensarten”, later on mental deterioration with muteness and oral tendency. He died of bronchopneumonia.The brain was studied by light and electron microscopy. Numerous inflated cells, intraneuronal argentophil Pick bodies and central chromatolysis of neurons were found throughout the cerebral cortex. Widespread diffuse fibrillary gliosis was the finding bearing a striking resemblance to “progressive subcortical gliosis”. Severe loss of nerve cells was observed in the temporal lobe (except the posterior of T1) and moderate or mild loss in the gyrus rectus, insula, gyrus cinguli, and partial areas of the frontal, parietal, and occipital lobes. By electron microscopy, the argentophil Pick bodies consisted of a conglomeration of randomly arranged short 100–150Å filaments, ribosomes, vesicles mitochondria, and scanty paired helical filaments.The present case was considered to represent a rare case of Picks disease of the temporo-fronto-parieto-occipital type or panencephalic type.

Unusual cases of presenile dementia with Fahr's syndrome

Abstract: Three patients with an unusual type of presenile dementia were studied. Atypical clinical pictures emerged from an evaluation of these cases. Their symptoms and signs were thought to be neither those of Alzheimers disease nor those of Picks disease but a partial mixture of those of both diseases. The neuropathological changes were characteristic and the common findings were as as follows: 1) the absence of senile plaques, 2) the widespread presence of numerous neurofibrillary tangles, 3) a calcareous deposition of Fahrs type, 4) a circumscribed cerebral atrophy in the temporal or/and frontal lobes, 5) a moderate or severe demyelination and fibrous gliosis in the white matter of the atrophied areas, and 6) a slight or moderate neuronal loss in the nucleus basalis of Meynert. Similar cases reported previously were reviewed.

Clinicopathological study of diffuse neurofibrillary tangles with calcification: With special reference to TDP-43 proteinopathy and alpha-synucleinopathy

Diffuse neurofibrillary tangles with calcification (DNTC) is a relatively rare presenile dementia that clinically shows overlapping symptoms of Alzheimers disease and frontotemporal lobar degeneration (FTLD). DNTC is pathologically characterized by localized temporal or frontotemporal atrophy with massive neurofibrillary tangles, neuropil threads and Fahrs-type calcification without senile plaques. We tried to clarify the molecular basis of DNTC by immunohistochemically examining the appearance and distribution of accumulated alpha-synuclein (aSyn) and TAR DNA-binding protein of 43kDa (TDP-43) in the brains of 10 Japanese autopsy cases. We also investigated the clinically characteristic symptoms from the clinical charts and previous reports, and the correlations with neuropathological findings. The characteristic symptoms were evaluated using the Neuropsychiatric Inventory Questionnaire (NPI-Q). As a result, we confirmed the high frequency of neuronal cytoplasmic accumulation of aSyn (80%) and phosphorylated TDP-43 (90%) in DNTC cases. There was a significant correlation between some selected items of NPI-Q scores and the severity of the limbic TDP-43 pathology. The pathology of DNTC included TDP-43 and aSyn pathology with high frequency. These abnormal accumulations of TDP-43 might be involved in the pathological process of DNTC, having a close relationship to the FTLD-like psychiatric symptoms during the clinical course.

Activation mechanism of brain microglia in patients with diffuse neurofibrillary tangles with calcification: a comparison with Alzheimer disease.

Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia and is characterized pathologically by diffuse neurofibrillary tangles (NFTs) without senile plaques (SPs). In this study, we investigated the distribution of human leukocyte antigen (HLA)-DR–positive activated microglia in postmortem brain tissue of six patients with DNTC and six patients with Alzheimer disease (AD). HLA-DR–positive activated microglia were observed to associate with SPs in AD. In the DNTC brain, which lacks SPs, HLA-DR–positive microglia were mainly accumulated around weakly tau-positive NFTs, which were also positive for anti–amyloid-P and anti-C3d antibodies. The results of this study suggest that the complement pathway is also activated in the DNTC brain and that immune and inflammatory responses, including microglia activation, may occur around extracellular NFTs in DNTC patients.

Sleep problems in the aged in relation to senility

Abstract As a part of an epidemiologic survey of dementia in a community of aged persons, correlation between sleep complaints and physical illness and senility were studied. A total of 3302 randomly sampled aged individuals (aged 65 yean) were studied using a questionnaire. In this sample the prevalence of poor sleep and habitual snoring did not increase with age. The prevalence of excessive daytime sleepiness showed an increase with age. Male predominance of habitual snoring and female predominance of poor sleep were observed. Female predominance of excessive daytime sleepiness was noted among the aged 70 and over. Age‐related excessive daytime sleepiness was significantly correlated with senility.

A case of dementia with Lewy bodies that temporarily showed symptoms similar to Creutzfeldt–Jakob disease

We discuss a case of a 67‐year‐old male with dementia with Lewy bodies (DLB) that was initially suspected as Creutzfeldt–Jakob disease (CJD) or another type of encephalopathy, because he showed rapidly progressive deterioration, myoclonus, gait disturbance and a decline in activities of daily living. The present study describes a clinically atypical case with probable DLB and reviews similar cases in the literature, and we propose a rapidly progressive clinical subtype of DLB.

Assessment of Competency to Contract for Care Insurance in Aichi Prefecture

Background: A nursing care insurance system went into effect in April 2000 in Japan. Under the new system, the user (person requiring care) enters a contract directly with the service provider. Hence a pertinent issue is whether or not the user has the decision‐making capacity to enter a contract (competency to contract) and the degree of that capacity. The aim of the present study was to gain an understanding of the competency to contract under the new system.