混合型痴呆的临床特征及追踪研究

追踪调查了２６例混合型痴呆（ＭＩＸ）患者的临床特征，与多发梗塞性痴呆（ＭＩＤ）及Ａｌｚｈｅｉｍｅｒ病（ＡＤ）患者进行对照研究，发现其临床特点倾向于ＭＩＤ，神经体征的出现比ＡＤ更能提示有脑损害，近期疗效明显优于ＡＤ组。门诊随访８个月，病情波动者明显多于ＡＤ组，病程中恶化者明显少于ＡＤ组。二次ＣＴ对照表明，３３．３％的ＭＩＤ和７５．０％的ＡＤ发展成脑萎缩和梗塞并存的混合性脑损害，提示一部分ＭＩＸ者由ＭＩＤ发展而来，并非完全是老年性痴呆的一个亚型。其疾病本质有待进一步研究。     

Recent advances in dementia research in Japan: Alzheimer-type dementia

In a previous article, recent reports by Japanese researchers on non-Alzheimer-type degenerative dementias were reviewed. In the present article, recent Japanese reports on Alzheimer-type dementia (ATD) are reviewed. Alzheimer-type dementia has received great attention and has been studied from various viewpoints in Japan as well as in Europe and the Americas. In Japan, although it was believed that vascular dementia was the most frequent dementia in the elderly, ATD has recently been shown to be the most predominant type of dementia. Such a great number of papers on ATD have been reported in Japan that mainly the clinical, neuropathological, biochemical and molecular biological research papers alone are reviewed here.     

住院老年痴呆患者的病情严重程度及其有关因素分析

目的了解住院老年痴呆患者的病情严重程度及其影响因素.方法76例住院痴呆患者,其中AD42例,MID34例,平均年龄(75.89±8.04)岁,平均病程(4.94±3.15)年,平均住院时间(2.27±2.06)年,评定工具为MMSE、ADL、ADSS、SBS和PANSS.结果不同性别和文化程度的中晚期痴呆患者的认知功能,日常生活能力无显著差异,AD和MID之间各量表分也元差异(P＞0.05),痴呆程度较重的患者异常行为和锥体外系征发生率及程度均较高(P＞0.05).结论AD和MID至后期痴呆时已无临床差异,不同性别、不同文化程度对中晚期痴呆严重程度的影响不大.但男性、文化程度低、PANSS、RSESE分高的患者痴呆发展速度较快.     

Defining dementia: clinical criteria for the diagnosis of vascular dementia

The recognition of cerebrovascular disease (CVD) as a contributing factor and a cause of dementia has led to the development of clinical criteria for vascular dementia (VaD). Due to high specificity, the consensus criteria developed by the National Institute for Neurological and Communicative Disorders and Stroke (NINDS)–Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) have been used in controlled clinical trials to select patients with pure VaD. VaD is predominantly a subcortical frontal form of dementia with prominent executive dysfunction. In contrast, the criteria of the NINCDS–Alzheimer's Disease and Related Disorders Association (ADRDA) emphasize memory loss as the main feature to distinguish Alzheimer's disease (AD) from VaD and from other forms of dementia. Moreover, CVD may precipitate the clinical expression of AD. Although no criteria have been created specifically for patients having AD with CVD, the ischemic score, the Informant Questionnaire on Cognitive Decline in the Elderly and a history of prestroke mild cognitive impairment (MCI) may be useful for identifying patients with this mixed form of dementia.     

Establishment of a monoclonal antibody against senile plaques and its application for immunohistological and immunoelectron microscopical studies in the brain of the elderly

Summary A monoclonal antibody (Am-3) was produced against senile plaques in the brain of a patient with Alzheimer's disease. Am-3 was reactive with senile plaques of typical, primitive and diffuse type not only in the brain used as immunogen, but also those in the brain of 15 out of 25 autopsy cases of the aged people. Moreover, Am-3 was also reactive with granular materials of various sizes scattered in the 1st, 3rd and 4th layers of the cerebral cortices of the cases with severe dementia. Am-3 was also reactive with vessel wall of the congophilic angiopathy. By immunoelectron microscopic examination, Am-3 was positive with amyloid fibril in the core and crown of senile plaques, and in the congophilic angiopathy.     

Senile dementia of Alzheimer type characterized by laminar neuronal loss exclusively in the hippocampus,parahippocampus and medial occipitotemporal cortex

Summary Seven cases of senile dementia of Alzheimer type (SDAT) with unusual clinico-pathological findings are reported. The patients showed neuronal loss in laminar pattern, with gliosis exclusively confined to the CA1 of the hippocampus, the area of the hippocampal gyrus (entorhinal cortex) and medial occipitotemporal cortex. This change was more pronounced in the oral region. The subcortical white matter showed more pronounced fibrillary gliosis than loss of myelin. Both Alzheimer's neurofibrillary tangles and senile plaques were less marked than those usually seen in SDAT. The mental disturbance started after the age of 65 in all patients. The main clinical feature was marked character change in addition to disturbance of cognitive function. Cranial computed tomography showed marked dilatation of the oral portion of the inferior horn of the lateral ventricle in the early stage. It was apparent that although the cases in this group could be incorporated within in the spectrum of SDAT, they could also be considered to represent a variant of SDAT. This group could contribute to an understanding of the clinico-pathological spectrum of SDAT as well as indicating ways of managing such patients.     

Laminar distribution of neocortical senile plaques in senile dementia of the alzheimer type

Summary A prospective longitudinal study was undertaken in a geriatric hospital on women over 75 years of age, clinically diagnosed as either intellectually normal or having senile dementia of the Alzheimer type (SDAT) of varying degrees of severity. Mental impairment was assessed prospectively. Fifteen brains from this population were studied to evaluate quantitatively the distribution of senile plaques (SP) in relation to cortical lamination. SP density in four neocortical areas (first temporal gyrus; supramarginal gyrus calcarine area; precentral gyrus) was significantly correlated with the degree of mental impairment. SP distribution in the cortical layers was evaluated by an indirect method and appeared to be fairly constant from one case to another. Significantly higher SP densities were observed in layers II and III of the temporal and occipital samples, while minimal values were noted in layer I. Lower densities of SP were found in layers V and IV of the occipital and temporal lobes. These data suggest a selective vulnerability of some areas of cortical projections in SDAT.This work was presented at the meeting of the Société Française de Neurologie (Paris; 7, March 1985) and at the meeting of the club Français de Neuropathologie (Marseilles, 28, June 1985)Partly supported by INSERM (PRC Santé Mentale et Cerveau no. 133015) and FRMF     

Alzheimer dementia and Pick's disease: neurofibrillary tangles and Pick bodies are associated with identical phosphorylated neurofilament epitopes

Summary Section of formaldehyde-fixed paraffinembedded cortical and hippocampal brain tissue from five cases with senile dementia of Alzheimer type (SDAT) and five cases with Pick's disease (PD) were immunostained with the monoclonal antibodies (mabs) 147, RT 97, BF 10 and 8D8 with and without pretreatment with alkaline phosphatase (AP) or trypsin (Tr). The mabs 147, RT 97 and BF 10 had previously been demonstrated to bind exclusively to phosphorylated epitopes of neurofilament proteins, while mab 8D8 is shown in this report to bind mainly, but not exclusively, to phosphorylated neurofilament epitopes. The mabs RT 97, BF 10 and 8D8, but not 147 stain most, if not all, Pick bodies (PB) and Alzheimer neurofibrillary tangles (NFT). When sections are pretreated with AP or Tr the immunostaining with mab BF 10 is very resistent in both PB and NFT. This resistance of PB and NFT is in contrast to the reduced staining of axons and of swollen cells in PD by the same enzymatic pretreatment. Immunostaining with mab RT 97 of PB and NFT is reduced moderately by AP and considerably by Tr. Only when stained with mab 8D8 is there a discrepancy between PB and NFT in their reaction to the pretreatment with AP: NFT staining with mab 8D8 is not affected, while that of PB is abolished. Thus, in spite of their different ultrastructure, PB and NFT are very similar immunocytochemically and in the accessibility of their phosphorylated epitopes to enzymatic treatment.Supported partially by the Medical Research Council of Great Britain, The Welcome Trust, London, UK, and Sandoz LTD, Basel, Switzerland     

Alzheimer''s disease and senile dementia of Alzheimer type

Clinical and neuropsychological findings, EEG, and several blood and CSF parameters were investigated in 36 patients with Alzheimer's disease (AD) and 35 patients with senile dementia of Alzheimer type (SDAT). There were more women among senile patients and more familial cases among presenile patients. The average duration of the symptoms was longer in presenile patients (6.1 years) than in senile patients (3.9 years). This could be due to the lower resistance to the disease process in the senile group.
Extrapyramidal signs, especially rigidity, were found in over 60 % of all patients and in practically all patients with advanced dementia. Tremor was found in three patients only. Four presenile (11 %) and two senile (6 %) patients had epileptic seizures. All patients had abnormal EEG recordings, mainly in form of diffuse slowing. A positive correlation was found between the EEG abnormality and the severity of dementia in AD but not in SDAT. However, the difference between the correlation coefficients in AD and SDAT was insignificant. Between EEG and the duration of the disease there was no correlation. EEG was not more abnormal in very severe dementia than in severe dementia. Other findings were similar in AD and SDAT.
It is concluded that it is artificial to separate AD and SDAT at the age of 65 and that they clinically compose a single entity. This entity could well be called Alzheimer's disease.     

Activation of vasopressin neurons in the human supraoptic and paraventricular nucleus in senescence and senile dementia

A recent study has shown that vasopressin (AVP) cells in the human supraoptic (SON) and paraventricular (PVN) nuclei increase in size after 60 years of age, suggesting that AVP production is increased in senescence. In the present study, the same brain material was used for the determination of nucleolar size in immunocytochemically identified AVP and oxytocin (OXT) neurons as an additional parameter for peptide production.A strong correlation was found between nucleolar size and cell size, both in AVP and OXT neurons. Nucleolar size of AVP but not of OXT neurons increased significantly in senescence. Observations in brains from patients with senile dementia of the Alzheimer type (SDAT) were commensurate with their ages. These results strongly support the hypothesis that AVP neurons in the SON and PVN are activated in old age.     

Increased chemiluminescence response of neutrophils from the peripheral blood of patients with senile dementia of the Alzheimer's type

The metabolic activity of circulating neutrophils from patients with senile dementia of the Alzheimer's type (SDAT) was investigated by a chemiluminescence assay and compared with that of old and young healthy controls. Neutrophils from demented patients showed a higher and faster chemiluminescence emission than those of controls when activated in vitro by autologous or heterologous sera. Granulocytes from patients with Parkinson's disease did not show an increased chemiluminescence activity. Moreover, serum from patients with SDAT depressed the chemiluminescence emission of granulocytes from young donors. Serum levels of α₁-antichymotrypsin (α₁-ACT) were also determined and were found to be higher in demented subjects than in old and young controls. These data suggest that peripheral and systemic indexes of inflammation are present in the disease and might be associated with mental deterioration.     

Cognitive deficits of mild dementia:A comparison between dementia of the Alzheimer's type and vascular dementia

Abstract This study was designed to examine the profiles of cognitive deficits in 11 mildly demented patients with dementia of Alzheimer's type (DAT), five with vascular dementia with multiple subcortical lacunar infarcts (VDS), and seven with vascular dementia with extensive white matter lesions (VDW) in comparison with 23 aged individuals without dementia. Memory, attention, abstract thinking, and visuospatial function were assessed using the Japanese translation of the Wechsler Memory Scale-Revised (WMS-R) and the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Compared with normal aged individuals, three dementia groups were significantly impaired in the memory and abstract thinking. However, the performances on several tests on attention (i.e. Mental Control and Visual Memory Span Backward from WMS-R) and visuospatial function (i.e. Object Assembly from WAIS-R) differed significantly between the DAT and VDS groups, with VDS being the worst in terms of performance than was DAT. This study suggests that, in the mildly demented stage, the patients with DAT have few problems in the attention and visuospatial function, but those with VDS have impairments in these cognitive abilities.     

Olfactory dysfunction in dementia of Alzheimer's type and vascular dementia

Background: Olfactory function in vascular dementia has not been extensively investigated to date. We studied olfactory function in vascular dementia (VD) and dementia of Alzheimer's type (DAT). Methods: We studied olfactory functioning in 12 patients suffering from dementia of Alzheimer's type, 11 patients with vascular dementia and 30 normal subjects. For these subjects we examined a 12‐item version of the Pennsylvania smell identification test and mini‐mental state examinations. These three groups were matched for age, sex and educational level. Results: Although the dementia scores were comparable in the DAT and VD groups, the smell identifications were low in DAT patients compared with VD patients and normal control subjects. Conclusions: These results suggest that the smell identification test may be useful in differential diagnosis between DAT and VD patients     

Senile dementia of Alzheimer type: Astroglial reaction to extracellular neurofibrillary tangles in the hippocampus

Summary Two types of Alzheimer neurofibrillary tangles may be found in the hippocampus in senile dementia of the Alzheimer type. Besides classical flameshaped intraneuronal tangles, there are less compact tangles representing extracellular remnants of destroyed neurons with neurofibrillary change. Strong immunoreactivity for glial fibrillary acidic protein (GFA) was found in the second type of tangles, which was due to penetration of fine processes of fibrous astrocytes into bundles of paired helical filaments (PHF). PHF appear to be a strong stimulus for astrocytic reaction when they are not segregated from the neuropil by the neuronal cell membrane.     

Senile dementia of the neurofibrillary tangle type (tangle‐only dementia): Neuropathological criteria and clinical guidelines for diagnosis*

Senile dementia of the NFT type (SD‐NFT) is a subset of dementia in the elderly, characterized by numerous NFT in the hippocampal region and absence or scarcity of senile plaques throughout the brain. Senile dementia‐NFT has also been referred to as tangle‐only dementia, NFT‐predominant form of SD, SD with tangles, or limbic NFT dementia. Herein are proposed the criteria for neuropathological diagnosis of SD‐NFT: (i) late‐onset dementia with abundant NFT in the hippocampal region and absence or scarcity of senile plaques (amyloid β protein deposits) throughout the brain; and (ii) exclusion of other dementias with NFT. Some elderly individuals suffering from memory disorder without obvious dementia have neuropathological findings similar to SD‐NFT, and they would represent a condition in the process of formation of the SD‐NFT pathology. Guidelines for the clinical diagnosis of SD‐NFT are also proposed; development of reliable diagnostic tests is necessary to differentiate AD and other neurodegenerative dementias from SD‐NFT.     

Clinical and biochemical responses to therapy in Alzheimer's disease and multi-infarct dementia

Summary Memory performance, central monoaminergic function and sympathetic nerve activity were studied in patients with dementia of the Alzheimer type (DAT) or with multi-infarct dementia before and after 4 weeks with single or combined drug therapy (choline-piracetam). Analysis of the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxy-4-hydroxyphenylacetic acid (HVA) and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) and also in urine (plus 3-methoxy-4-hydroxy mandelic acid) showed that the basal values of HVA in the CSF and urine were lower in the more severely demented compared with the mildly demented subjects in both groups. The combined drug treatment resulted in a statistically significant increase in the MHPG level in the CSF of mildly demented subjects of the DAT group, while it seemed not to influence the other monoamine metabolites. The sympathetic nerve activity was similar in both patient groups and was unchanged after therapy. These findings suggest a dopaminergic deficit in advanced stages of the disease and a possible enhancement of the central noradrenergic output with therapy. No effects of therapy on memory performance or correlations between monoamine levels and memory test scores were noted.     

Tau,paired helical filaments and amyloid in the neocortex: a morphometric study of 15 cases with graded intellectual status in aging and senile dementia of Alzheimer type

Summary Tau immunoreactivity was studied in temporal neocortex, area 22, in 15 cases with graded intellectual status and compared with the immunoreactivity observed with an antiserum against paired helical filaments (PHF) and with the density of amyloid revealed by thioflavin S. Samples came from women over 75 years either intellectually normal or affected by senile dementia of the alzheimer type at various degrees of severity. Mental status had been prospectively assessed by the Blessed's test score. Antitau labelled a neuropil meshwork, the density of which increased with the severity of the disease. This meshwork was denser in layers II, III and V in the most affected cases. The number and the size of the taupositive fibers within the senile plaques increased with the intellectual deficit. Senile plaques were more numerous in layers II and III and neurofibrillary tangles in layers III and V whatever the staining technique: tau or PHF immunocytochemistry, and thioflavin S. The densities of senile plaques and of neurofibrillary tangles (NFT) were correlated with the severity of the disease whatever the staining method. The three methods revealed a systematically different number of changes. This systematic difference could greatly influence the neuropathological diagnosis. It could be the consequence of various factors: different sensitivities of the staining methods or changes in the antigenic and amyloid composition of the lesion according to the stage of the disease. In line with the last hypothesis, a higher proportion of amyloid-rich plaques was noted in the less affected cases, suggesting that tau and PHF epitopes appeared secondarily. Tau epitopes seemed to be present at least as early as PHF epitopes in the NFT. The pathological changes best linked to dementia were NFT revealed by tau antiserum.Supported by a fellowship from the European Community Commission (PD)     

The Comprehensive Psychopathological Rating Scale in patients with dementia of Alzheimer type and multiinfarct dementia

ABSTRACT– Eighteen patients with the clinical diagnosis dementia of Alzheimer type (AD/SDAT) and 20 patients with the clinical diagnosis multiinfarct dementia (MID) were interviewed using a subscale to the Comprehensive Psychopathological Rating Scale (CPRS), consisting of items measuring psychopathological symptoms and signs commonly seen in patients with dementia. The aim of the investigation was to evaluate whether a difference in psychopathology between AD/SDAT and MID could be observed during a semistructured psychiatric interview using the CPRS. In both groups the duration of illness was similar and the dementia mild to moderate. All patients were subjected to somatic, psychiatric, laboratory, neurophysiologic and neuroradiologic examinations in order to obtain the correct clinical diagnoses. The results show that patients with AD/SDAT have a more variable psychopathology than patients with MID. Patients with MID were rated lower on all items used, especially those concerning verbal and personal contact. This might explain the generally accepted opinion that patients with MID have better contact with their surroundings and better preservation of their personality, even though they have the same degree of dementia as patients with AD/SDAT.     

CT study in senile dementia of Alzheimer type

We evaluated 14 patients with senile dementia of Alzheimer type (SDAT) and 15 age-matched normal elderly controls using psychological test and computed tomography scans. The low-density rate (LDR) was used as an index of brain atrophy. SDAT patients had significantly higher scores on the Hasegawa Dementia Scale (p< 0.01) and significantly lower scores on the Bender Gestalt Test (p<0.01) than control subjects. The LDRs of the left and right hemispheres were significantly higher in the SDAT group than in the control group in all three slices investigated (p<0.05/6 = 0.0083). In SDAT patients, significant diagnosis by hemisphere interaction was observed in one slice (p<0.05), with higher LDR on the left than on the right (p<0.05/6 = 0.0083). Our findings suggest that cortical atrophy is predominant on the left side in patients with SDAT.