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.     

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.     

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.     

The brain diseases causing senile dementia

Summary Brains from 54 patients with organic dementia were examined systematically. As in previous investigations a predominance of Alzheimer type changes was observed. Seventeen patients showed Lewy bodies in the nucleus basalis, the substantia nigra and the locus coeruleus as well as other lesions of parkinsonian type. In 5 cases these changes were thought to be responsible for dementia. In 8 patients no convincing morphological substrate of dementia was found. These patients were older than average; therefore age per se might have been responsible for dementia. It is emphasized that subjective judgements are almost unavoidable in assessing the cause of organic dementia.     

Decreased densities of dopamine D1 receptors in the putamen and hippocampus in senile dementia of the Alzheimer type

The density and distribution of dopamine D1 receptors as labeled with [3H]SCH 23390 was analyzed in post-mortem brain tissue from patients with senile dementia of the Alzheimer type (SDAT) and in controls using quantitative autoradiography. In SDAT patients D1 receptor densities were markedly decreased in parts of the hippocampus, with reductions of up to 89% compared to the control values in the molecular layer of the dentate gyrus, 57% in the strata oriens and pyramidalis of the CA1 and 74% in the CA3 subfields. Significant decreases in D1 receptors were also observed in the putamen (23%) but not in the caudate and substantia nigra. A slight but not significant decrease of D1 binding was observed in most external layers of the temporal and occipital cortices.     

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.     

Comparison of DSIP- (delta sleep-inducing peptide) and P-DSIP-like (phosphorylated) immunoreactivity in cerebrospinal fluid of patients with senile dementia of Alzheimer type,multi-infarct syndrome,communicating hydrocephalus and Parkinson's disease

Summary The concentrations of delta sleep-inducing peptide (DSIP)-like (DSIP-LI) and P-DSIP-like (phosphorylated, Ser⁷) immunoreactivity (P-DSIP-LI) were measured by specific radioimmunoassay in the cerebrospinal fluid (CSF) of patients with senile dementia of the Alzheimer type [SDAT, subdivided into early (S1), middle (S2) and late dementia (S3)], multi-infarct dementia (MD), Parkinson's disease (PD), vascular disease (VD) and communicating hydrocephalus (H), as well as in control patients (C1, C2). Mean DSIP-LI and P-DSIP-LI concentrations were found to be significantly higher in the elderly control group (C1, mean age 83±5 years) than in the middle-aged control group (C2, mean age 40±16 years). DSIP-LI and P-DSIP-LI were positively correlated with age in both control groups. Significant decreases of DSIP-LI compared with age-matched controls (C1) were observed for S2, S3, MD, PD, VD and H. In contrast, no significant differences corresponding to pathology were found for P-DSIP-LI.     

Quantitative EEG in patients with presenile and senile dementia of the Alzheimer type

EEG data obtained from 27 patients with presenile Alzheimer's disease (AD) and 28 patients with senile dementia of the Alzheimer type (SDAT) were compared with data from 30 age- and sex-matched controls. Both patient groups exhibited more pronounced delta and theta activity and less prominent alpha and beta activity than the controls. AD, however, was accompanied by more severe slowing than SDAT. The slowing was distributed in the left temporal and frontal regions in AD, and bilaterally in the frontal regions in SDAT. As the severity of the dementia increased, delta activity alone increased in AD, whereas, there were significantly greater increases in both delta and theta activity and decreases in alpha and beta activity in SDAT. These EEG differences appear to be related to the degree of brain damage and the speed of progression of the disease process.     

Brain muscarinic receptors in senile dementia

Muscarinic receptors were analyzed in various post-mortem brain samples of 39 patients with different types of dementia and of 30 age-matched controls by the specific binding of [3H]QNB. The diagnoses were verified neuropathologically. The binding of [3H]QNB was significantly decreased in the hippocampus, amygdala and nucleus accumbens in patients with Alzheimer's disease (AD) and with combined type of dementia (CD), whereas in patients with multi-infarct dementia (MID) the binding was not significantly decreased in the limbic areas but only in the caudate nucleus. Of the clinical variables, orofacial dyskinesias in patients with AD but not with MID correlated with low brain weight and with the decreased [3H]QNB binding in the striatum and frontal cortex. The results reveal some differences between AD and MID. Changes in muscarinic receptor binding show that the cholinergic neurons in the limbic system are especially vulnerable in patients with AD and CD.     

Brain dopamine D-2 receptors in senile dementia

Summary Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of³H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of³H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between³H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia.     

The GBS scale in multi-infarct dementia and senile dementia of Alzheimer type

The GBS profile was assessed for 39 patients with multi-infarct dementia (MID) and 34 patients with senile dementia of Alzheimer type (SDAT). The MID patients fulfilled the DSM-III criteria for multi-infarct dementia and had a score of 7 points or more on the Hachinski Ischemic Scale (HIS) and a score of 4 points or less on the Gustafson/Nilsson Alzheimer Scale (GNAS). The SDAT patients fulfilled DSM-III criteria for primary degenerative dementia and had a score of 5 points or more on the GNAS and a score of 6 points or less on the HIS. The total GBS score, the GBS subscale and relative subscale scores for intellectual functioning were significantly higher in patients with SDAT as compared with patients with MID. However, these subscale scores were considerably dispersed and nearly totally overlapping between patients with MID and SDAT, which implicates that the discriminative value is minimal. The validity between the GBS versus HIS and between the GBS versus GNAS was divergent, suggesting that the GBS scale has its own unique validity. In conclusion, the study does not support the hypothesis that the GBS profile may be of diagnostic value in clinical differentiation between multi-infarct dementia (MID) and senile dementia of Alzheimer type (SDAT).     

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     

Autobiographical memory and executive function in early dementia of Alzheimer type

We studied executive function and autobiographical memory in a cohort of 33 DAT patients [divided into minimal (MMSE 24–30) and mild (MMSE 17–23) groups] and in 30 normal controls. Autobiographical memory, as assessed by autobiographical fluency and the Autobiographical Memory Interview (AMI), was impaired in DAT patients, even those with minimal disease. There was evidence of a gentle temporal gradient on the incident but not the personal semantic component of the AMI, suggesting that the two components are dissociable. Executive function was assessed by two separate dual performance tasks and letter fluency. Although there was a trend for minimal DAT patients to be impaired on executive tasks, this only reached significance for the mild group. Regression analysis suggested that the divided attention component of working memory was involved in the retrieval of personal semantic autobiographical memory, but verbal fluency was more important in the retrieval of autobiographical incidents. There was thus a dissociation in the type of executive function implicated in different subcomponents of autobiographical memory, arguing for subcomponents within executive function and autobiographical memory. The autobiographical memory deficit in DAT reflects, we argue, both impairment in retrieval processes, linked to executive function, and a loss of memory stores.     

Topography of the quantitative electroencephalogram in dementia of the Alzheimer type: Relation to severity of dementia

Conventional electroencephalographic (EEG) frequency bands and peak frequency were investigated in patients with probable dementia of the Alzheimer type (DAT). Measures of EEG topography and activity were also related to the severity of dementia, as assessed by neuropsychological tests. EEG activity measured in conventional frequency bands proved to be the most sensitive parameter for the quantitative differentiation of DAT, whereas the topography of peak frequency was the better qualitative discriminator between healthy subjects and DAT patients.     

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.     

Studies on neurotransmitter receptor systems in neocortex and hippocampus in senile dementia of the Alzheimer-type

Ligand binding to α₁-, α₂- and β-adrenergic, serotonin, benzodiazepine and GABA receptors was studied in neocortex and hippocampus of controls and patients with senile dementia of the Alzheimer-type. A selective loss of serotonergic binding sites characterised as a loss of both S1 and S2 sites was observed. The reduction in serotonin receptors did not correlate with a clinical assessment of the degree of dementia, or with the extent of Alzheimer-type neuropathological change.     

Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementia

Clinicopathological observations suggest there is considerable overlap between vascular dementia (VaD) and Alzheimer's disease (AD). We used immunochemical methods to compare quantities of amyloid-beta (Abeta) peptides in post mortem brain samples from VaD, AD subjects and nondemented ageing controls. Total Abeta peptides extracted from temporal and frontal cortices were quantified using a previously characterized sensitive homogenous time-resolved fluorescence (HTRF) assay. The HTRF assays and immunocapture mass spectrometric analyses revealed that the Abeta(42) species were by far the predominant form of extractable peptide compared with Abeta(40) peptide in VaD brains. The strong signal intensity for the peak representing Abeta(4-42) peptide confirmed that these N-terminally truncated species are relatively abundant. Absolute quantification by HTRF assay showed that the mean amount of total Abeta(42) recovered from VaD samples was approximately 50% of that in AD, and twice that in the age-matched controls. Linear correlation analysis further revealed an increased accumulation with age of both Abeta peptides in brains of VaD subjects and controls. Interestingly, VaD patients surviving beyond 80 years of age exhibited comparable Abeta(42) concentrations with those in AD in the temporal cortex. Our findings suggest that brain Abeta accumulates increasingly with age in VaD subjects more so than in elderly without cerebrovascular disease and support the notion that they acquire Alzheimer-like pathology in older age.     

Variability of senile dementia of Alzheimer type: A clinicopathological viewpoint

Senile dementia of Alzheimer type (SDAT) is a hetero-genous entity and can be grouped into different categories based on clinicopathological characteristics. Although the presence of senile plaques, neurofibrillary tangles and neuronal loss throughout the cerebral cortices plays an important role in the development of SDAT, the presence of these structures is not essential. Sociopsychological factors should also be considered as important factors in the development of SDAT in subjects over 80 years of age.     

87例老年期痴呆住院患者死亡分析

目的:探讨住院老年期痴呆的生存时间和死亡原因.方法:收集1994年4月～2002年4月间住院死亡的阿尔茨海默病(AD)和血管性痴呆(VD)病例共87例.了解其发病年龄,病程,住院天数和死亡原因.结果:AD组发病年龄和死亡年龄均显著高于VD组.两组生存时间差异无显著性.但AD组中男性生存时间显著短于女性.两组住院天数差异无显著性.两组死亡原因主要均为感染和全身衰竭.结论:我国住院的AD患者发病年龄和死亡年龄均晚于VD患者.女性AD患者生存时间长于男性患者.感染和全身衰竭是老年期痴呆的主要死亡原因.     

Orofacial dyskinesia and senile dementia of the Alzheimer type

Seventy-eight patients between the ages of 65 and 91 years with a diagnosis of semile dementia of the Alzheimer type were included in this study. They were assessed for the presence of abnormal movements using the Abnormal Involuntary Movement Scale and their cognitive functioning was assessed using the Mini Mental Test. Seventy-nine per cent of the patients had evidence of orofacial dyskinesia. Those patients with abnormal movements had greater degrees of cognitive impairment than those without. Orofacial movements were more common than similar movements of the extremities or trunk. Individuals with abnormal movements also tended to have higher levels of paranoid ideation.