Fifteen-year follow-up of 92 hospitalized adults with Down's syndrome: incidence of cognitive decline, its relationship to age and neuropathology

Background The clinical and neuropathological features associated with dementia in Down’s syndrome (DS) are not well established. Aims To examine clinico‐pathological correlations and the incidence of cognitive decline in a cohort of adults with DS. Method A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000. At outset, 87 participants were dementia‐free, with a median age of 38 years. Assessments included the Prudhoe Cognitive Function Test (PCFT) and the Adaptive Behavior Scale (ABS), to measure cognitive and behavioural deterioration. Dementia was diagnosed from case records and caregivers’ reports. Results Eighteen (21%) patients developed dementia during follow‐up, with a median age of onset 55.5 years (range 45–74). The PCFT demonstrated cognitive decline among those with a less severe intellectual disability (mild and moderate) but not among the profoundly disabled people (severe and profound). Clinical dementia was associated with neuropathological features of Alzheimer’s disease, and correlated with neocortical neurofibrillary tangle densities. At the age of 60 years and above, a little more than 50% of patients still alive had clinical evidence of dementia. Conclusions Clinical dementia associated with measurable cognitive and functional decline is frequent in people with DS after middle age, and can be readily diagnosed among less severely intellectually disabled persons using measures of cognitive function such as the PCFT and behavioural scales such as the ABS. In the more profoundly disabled people, the diagnosis of dementia is facilitated by the use of behavioural and neurological criteria. In this study, the largest prospective DS series including neuropathology on deceased patients, the density of neurofibrillary tangles related more closely to the dementia of DS than senile plaques. In people with DS surviving to middle and old age, the development of dementia of Alzheimer type is frequent but not inevitable, and some people with DS reach old age without clinical features of dementia.     

Brain tissue microarrays in dementia research: White matter microvascular pathology in Alzheimer's disease

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non‐neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well‐characterized materials (e.g. in quantitative mapping of white matter changes).     

The natural history of dementia in ageing people with intellectual disability

In a retrospective follow-up study over 11 years, the incidence and natural history of dementia was assessed in an institutionalized group of 144 people, aged 60 years and over, with mild to profound intellectual disability resulting from causes other than Down's syndrome. Age-related incidences, age at onset, duration and symptoms of dementia were comparable to those in the general population. The frequent and invalidating physical comorbidity (11 /11) hampered the diagnostic process in this group. The high prevalence of episodes of delirium (9/11) and depressive symptoms (8/11) as the first manifestations of dementia and/or during dementia might reflect increased vulnerability as compared to other ageing people.     

Going, going, gone . . . ? Implicit and explicit tests of conceptual knowledge in a longitudinal study of semantic dementia

Patients suffering from semantic dementia provide important constraints on theories of the structure and organisation of semantic memory. In this article we report one such patient, AM, whose progressive deterioration of semantics enables us to address the much-debated issue of whether conceptual structure is hierarchically organised. The hierarchical account predicts that brain damage should impair lower levels of the hierarchy (property information) before affecting higher level (category) information (Warrington and Shallice, Q. J. Exp. Psychol. 1975, 27, 635–657). We evaluate this prediction by repeated testing of AM in two studies—a semantic priming task and a verification task—over an 18 month period, contrasting the progressive deterioration of properties (functional and perceptual) and category relations (category co-ordinates and category labels). Properties were preserved longer than category information, arguing against a hierarchical account of semantic memory. In addition, functional properties were most robust to brain damage, supporting our claim that functional information plays a special role in semantic representations (Durrant-Peatfield et al., Proc. 19th Ann. Conf. of the Cognitive Science Society. Erlbaum, Mahwah, NJ, 1997, pp. 193–198. Tyler et al., Cognitive Neuropsychol. 1997, 14, 511–545).     

Aggressive behaviour in elderly psychiatric inpatients.

We describe the types of aggressive behaviour and determine their prevalence in a sample of hospitalized elderly psychiatric patients. Data were obtained by nurse ratings of aggressive behaviour using the recently developed Rating Scale for Aggressive Behaviour in the Elderly; 90 patients were rated over a 3-d period. Nearly half the sample were at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were high. In contrast, the frequency of injuries and the use of restraints and medication for aggressive behaviour were low. Some correlates of the aggressive behaviour were also analysed.     

Measurement of depression in dementia: Self vs clinician rating

The presence of depression was evaluated in a cross-section of 50 outpatients with dementia using the self-rated Geriatric Depression Scale and the clinician-rated Cornell Depression Scale. Impaired insight, as manifested by unawareness of dementia, correlated with dementia severity and discriminated a group of patients in whom the self-rated scale failed to show evidence of depression. Discrepancy between the two types of scales occurred among mildly as well as moderately demented patients when insight was impaired. Recognition of this discrepancy suggests that reliance on self-ratings may underestimate the presence and degree of depression among patients with dementia.     

Inappropriate social and sexual responses to a female student by male patients with dementia and organic brain disorder

Little attention has been directed toward inappropriate social and sexual approaches by patients with dementia diagnoses and organic disorders of the brain. A female student who approached patients who had dementia and organic brain disorders was frequently approached and touched in a sexual manner that was distressing to her and led her to believe that she was behaving in a manner that elicited these responses. It is recommended that students and volunteers be prepared for experience in settings with patients with these diagnoses through individual or group discussion, training and role playing as a way of enhancing their experiences and avoiding unnecessary feelings of guilt and embarrassment.     

太极通天液治疗血管性痴呆的疗效评价

目的：评价太极通天液治疗血管性痴呆的临床疗效。方法：随机将148例血管性痴呆分为太极通天液治疗组和丹参口服液对照组，另接应用韦氏成人智力量表评分，将血管性痴呆组分为3个亚组：即80－89分组，70－79分组和70分以下组，观察期为3个月。结果：太极通天液治疗前后WAIS－RC评分与对照组比较，80－89分组和70－79分组均有统计学差异（P＜0．05），而70分以下组无统计学差异（P＞0．05），结论：太极通天液对血管性痴呆有较好的治疗效果，且与痴呆病情程度有关。     

Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer''s disease: an autoradiographic study

We have used quantitative light microscopic autoradiographic techniques to analyze changes in muscarinic cholinergic receptors in the hippocampus in Alzheimer type dementia (ATD). The density and distribution of muscarinic cholinergic receptors has been correlated with the density of neurons, neuritic plaques and neurofibrillary tangles in the CA1 subfield of the hippocampus of control and ATD patients. The number of pyramidal cells per mm² in the CA1 sector was significantly decreased in ATD cases as compared to controls, although there were large variations among cases. The most marked reductions in cell counts were observed in patients with a history of profound dementia. The densities of muscarinic receptors, as well as the proportions of M₁ and M₂ subtypes, in the CA1 sector and dentate gyrus were not significantly different between ATD and old non-demented patients. Neuritic plaques, even in high numbers, did not affect the density of muscarinic receptors; moreover, the densities of receptors over the neuritic plaques did not differ from the surrounding neuropil. However, in some ATD cases there was a marked decrease in the concentration of these receptors in the CA1 sector and subiculum, with no change in the proportions of muscarinic receptor subtypes. These patients exhibited frequent extracellular remnants of neurofibrillary tangles (ghost tangles), but scarce neuritic plaques, and were those showing severe losses of pyramidal cells. There was a significant positive correlation between the total concentration of muscarinic receptors in the CA1 and the density of pyramidal cells, suggesting that decreases in receptor concentration result from a severe neuronal loss. We observed that the ratio of muscarinic receptors per pyramidal cell was significantly increased in ATD patients. This might indicate a possible upregulatory mechanism for muscarinic receptors in the population of remaining neurons in ATD. However, decreases of receptor numbers following severe neuronal fall out suggest that compensatory mechanisms are no longer possible in such cases. The question is raised whether these differences between cases reflect different diseases or different stages of the same disease.