Cause-specific mortality of people with intellectual disability in a population-based, 35-year follow-up study.

The aim of the present study was to investigate cause-specific mortality in people with intellectual disability (ID). It was based on a 35-year follow-up study of a nation-wide population of 2369 subjects aged between 2 and 97 years. The 1095 deceased people had accumulated 64 539 person-years. The research took the form of a prospective cohort study with mortality follow-up. Observed and expected deaths were calculated as standardized mortality ratios using the Finnish general population as the reference. Cause-specific mortality ratios were calculated by the level of ID, sex and age. The three most common causes of death were cardiovascular diseases, respiratory diseases and neoplasms. Disease mortality was high up to 40 years of age, but did not increase thereafter. The difference between sexes in cause-specific mortality was smaller than in the general population. Cause-specific mortality differed significantly from the general population, with reduced mortality from neoplasms and external causes, but ageing individuals with mild ID had similar mortality patterns to the general population. The disparities in the cause-specific mortality between younger people with ID and the general population fade with advancing age, producing similar health risks. In preventative work, special attention should focus on common diseases and accidents in the community.

Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias.

Our objectives were to investigate the utility of the Hachinski Ischemic Score (HIS) in differentiating patients with pathologically verified Alzheimer's disease (AD), multi-infarct dementia (MID), and "mixed" (AD plus cerebrovascular disease) dementia, and to identify the specific items of the HIS that best discriminate those dementia subtypes. Investigators from six sites participated in a meta-analysis by contributing original clinical data, HIS, and pathologic diagnoses on 312 patients with dementia (AD, 191; MID, 80; and mixed, 41). Sensitivity and specificity of the HIS were calculated based on varied cutoffs using receiver-operator characteristic curves. Logistic regression analyses were performed to compare each pair of diagnostic groups to obtain the odds ratio (OR) for each HIS item. The mean HIS (+/- SD) was 5.4 +/- 4.5 and differed significantly among the groups (AD, 3.1 +/- 2.5; MID, 10.5 +/- 4.1; mixed, 7.7 +/- 4.3). Receiver-operator characteristic curves showed that the best cutoff was < or = 4 for AD and > or = 7 for MID, as originally proposed, with a sensitivity of 89.0% and a specificity of 89.3%. For the comparison of MID versus mixed the sensitivity was 93.1% and the specificity was 17.2%, whereas for AD versus mixed the sensitivity was 83.8% and the specificity was 29.4%. HIS items distinguishing MID from AD were stepwise deterioration (OR, 6.06), fluctuating course (OR, 7.60), hypertension (OR, 4.30), history of stroke (OR, 4.30), and focal neurologic symptoms (OR, 4.40). Only stepwise deterioration (OR, 3.97) and emotional incontinence (OR, 3.39) distinguished MID from mixed, and only fluctuating course (OR, 0.20) and history of stroke (OR, 0.08) distinguished AD from mixed. Our findings suggest that the HIS performed well in the differentiation between AD and MID, the purpose for which it was originally designed, but that the clinical diagnosis of mixed dementia remains difficult. Further prospective studies of the HIS should include additional clinical and neuroimaging variables to permit objective refinement of the scale and improve its ability to identify patients with mixed dementia.

Long-term survival and predictors of mortality in Alzheimer's disease and multi-infarct dementia.

Long-term survival was examined for 218 patients with Alzheimer's disease (AD) and 115 patients with multi-infarct dementia (MID). The 14-year survival rate for AD was 2.4% versus an expected rate of 16.6%, and for MID 1.7% versus 13.3% expected. MID showed a more malignant natural course than AD. Men carried a less favourable survival prognosis than women, both in AD and MID: the relative risk of dying for women was half that for men in both diseases. In MID, advanced disability indicated a relative risk of dying over twice as high. In both diseases the risk of death was substantially higher in the event of occurrence of primitive reflexes.

Brain methionine- and leucine-enkephalin receptors in patients with dementia.

Brain [3H]Met- and [3H]Leu-enkephalin binding was studied in patients with Alzheimer's disease (AD) and vascular dementia (VD), and in age-matched controls. Brain areas investigated were the internal and external globus pallidus, amygdala, hippocampus and temporal cortex. In AD, the binding of both enkephalins decreased in all brain areas examined, except in the external globus pallidus for both enkephalins and in the internal globus pallidus for leucine-enkephalin. Scatchard analysis of amygdaloid samples showed a decrease in the number of receptors (Bmax) without any change in their affinity (Kd). In patients with VD, no significant changes in enkephalin binding were seen. Thus, in AD, enkephalin binding (mainly reflecting delta opioid receptor subtype) is decreased, especially in limbic areas.

Hepatitis B carriers in a centre for the mentally retarded in Finland and immunogenicity of hepatitis B vaccine.

The institutionalized population and staff in a centre for the mentally retarded were tested retrospectively, and 1.6% hepatitis Bs antigen and 0.6% hepatitis Be antigen carriers were found among persons with mental retardation. The 40 subjects, residents and staff, with most risk of acquiring hepatitis B were given vaccination. The immunogenicity of the H-B-Vax vaccine was followed up prospectively and, in 7.5% of the vaccinated persons, even re-vaccination gave an unsatisfactory result.

Neuronal loss in the substantia nigra in patients with Alzheimer's disease and Parkinson's disease in relation to extrapyramidal symptoms and dementia.

Regional neuronal loss in the substantia nigra (SN) was studied in relation to extrapyramidal symptoms and dementia in 27 patients with Alzheimer's disease (AD), 12 patients with idiopathic Parkinson's disease (PD) and 18 controls. Four areas of the right SN were investigated at the level of the caudal red nucleus. In AD the number of neurons were reduced to 97%, 79%, 83% and 78% of the control values from the medial to lateral SN respectively. The number of lateral neurons showed a negative correlation with the severity of rigidity and hypokinesia. The degree of dementia did not have a significant correlation with nigral neuronal counts. In PD, the number of neurons was markedly reduced in all parts of the SN, most pronouncedly in the lateral part. The number of lateral neurons showed a negative correlation with the severity of rigidity and hypokinesia, whereas tremor had a positive correlation. The degree of dementia of the patients had a negative correlation with the number of medial neurons, suggesting that degeneration of the nigrostriatal neurons may contribute as a subcortical component to dementia in PD patients.

A comparison of brain choline acetyltransferase activity in Alzheimer's disease, multi-infarct dementia, and combined dementia.

Brain choline acetyltransferase (ChAT) activity was determined in 43 patients with Alzheimer's disease (AD), 14 with multi-infarct dementia (MID), and 15 with combined dementia (CD) and in 53 age-matched controls. The activity of ChAT declined in the hippocampus, temporal and frontal cortex in patients with AD and CD compared to the controls. In the AD group the reduced activity of ChAT in all brain areas was associated with a greater number of cortical neurofibrillary tangles. The degree of dementia had a negative correlation with the activity of ChAT in the frontal cortex in both AD and CD patients. The activity of ChAT in the temporal cortex of CD patients was negatively associated with the cortical tangle counts. In contrast, the activity of ChAT and MID patients was not essentially different from that of the controls. Neither did the various clinical and neuropathological variables show any significant correlation with ChAT activity in MID patients. Thus, in this study the reduction in the activity of ChAT seems to be associated with Alzheimer-type pathology but not with dementia due to vascular changes.

Alzheimer's disease: neuropathological correlates of cognitive and motor disorders.

Correlations between clinical symptoms and changes in brain neuropathology were investigated in 34 patients with Alzheimer's disease, who were compared with 17 non-demented, age-matched controls. The patients were originally found in a community survey of dementia and were followed up prospectively until death. A highly significant correlation emerged between the severity of dementia and the numbers of plaques and tangles in the material as a whole, but no essential difference was found between severely and less severely demented patients. Low brain weight correlated highly with many clinical symptoms and signs and the severity of dementia. A multiple regression model consisting of plaques and tangles in amygdala, gyrus frontalis medius, gyrus angularis, and gyrus temporalis medius, plaques of gyrus rectus, tangles of the hippocampus, gyrus precentralis and gyrus cinguli together with brain weight, emerged to link dementia to neuropathological changes at the level of maximum significance. Dyskinetic movements were associated with damage of several brain areas, implying a multiple etiology.

Senile dementia of the Alzheimer type treated with aniracetam: a new nootropic agent.

Forty-four patients with senile dementia of the Alzheimer type were randomly allocated into double-blind treatment with either aniracetam (RO 13-5057) 1 g or placebo daily for 3 months. Neurological examinations were made before and after treatment and psychometric tests were performed before and after 1 month's and after 3 month's treatment. Treatment was interrupted due to occurrence of confusion in four cases in the aniracetam group and in one case in the placebo group. During treatment, an improvement was seen in several cognitive tests, especially those associated with memory, but this improvement occurred in the placebo as well as in the aniracetam-treated group. In clinical evaluation no difference was seen in efficacy between the two treatment groups.

Survival and cause of death in Alzheimer's disease and multi-infarct dementia.

Survival and causes of death of 218 patients with Alzheimer's disease (AD) and of 115 patients with multi-infarct dementia (MID) were examined. The patients were originally found in a community-based epidemiological survey of dementia, and all patients with AD or MID alive on the prevalence day were included. The 6-years survival rate for AD was 21.1% vs. the expected rate 48.5%, that for MID 11.9% vs. 45.2% expected. A comparison of relative survival rates suggested that MID carries a less favorable survival prognosis than AD. The mean durations were: AD 5.7 years and MID 5.2 years; median duration being 5 years in both diseases. The excess mortality in both AD and MID was independent of age. In AD, the survival rate decreased with increasing severity of dementia, while in MID the mortality was the same regardless of the severity of the dementia. The dementia disorder was the underlying cause of death in 68% of AD patients, and in 38% of MID patients, bronchopneumonia being the most frequent immediate cause of death in both groups. As a cause of death, acute cerebrovascular accidents occurred more often in MID patients than in the general population of comparable age. Malignant diseases were less frequent as a cause of death in both dementia groups than in the general population.

Brain dopamine D-1 receptors in senile dementia.

Brain dopamine D-1 binding sites were studied by using [3H]flupenthixol in 4 brain regions of 44 senile patients with neuropathologically verified organic dementia and 28 age-matched controls. The D-1 binding sites were decreased in the substantia nigra and nucleus accumbens in patients with Alzheimer's disease, while no change was found in multi-infarct or combined dementia. The striatal D-1 binding sites were unchanged in all groups of patients. Only a few correlations between various clinical and post-mortem variables and the [3H]flupenthixol binding of the dementia patients were found. The findings of this study indicate that there is reduction of brain D-1 binding sites in patients with Alzheimer's disease.

Inducement of therapeutic amenorrhea in mentally retarded women: two-year follow-up study.

Therapeutic amenorrhea was induced in 44 moderately to severely mentally retarded women, aged 15 to 44 years. Subjects received lynestrenol or norethisterone in an identical oral dose of 5 mg daily. After 24 months, total amenorrhea was found in 70% of the women in the lynestrenol group and in 76% of those in the norethisterone group.

Brain dopamine D-2 receptors in senile dementia.

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 of 3H-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 of 3H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between 3H-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 mentally handicapped child and family crisis.

The defences of family members were studied in order to observe the reactions of the family when faced with a dysfunction in one of its members. Thirty families with a mentally handicapped child were studied, and the attitudes of parents, grandparents and siblings towards the handicapped child were examined. The data showed that the birth of a mentally handicapped child interrupts the normal life-cycle of the family, leading to a crisis. The first reaction in the parents was most often found to be denial, but ultimately adaptation was demonstrated in nearly 80% of the parents. Many of the siblings' and grandparents' reactions differed significantly from those of the parents, being more positive than those of the latter.

Validity of clinical diagnosis in dementia: a prospective clinicopathological study.

With neuropathological diagnosis as the point of reference, the accuracy of clinical diagnosis was studied in a series of 58 demented patients. Alzheimer's disease and multi-infarct dementia were recognised with sensitivities and specificities exceeding 70%, whereas combined dementia as a separate group was relatively unreliably diagnosed. The value of Hachinski's Ischaemic Score in differentiating between Alzheimer's disease and vascular dementias was demonstrated. Its performance was to some extent improved by assigning new weights to the items. In a logistic regression model, fluctuating course, nocturnal confusion, and focal neurological symptoms emerged as features with the best discriminating value, and helped to diagnose correctly 89% of the Alzheimer and 71% of the vascular dementia patients.

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.

Extrapyramidal signs in Alzheimer's disease.

The occurrence and type of extrapyramidal signs were investigated in 143 patients with dementia of the Alzheimer type. Only 8% of the patients were free of extrapyramidal signs. The most common type of extrapyramidal involvement was a rigid, hypokinetic, and hypomimic pattern. Resting tremor was rarely encountered. Dyskinetic signs, mostly orofacial, were seen in 17%. These observations suggest that in most patients with advanced Alzheimer's disease, there is a striatal dopaminergic hypofunction, appearing clinically as hypokinesia and rigidity. However, some patients exhibit predominantly dyskinetic signs, implying more complex basal ganglia dysfunction.

Epidemiology of dementia in a Finnish population.

An epidemiological study of dementia was carried out in the city of Turku (population 164,568) in Finland. A total of 421 patients with moderate to severe dementia were found. Degenerative dementia, i.e. presenile and senile dementia, was present in 218 patients (51.8%), and in 152 patients (36.1%) the dementia was associated with arteriosclerosis, including multi-infarct and combined dementia. The prevalence rate of dementia, all types, was 256 per 100,000 population, and 1,961 per 100,000 population over 65 years old. The age-specific prevalence rates of dementia increased with advancing age from 0.1% in the age group 55-64 years to 11% in the age group over 85 years. The peak annual incidence rate for all types of dementia was 58 per 100,000 population, and 447 per 100,000 population over 65 years old. Both prevalence and incidence figures suggested a female preponderance in dementia of degenerative origin and in dementia with associated arteriosclerosis.