U. K. Rinne

Oxygen toxicity protecting enzymes in Parkinson's disease: Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus

Oxygen-derived toxicity has been suggested as being involved in the pathogenesis of Parkinsons disease. Superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase provide the enzymatic defence against oxygen toxicity. The activities of these enzymes were measured in peripheral blood leucocytes, cerebrospinal fluid and in different brain regions from patients with idiopathic Parkinsons disease and from controls. There was no indication of a generalized defect in any of these enzymes in Parkinsons disease. The brain activities of catalase, glutathione peroxidase and glutathione reductase were also comparable to those of the controls. An increased superoxide dismutase-like activity was observed in several regions of parkinsonian brains, including the temporal cortex, thalamus and red nucleus. However, the most pronounced increase occurred in the substantia nigra and basal nucleus. This may be due to an increase of the superoxide dismutase activity or be a result of the presence of a compound with superoxide dismutase-like activity, and may reflect the involvement of radical-induced cell damage in the pathogenesis of Parkinsons disease.

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

ABSTRACT Survival and causes of death of 218 patients with Alzheimers 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.

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.

EPIDEMIOLOGY of PARKINSON'S DISEASE IN FINLAND

This investigation was conducted to clarify the epidemiology of Parkinsons disease in Finland. A community survey was made in a selected area in southwest Finland in addition to an analysis of Finnish mortality statistics for Parkinsons disease. the annual mortality rate from Parkinsons disease was found to average 2 per 100,000 population. Almost 70 per cent of the deaths occurred between 65‐79 years of age. the total and age‐specific mortality rates for males were greater than those for females whereas the proportionate mortality rates were almost identical. This was considered to indicate that suggestions of greater male prevalence, based on mortality statistics, do not appear justified. On prevalence day, Dec. 31st, 1971, 484 patients with Parkinsons disease (of which 444 were personally examined) lived in the area of investigation (population 402,988), the prevalence rate being 120.1 per 100,000 population. the highest annual incidence rate was 16.6 per 100,000 population. the age‐specific prevalence rates showed a rapid increase after the 50th year of age. the greatest prevalence was shown by the age group 70–79 years of age in which almost 0.8 per cent of the population are affected. Age‐specific incidence rates also displayed an increase after the 50th year of age. the greatest incidence was observed in the age group 70–79 years of age in which almost 1 per 1,000 of the population are annually affected by the disease. A difference between the sexes was demonstrable in the prevalence and incidence rates showing greater values for females, but in the age‐specific frequencies the differences were reduced. This probably reflects the difference between the age structures of the male and female populations, suggesting that both sexes have a similar risk of being affected by the disease. the permanent age structure shown by idiopathic patients in comparison with previous investigations as well as the increased mean age and proportionate decrease of postencephalitic patients was found to be in disagreement with the cohort theory according to which all parkinsonian patients are previously victims of encephalitis lethargica.

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. Alzheimers 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 Hachinskis Ischaemic Score in differentiating between Alzheimers 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.

DEMENTIA IN PARKINSON'S DISEASE

The occurrence of dementia in patients with Parkinsons disease was studied in a Parkinsonian population consisting of all traceable patients residing in a defined area. the prevalence of dementia was found to be 29 per cent in 444 patients studied. the frequency of dementia increased with advancing age and the patients showing signs of clinical arteriosclerosis were more often demented than the patients without arteriosclerosis. There was, however, an evident association between the stage of the disease and the frequency of dementia. the most severely disabled patients displayed dementia more often than the mildly affected, both among the patients with and without arteriosclerosis. the demented patients showed significantly more severe rigidity and hypokinesia when compared with the non‐demented. Increasing severity of rigidity and hypokinesia, in particular, was found to have a positive correlation with the degree of dementia. the association between dementia and the degree of motor involvement is considered to suggest the role of subcortical structures in the pathophysiology of dementia in Parkinsons disease.

Essential tremor in a Finnish population.

A two‐phase epidemiological study of essential tremor was carried out by investigating a rural population aged over 40 years in 2 municipalities in southwestern Finland. In the first phase, the subjects answered a questionnaire as to whether they had experienced tremor during the month preceding the inquiry. In the second phase, the persons who had tremor often or fairly often, were examined clinically. The total prevalence of essential tremor, calculated on the basis of clinically established cases, was 55.5‰ of the population aged over 40 years. The disease became more prevalent with advancing age and was, with the exception of the oldest age‐group, more common in men than in women.

Changing epidemiology of Parkinson’s disease in southwestern Finland

Objective: Investigation of the epidemiology of PD in southwestern Finland in 1992 (population 196,864), including urban and rural areas, with a comparison with a similar study, done in the same area in 1971, to evaluate the temporal pattern. Methods: Community-based method of patient ascertainment with personal investigation of cases. Results: The age-adjusted prevalence (to the Finnish general population in 1991) was 139 per 100,000 population in 1971 and 166 in 1992. Prevalence ratio for PD in men versus women was 1.2 (NS) in 1971 and 1.7 in 1992 (p < 0.001); in the rural versus urban populations the prevalence ratio was 0.8 (NS) in 1971 and 1.3 in 1992 (p = 0.013). The age-specific prevalence rates showed a male preponderance in all age groups in 1992 and a rural preponderance in the age groups over 60 years. In 1992, compared with 1971, the male and rural preponderance occurred in the age groups over 70 years. The age-adjusted incidence was 15.7 per 100,000 population in 1971 and 14.9 in 1992. Relative risk for PD in men versus women was 0.9 (NS) in 1971 and 1.9 (p < 0.001) in 1992, and in rural versus urban populations 1.4 (p = 0.093) in 1992. Conclusions: A very significant male and a significant rural predominance, not seen in 1971, suggests a possible environmental causative factor, perhaps more frequent in the rural environment, associated with PD. Men may be either more exposed to it or more susceptible to its effects than women.

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 Alzheimers 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.

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

Long‐term survival was examined for 218 patients with Alzheimers 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.