ISSN:0304-324X    

DOI:10.1159/000212863

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0304-324X    

DOI:10.1159/000212864

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

There are two main clinical manifestations of the aging brain, which appear to be independent of any disease process, namely adaptability and general slowing. Impaired adaptability depends in part on poor function of the homeostatic mechanisms. General slowing affects all levels of nervous activity and can be measured in various ways. Research relevant to the clinical problem is reviewed and evaluated.

ISSN:0304-324X    

DOI:10.1159/000212865

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Even in nonfamilial cases of dementia there is some evidence of a genetic factor. This may be linked to defective expression of neurofilament protein and also abnormal phosphorylation of cytoskeletal proteins. In this respect there may be a link with accumulation of tangles and amyloid which have some degree of homology. It may be speculated that neurons containing tangles or undergoing granulovacuolar degeneration would not be able to release trophic factors and that transneuronal degeneration would result. However, the environmental or aetiological factors associated with Alzheimer’s disease are not known. Although there has been a failure to transmit Alzheimer’s disease to primates, it is possible that as in postencephalitic Parkinson’s disease virus may be implicated at some stage in the pathogenesis. Finally, free radical formation has been considered as an alternative mechanism for death of large neurons within the CNS. Although tangles are found in several other dementing conditions (e.g. dementia puglistica, Parkinson-dementia complex of Guam), Alzheimer-type plaques and tangles are not invariably found in cases of cognitive deficit. For example, in dementia of Parkinson’s disease there is a low neuritic plaque count and normal population of tangles. In addition, memory loss is not necessarily associated with defects in the cholinergic system and/or loss of nucleus basalis nerve cells. We have proposed that damage to or loss of cortical cells may be a more general finding in dementing

ISSN:0304-324X    

DOI:10.1159/000212866

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

During aging there are several structural, functional and biochemical alterations, including changes in macromolecular composition and turnover. Regulation of gene expression, DNA and RNA synthesis, total poly(A)+ and poly(A)–– RNA contents, qualitative and quantitative changes of synaptosomal plasma membrane proteins, diminished plasticity, loss of synapses, lower rate of axoplasmic transport, impairment of antioxidant and bioen-ergetic systems seem to be involved in the aging process of nervous system.

ISSN:0304-324X    

DOI:10.1159/000212867

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The lipid composition of cell plasma membranes reflects a steady-state between accumulation of serum lipids, predominantly cholesterol, and intracellular lipid synthesis and degradation. In the aging tissue this subtle balance is impaired with a net accumulation of cholesterol and other rigidifying lipids such as sphingomyelin in the membrane. As a consequence, most membrane processes, including ion transports in neuronal tissues, are slowed down. In principle, it is possible to rectify such adversative processes in vivo by increasing the level of specific phospholipids and glycerides in the serum.

ISSN:0304-324X    

DOI:10.1159/000212868

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0304-324X    

DOI:10.1159/000212869

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Reductions of the levels of transmitter substances and of the activities of enzymes involved in their synthesis have been demonstrated in the aging brain. The sensitivity to the aging process varies for different transmitters and brain regions. Dopamine neurons are more age-sensitive than most other neurons investigated. The metabolism of monoaminergic neurotransmitters is enhanced in the aging brain, as evidenced by increased metabolite/neurotransmitter ratios, perhaps to compensate for the loss of transmitter. In various types of dementia, including Alzheimer’s disease (AD) and senile dementia of Alzheimer type (SDAT), several neurotransmitter indices are reduced, as compared to age-matched controls. Moreover, a decrease in neurotransmitter metabolites suggests that compensatory mechanisms are insufficient. No correlation could be found between the neurotransmitter changes and the histological changes characteristic of AD (senile plaques and neurofibrillary tangles). Neither could any relationship between multiple infarctions and neurotransmitter indices be detected. Recently observed changes in the lipid composition of the white matter, indicating demyelinization, in the brains of patients with AD/SDAT, emphasize the multifactorial aspects of dementia. Taken together, the data underline the difficulties in drawing clear demarcation lines between normal and pathological aging and between different subgroups of dementia. Despite the obvious difficulties, future therapeutic efforts should aim at substitution for the neurotransmitter deficiencies. Preventive measures have to await the clarification of the mechanisms underlying neural degeneration. Studies of the toxicity of oxygen and of autoxidation products are among the areas of research that may help to shed light on this proble

ISSN:0304-324X    

DOI:10.1159/000212870

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Disorders of neurotransmitter balance are observed in Parkinson’s disease, pharmacotoxic psychosis and depression. The dopamine-serotonin ratio is reduced to about 20% in Parkinson and pharmacotoxic patients in the caudate nucleus and in the substantia nigra. The serotonin content in these brain areas is lowered only to about 50% in comparison to that of the control, whereas the dopamine level is reduced to 85% in Parkinson patients. This dopamine deficiency has been substituted by exogenous supply of L-dopa in combination with decarboxylase and monoaminooxydase inhibitors. First evidence is presented that L-dopa can be replaced, at least partially, by iron in form of a ferriascorbate complex. This iron compound improves the symptoms of Parkinson’s disease to almost the same extent as L-d

ISSN:0304-324X    

DOI:10.1159/000212871

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

A morphometric analysis of neuronal loss during normal aging was performed in the nucleus basalis Meynert complex of the basal forebrain (Nbm) (nucleus septi medialis, nucleus of Broca’s diagonal band, nucleus basalis) and the ciliary ganglion, a peripheral cholinergic structure, in patients free of neurological and psychiatric illness. As a basis for morphometric evaluation of the Nbm complex, a three-dimensional reconstruction of this complex structure was made. Neuronal counts in the Nbm complex and the ciliary ganglion remained stable up to the age of 60 or 50 years, respectively. After this age the number of neurons declined moderately in ciliary ganglion in all cases studied as well as in the Nbm complex in some cases (–20 and –25%, respectively, at about 90 years of age). In 3 out of 8 cases older than 60 years, neuronal counts in the Nbm complex were not reduced, so that no significant decline in neuronal number is apparent from the mean values of the 17 cases studied. No age-related changes were found in the neuronal distribution amongst the different subgroups of Nbm neurons using the alternative nomenclature of Mesulam et al. [J. comp. Neurol. 214: 170–197, 1983]. Our results provide no evidence that the cortical cholinergic projection system and peripheral cholinergic neurons might be especially vulnerable during normal aging. The severe degeneration of the cholinergic cortical projection system in SDAT is probably caused by mechanisms different from those acting during normal aging.

ISSN:0304-324X    

DOI:10.1159/000212872

出版商:S. Karger AG    

年代:1987

数据来源: Karger