ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05865.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Our knowledge of the etiology and pathogenesis of Alzheimer's disease is limited. The most conspicuous changes seen in the brain are deposits of insoluble proteins in both extracellular and intraneuronal locations. The extracellular deposits consist primarily of a specific A4 amyloid protein. The significance of these deposits remains to be determined, as they are often found in the cerebral cortex of non‐demented elderly persons. More telling is the gradual accumulation of insoluble fibrous material within some neurons that consists mainly of abnormally phosphorylated tau protein. Six stages of increasingly severe cortical destruction can be distinguished. Stages I and II are characterized by neurofibrillary changes that are largely confined to the transentorhinal region, whereas stages III and IV are marked by severe involvement of both the entorhinal and transentorhinal regions. Isocortical destruction occurs during stages V and VI. This progression in cortical pathology correlates with the gradual worsening of clinical symptom

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05866.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Four genes have thus far been implicated in the etiology of Alzheimer's disease (AD). A series of mutations in the amyloid precursor protein (APP) gene on chromosome 21, which cause disease with a typical onset of 55 years of age, have been described. These include mutations at APP670/671, APP692, and APP717. The ε4 allele of the apolipoprotein E (ApoE) gene on chromosome 19 is positively associated with disease, whereas the ε2 allele is usually negatively associated with disease. Mutations in the S182 gene on chromosome 14 seem to cause disease with an onset age of<50 years and mutations in a gene on chromosome 1 (S182 Like Protein: S182LP) cause disease with variable onset. These genetic findings are reviewed within the framework of the amyloid cascade hypothesis of AD etiology and pathogenesis. The occurrence and effects of the mutations in APP and the fact that the ε4 allele of ApoE are genetic risk factors point to the hypothesis that the extracellular deposition of β‐amyloid is the key initiating event in the pathogenesis

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05867.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Glucose metabolism in the brain has an important influence on many normal cellular processes. It contributes to the synthesis of acetylcholine, glutamate, aspartate, γ‐aminobutyric acid, glycine, and ATP production (the driving force behind almost all cellular and molecular activity). Neuronal glucose metabolism is controlled antagonistically by insulin and cortisol. Desensitization of the neuronal insulin receptor causes abnormalities in oxidative energy metabolism. During normal aging, the cerebral energy pool is slightly diminished, but its level increases after stressful events. In age‐related sporadic late‐onset dementia of the Alzheimer type (SDAT), glucose metabolism and formation of cellular energy are severely reduced. Desensitization of the neuronal insulin receptor seems to be an early event in the pathogenesis or even etiology of SDAT causing disturbances in oxidative glucose metabolism and energy failure in insulin‐sensitive brain structures. These abnormalities appear to induce a cascade of disturbances that leads to abnormal APP processing and amyloid formation, membrane damage, and neuron

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05868.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

It has long been assumed that widespread changes in postsynaptic neurotransmitter receptor function are not a feature of the disrupted neurotransmission seen in the brains with Alzheimer's disease (AD). However, recent evidence from postmortem brain and fibroblast studies suggests that both the neurotransmitter receptor/G‐protein‐modulated adenylyl cyclase and the phosphatidylinositol hydrolysis signal transduction cascades are disrupted in AD. Such disruptions may severely limit the functional integrity of key receptor types and undermine pharmacological attempts to ameliorate disease symptomatology through neurotransmitter replacement strategies. The involvement of some signalling mechanisms in the regulation of β‐amyloid precursor protein metabolism suggests also that disrupted signal transduction may exacerbate AD pat

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05869.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Many epidemiological studies of Alzheimer's disease (AD) have been conducted. This review discusses the most recent findings in relation to the possibilities of prevention of this disease. Data on the diagnostic validity are also reported. The primary prevention of AD is hampered by limitations in the knowledge and understanding about its risk factors. Among the factors that have been investigated, only age, familial aggregation, and apolipoprotein E gene‐e4 allele are definite risk factors both for early‐ and late‐onset AD. However, many of the possible and putative risk factors, if definitely confirmed, can be prevented or controlled. Secondary prevention is not currently practicable as valid predictive tests and efficacious treatment are lacking. In contrast, much data is available to support tertiary prevention interventions, such as better planned patient

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05870.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Classification of dementia involves the recognition of its presence, followed by the differential diagnosis of its cause. Informant‐based methods for dementia detection can be highly sensitive, even when cognitive impairment is mild. Alzheimer's disease (AD) is by far the leading cause of dementia; standardized clinical criteria result in high diagnostic accuracy rates. Classification of other dementing disorders is less satisfactory, particularly because there is frequent clinical and pathological overlap with AD. After AD, the most common causes of dementia are vascular dementia and dementia in persons with Parkinson's disease. Less common dementias include progressive supranuclear palsy, Huntington's disease, Pick's disease, Creutzfeldt‐Jakob disease, and inherited metabolic disorders, most of which are extremely rare. Identifying the cause of dementia is important because some forms can be treated with currently available therapies. In instances involving genetically transmitted disease, genetic testing and counseling of family members may be advisa

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05871.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

During the last decade, senile dementia and the presenile disease that was named after Alois Alzheimer have been considered a single entity called Alzheimer's disease (AD). This same decade has witnessed the development of many diagnostic tools, such as CT, MRI, and SPECT imaging, that have made possible the systematic analysis of symptoms of brain disorders. With the aid of these sophisticated techniques, it is possible to divide the disorder into clinically relevant subgroups, one of which corresponds to the disease first described by Alzheimer. The disease exists in sporadic and familial forms, and in subgroups of these two basic types. Because the heterogeneity of AD is incontestable, it is time to reconsider the current use of the term “Alzheimer's disease.” Because it labels different subgroups whose characteristics are often markedly different, the term “Alzheimer syndrome” appears to be more appr

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05872.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

In Sweden, as in many other industrial countries, the majority of patients with symptoms of dementia are initially evaluated by a general practitioner (GP), and many do not receive a follow‐up assessment by a specialist. Accordingly, GPs play a vital role in identifying patients with possible dementia and undertaking additional diagnostic procedures. Currently, however, the ability of most GPs to perform assessments for dementia is limited. It is important that tests to confirm the presence of dementia be performed uniformly, irrespective of the specialty of the examining physician. Once a diagnosis of dementia has been established and appropriate living arrangements for the patient have been made, the GP should continue to monitor the patient's health status. In Sweden, “dementia teams” of health care professionals have been successful in providing a consistently high level of care to patients with dementia, reducing the incidence of hospitalization for acute il

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05873.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

In the preclinical stage of Alzheimer's disease (AD), studies of asymptomatic mutation carriers have identified impairments in episodic memory. Other cognitive functions show no or slight impairment suggesting that preclinical AD is a unifunctional cognitive syndrome; the brain is affected selectively and predominantly in the medial temporal structures. In the early clinical stage, deficits occur in episodic memory, verbal abilities, visuospatial functions, attention, and executive functions. AD becomes a multifunctional cognitive syndrome and the brain's association cortices are affected. Nevertheless, sensory‐motor performance and procedural memory seem to be intact and only slight impairment may be seen in primary memory. In advanced AD, cognitive dysfunction including deficits is global in primary memory, although sensory‐motor performance may be well preserved. The brain's association cortices are severely affected. The sequence of cognitive decline, from unifunctional to global deficits, conforms to the three‐stage development of neurofibrillary tangles described by Braak and

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1996.tb05874.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY