Alzheimer's disease. A critical review

Clinical and neuropathological findings in a 51-year-old woman by Alois Alzheimer (1) led to a description of the disorder which Kraepelin (2) named Alzheimer's disease (AD). In this progressive dementia disorder the senile plaques and fibrillary tangles found at brain autopsy are the diagnostic hallmarks. As the same type of neuropathological changes are found in dementias of senile age, these disorders are named senile dementia of the Alzheimer type (SDAT). The two forms are often combined into one group, the Alzheimer dementias, (AD/SDAT) and, according to the DSM-III, classified as primary degenerative disorders (PDD). However, it must be emphasized that there is no scientific basis for sampling the two forms, the diagnoses of both AD and SDAT are exclusive. Several hypotheses are being proposed as to the etiology of AD/SDAT. Genetic factors, aluminium or other toxic factors, immunological disturbances, disturbed glucose metabolism, deficiency of essential nutrients, and stress, are some of the lines followed when seeking the etiology. The pathogenesis of the disorder involves not only structural changes but also neurochemical disturbances and neuroendocrine dysfunction, findings which are related to the behavioural disturbances seen in the disease. At present there are no reliable biological markers for AD/SDAT. Clinical investigations together with laboratory data and brain imaging support the assumption of several sub-groups within the Alzheimer type dementias. The neurochemical findings made in AD/SDAT have constituted the basis for formulating pharmacological treatment strategies. Drugs affecting the cholinergic and monoaminergic systems have been used, as well as neuropeptides and similar drugs. Gangliosides and phosphatidylserine have also been tested in clinical trials. Hitherto, this treatment has not been as successful as expected. Cholinergic drugs have given a marginal effect on memory functions. Emotional disturbances and disturbed motor performance have to some extent been influenced by the use of selective 5-hydroxytryptamine reuptake blockers and L-dopa. Whether this treatment is of clinical importance must be further investigated. Interesting neuropathological and neurochemical research is being conducted on AD/SDAT. However, clinical research aiming at delimiting homogeneous subgroups of dementia has not kept in step with neurobiological research. More effort must be put into clinical research if therapeutic progress is to be achieved.