Clinical diagnosis of Alzheimer's disease is most accurate when the patient presents with frank progressive cognitive decline. However, it is likely that signs and symptoms of Alzheimer's disease become evident after the pathophysiological processes of the disease have become established. A convenient early marker for Alzheimer's disease would be useful for identifying persons at risk for developing the illness. Such markers will be essential for early intervention when effective treatments become available. Numerous studies have indicated that the principal risk factors for developing Alzheimer's disease are age and having a first-degree relative with Alzheimer's disease. Thus the very old individuals and first-degree relatives of Alzheimer's disease patients constitute high-risk groups and should be expected to develop Alzheimer's disease at a more rapid rate than the general population. Members of these high-risk groups are therefore appropriate subjects for testing hypotheses concerned with detection of early Alzheimer's disease. A significant portion of Alzheimer's disease patients have elevated serum levels of the acute phase reactants a-antichymotrypsin and a- macroglobulin. In particular, elevated serum levels, of a- antichymotrypsin are associated with clinical Alzheimer's disease. It is proposed to compare serum acute phase reactant levels of age-matched subjects who fall into one of the following groups: Non-demented very old (age > 85); Early dementia; -Dementia; First-degree relatives of Alzheimer's disease patients. It is also proposed to determine if levels of acute phase reactants are correlated with neuropsychological markers of dementia in these subjects categories. Serum acute phase reactant levels of dementia in these subject categories. Serum acute phase reactant levels will be measured at yearly intervals for all patients to determine both how they change with time and if changes are associated with a decrease in cognitive performance. For those subjects in the study who come to autopsy, ante-mortem serum acute phase reactant levels will be compared to neuropathologic findings to determine the relationship of serum acute phase reactant levels to autopsy-proven Alzheimer's disease.
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