These findings are consistent with the hypothesis that NPs are among the earliest neuropathological lesions in AD. Even very mild or questionable dementia is associated with increased density of neocortical NPs that do not distinguish between clinically questionable vs definite dementia.

The high rate of major depressive episodes that occur after the onset of cognitive impairment among patients with Alzheimer's disease (the majority of whom had no premorbid history of major depression), common emergence in the early stages of dementia when symptoms of cognitive impairment are least likely to contribute to the syndromal diagnosis of major depression, and differences in the clinical presentations of the major depressive episodes of Alzheimer's disease patients and nondemented elderly comparison subjects, all support the validity of the major depressive syndrome of Alzheimer's disease. Our findings suggest that the major depressive syndrome of Alzheimer's disease may be among the most common mood disorders of older adults.

Despite the limitation of a cross-sectional design, our initial findings suggest that there is a strong association between medical comorbidity and cognitive status in AD. Optimal management of medical illnesses may offer potential to improve cognition in AD.

Some NFTs are present in the entorhinal cortex and hippocampus of most elderly individuals irrespective of their cognitive status, but the density of NFTs increases as a function of dementia severity.

These results raise the possibility that the varied associations observed between diabetes and AD may be specific to as yet ill-defined subgroups of dementia and diabetic patients or may be more characteristic of younger patients than of those who survive to a mean age of 84 years. Future studies are encouraged to examine a variety of other characteristics such as age that may interact with diabetes affecting the incidence of AD.

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Use of systemic antibiotics is prevalent in the treatment of patients with end-stage dementia, despite the limited utility and discomfort associated with the use of these agents. That patients with severe dementia and those with milder cognitive impairment received similar treatment may be contrary to good clinical practice, given the poor prognosis of patients with severe dementia.