One of the more active areas of clinical research related to dementia and Alzheimer's disease is the attempt to identify cognitive, behavioral, and biological changes that occur during a "preclinical" phase that precedes the manifestation of the overt dementia syndrome. This research is based on current conceptualizations of Alzheimer's disease, which suggest that the neuropathology of the disease gradually accumulates, causing the insidious onset of cognitive dysfunction. As neuropathological changes proceed, cognitive dysfunction increases to a level where it becomes unambiguous and disruptive to daily functioning. It is at this point that the clinical diagnoses of dementia and Alzheimer's disease can be made with some certainty. Studies examining cognitive changes in the preclinical phase of Alzheimer's disease usually identify decline in episodic memory (the con-textually rich memory of specific events and places a person experiences) as the earliest manifestation of the disease. Memory decline in the face of relatively intact general cognition (e.g., as assessed with a brief mental status examination) and day-to-day functioning defines a condition widely known as amnestic mild cognitive impairment.
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