Alzheimer's patients can experience excess disability from delirium or toxic or metabolic encephalopathies. Even though demented patients are at higher risk than intact patients for delirium and toxic or metabolic encephalopathies, the symptoms often go unrecognized. This is in part because diagnosis is confounded by the overlap in symptoms between irreversible dementia and reversible toxic or metabolic encephalopathies. One critical difference is in the clinical course; Alzheimer's disease is characterized by an insidious onset and a gradual decrement in function, while delirium and other encephalopathies can be associated with changes over shorter periods of time. What is needed to facilitate case identification is an objective method for monitoring the cognitive functioning of Alzheimer's patients. This proposal details a program of research consisting of three studies designed to investigate delirium and related disorders in Alzheimer's patients and to clarify diagnostic methods. Study I involves the application of a statistical technique to repeated assessments of cognitive functioning in Alzheimer's patients to define the normal limits of within-patient variability in cognitive performance in patients with uncomplicated Alzheimer's disease, and therefore to establish what constitutes significant changes in functioning. Study II and Study III are designed to detail the toxic effects of anticholinergic drugs commonly prescribed to Alzheimer's patients. These studies will serve to assess the validity and clinical applicability of the methods developed in Study I. The outcome of the proposed research will be the development of a clinically applicable method for monitoring AD patients that will aid in the prevention of excess disability.
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