Studies of sleep-wake regulation in normal and pathologic aging continue to hold considerable experimental interest and clinical relevance for psychiatry. Investigations of nocturnal EEG sleep in healthy elderly controls, major depressives, and probable Alzheimer dementia patients will now be extended to patients with mixed symptoms of depression and dementia, some of whom will have reversible dementia of depression, and others of whom will have early Alzheimer's dementia with depression. The clinical goal remains the development of objective indicators of diagnosis, treatment response to antidepressant therapy, and prognosis. This goal will be achieved by comparing baseline sleep measures among groups of mixed-symptom patients who are responders, partial responders, or non-responders to adequate antidepressant therapy. Furthermore, patients and controls will be followed for two years to ascertain the presence or absence of dementia of the Alzheimer type. Baseline sleep, clinical, socio-demographic, and treatment response variables will be entered into a discriminant function to determine how well they predict presence/absence of dementia at two years. The discriminant function will be cross-validated in a second group of patients. The experimental hypothesis is that patients with reversible dementia of depression will show sleep and other psychobiologic measures similar to those of depressives without cognitive impairment, while other mixed-symptom patients with early Alzheimer's disease and symptoms of depression will show sleep and psychobiologic measures more similar to those of Alzheimer patients studied to date. This hypothesis will be tested both under unchallenged conditions and with either naturalistic or pharmacologic probes: limited total sleep deprivation, REM sleep deprivation, and measurement of arecoline REM-induction responsivity. We expect that reversible dementia of depression will be distinguishable from Alzheimer's dementia with depression by 1) greater REM and slow wave sleep rebound in the first third of the recovery night; and 2) by more rapid arecoline induction of REM sleep. Sleep studies will be integrated with 24-hour studies of core body temperature rhythm and psychomotor activity in healthy elderly controls in a further examination of the developmental aspects of sleep abnormalities in depression.
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