This is a revised competitive renewal investigating how the circadian timing system is altered in dementia. In a previous version of the application, we sought to study this problem by correlating antemortem descriptions of agitated behavior over the 24-hour day with postmortem neuroanatomic findings from regions hypothesized to control those behaviors. In the present study, we will rely on physiologic assessments of the circadian timing system in living geriatric patients with known disease to index integrity and functional status of the circadian timing system. Nocturnal disruptive behavior, sometimes called """"""""sundowning,' represents a major problem in the care of elderly patients. Many, but not all, patients with dementia show dramatic upheaval of their sleep/wake cycle, a condition often characterized as """"""""day/night reversal."""""""" For individuals not yet institutionalized, such agitated behavior at night represents a major cause of nursing home placement and is a severe stressor for family members. Within the nursing home environment, such behaviors cause upheaval among staff and other patients, and often lead to unsuccessful treatment with neuroleptic medications. While some researchers have focused on environmental factors underlying such disruptive behavior, our emphasis has been on neurobiologic causes for such """"""""sundowning."""""""" One possible substrate for such behavior involves the brain region known to control the timing of sleep/wakefulness, rest/activity and the 24-hour periodicity of nearly all physiologic functions, including the diurnal body temperature cycle. This area, an extremely small region called the suprachiasmatic nucleus (SCN) located in the anterior portion of the hypothalamus, is known to undergo marked changes with normal aging. Additionally, there is some evidence to suggest that certain forms of dementia may be associated with even greater deterioration in this region. The proposed study will assess the output of this brain region by examining the 24-hour body temperature cycle and sleep/wakefulness in elderly patients with Alzheimer's Disease (AD), Parkinson's Disease (PD), Vascular Dementia (VasD) and aged matched controls. Individuals will be studied in the sleep laboratory over a period of 3 1/2 days during which they will undergo frequent body temperature measurements and polysomnography on an altered sleep/awake schedule alternately allowing 30 minutes for sleep and 60 minutes of wakefulness. Based on existing behavioral, neuroanatomical and physiological evidence, we expect the greatest disruption of circadian physiology to occur in VasD, the least disruption in controls, and an intermediate level of disruption in AD and PD. These results will provide information on the mechanistic basis for sundowning in aged patients with dementing disorders.
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