Grant: Fellowship: Bisby (Prize)

Older people, particularly those with dementia, commonly have sleep problems - especially difficulty falling and staying asleep. However, despite the clinical significance of these problems, we still do not completely understand their biological basis. Recent animal experiements have identified a group of brain cells called the ventrolateral preoptic nucleus (VLPO) as being critial to sustained sleep. Damage to the VLPO in animals leads to a fragmented pattern of sleep similar to that seen in many older people. Moreover, preliminalry evidence suggests that the human equivalent of the VLPO degenerates with age. We think that age-related dgeneration in the human VLPO may be the basis of many sleep problems in older people. To test this, we will study individuals participating in the Religious Orders Study - a Chicago-based study involving older priests, nuns, or monks, all initially cognitively normal, who have agreed to annual physical and cognitive assessments and brain donation after death. This study has enrolled over 1000 participants since 1993. Approximatley 3/4 of these participants have had their sleep-wake cycles measured using special wrist-worn devices called actigraphs. We will study the donated brains of participants who had undergone actigraphy before death. We will identify VLPO in these brains, and quantify the degree of degeneration. We will see how age influences the integrity of the VLPO. We will also see how degeneration in the VLPO correlates with the quality of sleep before death. We believe that we will confirm that the VLPO degenerates with age, and that the amount of degeneration will correlate with the degree of sleep fragmenetation. If this is true, this study will be the first to show that degeneration in the VLPO impairs human sleep. In so doing, it will provide insight into the cause of poor sleep in elderly non-demented and demented people, and open the door to the development and testing of therapies for the same.