Mechanisms of Cognitive Fluctuations in ADRD Populations (R01 - Clinical Trial Optional)

Funding Opportunity RFA-NS-25-014 from the NIH Guide for Grants and Contracts. "Fluctuating cognition can occur in many types of dementia and is a core clinical feature of Dementia with Lewy Bodies. Cognitive fluctuations can last from seconds to days, are unpredictable (e.g., do not just occur in the evenings, as with sun-downing), and are associated with poor daily functioning for the patient. A number of small studies have suggested that cognitive fluctuations in subjects with dementia may be related to epileptiform discharges and impaired oscillatory activity on EEG, but it is not clear that these are the only factors involved in patient populations that often experience dysautonomia, orthostasis, and sleep disturbances. The etiology of cognitive fluctuations may be multi-factorial and may vary in different dementia populations. Understanding the physiology related to cognitive fluctuations is a critical next step to the development of treatment approaches and improving quality of life for these patients. This initiate would encourage research that will better characterize the physiology responsible for cognitive fluctuations in ADRD populations. Given their variable appearance and time course, it is anticipated that wearable digital devices will be important for capturing fluctuations in a timely fashion, and applicants should consider incorporating those device(s) capable of acquiring the relevant data to support the hypothesized mechanism(s). Applicants may focus on assessing multiple mechanisms in a specific ADRD population, or may chose to compare mechanisms across multiple types of ADRDs. "