This proposed K23 career development award will provide Nancy Kerner, MD, Assistant professor of Psychiatry at Columbia University, with mentored career development to establish an independent research career in the study of the association of poor sleep and disrupted circadian rhythms with mild cognitive impairment (MCI) and dementia. Poor sleep and disrupted circadian rhythms are common in older adults with mild cognitive impairment (MCI) and dementia, including Alzheimer?s disease and related dementias (ADRD), whereas more than half of adults aged 65 years or older have sleep disorders, less than half are diagnosed. Also, there is strong evidence that obstructive sleep apnea (OSA) is highly prevalent in older adults, and some individuals with untreated OSA have rapid cognitive transitions from normal cognition to MCI and from MCI to dementia. However, the associations between poor sleep and disrupted circadian rhythms with clinical cognitive diagnoses have not been studied. The goal of this K23 award is to advance Dr. Kerner?s research career by (a) providing mentored career development and training in patient-oriented research (POR) in sleep and circadian disturbances across all stages and (b) conducting a study to assess sleep and circadian rhythms with the PROMIS sleep questionnaires and actigraphy among the elderly evaluated for ADRD in primary care practices. The proposed project is an ancillary study to an ongoing project of dementia detection among persons 65 years or older with cognitive concerns in primary care, in which the primary mentor Luchsinger and co-mentor Devanand are the principal investigators. The primary aim is to examine cross-sectionally and longitudinally the association of poor sleep and disrupted circadian rhythms with cognitive diagnostic categories based on the NIA-AA criteria, including dementia, amnestic MCI single domain, amnestic MCI multiple domain, and cognitive impairment no MCI. The relation of OSA with diagnostic categories will also be explored. The secondary aim is to examine the relationship of cognitive transitions with new onset of abnormal sleep and disrupted circadian rhythms. The exploratory aim is to explore the interactions of poor sleep and disrupted circadian rhythms with AD risk factors (e.g. APOE genotype) in relation to transitions from normal cognition to MCI and from MCI to dementia.
These research aims will be complemented by training in (1) cognitive testing and diagnosis, (2) sleep and circadian rhythm scoring, (3) circadian metrics analyses, (4) statistical analyses of cross-sectional and longitudinal data, (4) methods to assess temporality of associations, such as path analysis, and (5) mediation and moderation analyses. Collectively, the career development plan, research project, and training activities will build a sound platform for Dr. Kerner to become an independent investigator in sleep/circadian rhythms and ADRD research.
This application is responsive to the 2015 AD Summit recommendation to ?elucidate the short- and long-term consequences of disrupted and optimized sleep on brain aging and AD.? Sleep and circadian rhythm disturbances are common in elderly persons with mild cognitive impairment (MCI) and dementia, including Alzheimer?s disease and related dementias (ADRD). This proposed K23 award will support a research career to examine cross-sectionally and longitudinally the association of poor sleep and disrupted circadian rhythms with cognitive diagnoses, including normal cognition, cognitive impairment without MCI, amnestic MCI single domain, amnestic MCI multiple domain, and ADRD.