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.
