This federal Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) totaling $258,498 will support research to investigate the biological pathways linking sleep health to Alzheimer's disease and cognitive decline. The 5-year project, awarded to the University of California, Los Angeles (UCLA), aims to utilize a multi-omics approach to analyze methylation and metabolomics data associated with short sleep and insomnia, and compare these results to known Alzheimer's...
This $191,700 Project Grant awarded by the National Institute on Aging (CFDA 93.866 - Aging Research) to Northwestern University will support the "SLEEP HEALTH AND COGNITIVE FUNCTION AMONG MIDDLE-AGED ADULTS: THE SLEEPCOG STUDY". The key objectives are to: 1) investigate the associations between sleep disturbance, cognitive function, self-care capacity, and health status among middle-aged adults; 2) develop sleep disturbance prediction models from electronic health record data; and...
This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) provides $446,875 to The Trustees of the University of Pennsylvania to investigate the potential pleotropic effects of Alzheimer's disease genetic risk variants on sleep. The researchers will leverage variant-to-gene mapping and zebrafish models to determine if genes associated with Alzheimer's disease risk also impact sleep duration and other sleep phenotypes. The award period runs from January 1,...
This $1,955,041 Project Grant from the National Institutes of Health's National Institute on Aging, under the Aging Research program (CFDA 93.866), will fund research into the relationship between sleep, pericytes, and Alzheimer's disease pathology. The Medical University of South Carolina will investigate whether pericytes, cells that regulate cerebral blood flow and blood-brain barrier permeability, mediate the effects of sleep disruption on Alzheimer's disease progression. Specifically, the...
The National Institute on Aging (NIA) awarded a $131,085 Project Grant under the Aging Research federal grant program (CFDA 93.866) to The Leland Stanford Junior University (Stanford University) to investigate the utility of afternoon phototherapy as a stepped care approach to reduce sleep-wake fragmentation and improve cognition in older adults with mild cognitive impairment. The key objectives of this 2-year project are to: 1) apply state-of-the-art machine learning techniques to identify...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $406,217 to the University of Texas Health Science Center at Houston (UTHealth) to investigate the role of circadian regulation and the adenosine kinase (ADK) enzyme in cognitive dysfunction following cranial radiotherapy (CRT) for brain cancers. The key objectives are to determine how CRT disrupts the BMAL1-mediated regulation of ADK in astrocytes, leading to sleep-wake cycle...
This federal Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) for $624,000.00 will support research to explore prioritizing patient care preferences for older women with breast cancer and multiple chronic conditions. The project aims to develop and pilot test a "Patient Priorities Care" framework to facilitate individualized survivorship care for this population. This will involve two key components: (1) a session with patients to identify their...
The National Institute on Aging (NIA) awarded Brigham & Women's Hospital Inc. a $2,576,936 Project Grant under the Aging Research federal grant program (CFDA 93.866) to characterize the variability in sleep spindle activity across a population and evaluate the use of sleep spindle dynamics as biomarkers for Alzheimer's disease, mild cognitive impairment, and trisomy 21. The 3-year project will develop statistical models and methods to analyze sleep spindle patterns and their relationship...
This Project Grant from the National Institute on Aging, part of the Department of Health and Human Services, will fund research into the molecular interplay of sleep and neurodegeneration using the Drosophila model system. With $2.14 million provided over 11 months, the Trustees of the University of Pennsylvania will investigate how expression of the TDP-43 protein linked to neurodegenerative diseases disrupts sleep in fruit flies. Researchers will aim to define the specific glial subtypes...
This federal Project Grant award of $828,960 from the National Institute on Aging (CFDA 93.866 - Aging Research) to Cedars-Sinai Medical Center supports research to examine the role of biological aging mechanisms in Alzheimer's disease and related dementias (ADRD). The key objectives are to: Evaluate how aging pathways and hallmarks (e.g., cellular senescence, mitochondrial dysfunction, inflammation) are linked to ADRD biomarkers, and how their trajectories relate to changes in cognition and...
PATTERNS OF BIOLOGICAL, COGNITIVE, AND PHYSICAL AGING IN CANCER SURVIVORS AND CONTROLS AND THE ROLE OF SLEEP HEALTH: RELEVANCE FOR ALZHEIMER'S DISEASE AND RELATED DEMENTIAS - ABSTRACT WE USE A GEROSCIENCE FRAMEWORK TO ADVANCE ALZHEIMER'S DISEASE-RELATED DEMENTIAS (ADRD) RESEARCH BY ESTABLISHING HOW BIOLOGICAL AGING AFFECTS COGNITIVE AND PHYSICAL DECLINE AND DEFINING THE ROLE OF SLEEP IN THESE RELATIONSHIPS. WE USE THE INTERFACE OF AGING AND BREAST CANCER IN OLDER WOMEN FOR THIS PURPOSE BECAUSE OF THEIR UNIQUE BI-DIRECTIONAL RELATIONSHIPS. BIOLOGICAL AGING PROCESSES INCREASE THE RISK OF DEVELOPING CANCER, SO THAT NEWLY DIAGNOSED BREAST CANCER PATIENTS MAY HAVE ACCELERATED AGING PRIOR TO THERAPY. CANCER TREATMENTS CAN FURTHER ACCELERATE AGING PROCESSES. DESPITE POSSIBLE INVERSE RELATIONSHIPS BETWEEN CANCER AND ADRD, BREAST CANCER THERAPY IS ASSOCIATED WITH SHORT-TERM COGNITIVE DECLINE AND THIS MAY BE DUE TO THE EFFECTS OF ACCELERATED BIOLOGICAL AGING ON UNDERLYING EARLY ADRD OR DAMAGE TO SIMILAR SYSTEMS AS INVOLVED IN ADRD. AS WE AGE, SLEEP IS FUNDAMENTAL TO REPAIRING DAMAGE TO MAINTAIN SYSTEM REGULATION AND HOMEOSTASIS, INCLUDING CLEARANCE OF WASTE PRODUCTS SEEN IN ALZHEIMER'S DISEASE (AD). POOR SLEEP IS COMMON IN CANCER SURVIVORS AND SLEEP HAS BEEN ASSOCIATED WITH BIOLOGICAL AGING AND/OR PHYSICAL DECLINE AND COGNITIVE PROBLEMS AND INCREASED RISK FOR ADRD IN NON-CANCER SETTINGS. HOWEVER, THERE IS VERY LIMITED LONGITUDINAL RESEARCH TESTING THESE RELATIONSHIPS IN OLDER SURVIVORS WITH CONTROL GROUPS TO INFORM RESEARCH INTO COGNITIVE AGING AND EARLY ADRD. OUR TRANSDISCIPLINARY TEAM OF NATIONALLY RECOGNIZED LEADERS IN AGING AND CANCER, BIOLOGICAL AGING, SLEEP, NEUROSCIENCE, ALZHEIMER'S DISEASE AND GERIATRICS ARE UNIQUELY PLACED TO FILL THIS GAP. THE PROPOSED STUDY LEVERAGES AN EXTANT COHORT TO EFFICIENTLY CONDUCT A NOVEL NEW STUDY OF THE EFFECTS OF BIOLOGICAL AGING ON HEALTH. OUR PRIMARY RESEARCH QUESTIONS ARE: 1) DO BREAST CANCER SURVIVORS HAVE MORE BIOLOGICAL AGING BEFORE SYSTEMIC TREATMENT THAN CONCURRENT FREQUENCY- MATCHED NON-CANCER CONTROLS?, 2) DO SYSTEMIC TREATMENTS DRIVE FURTHER BIOLOGICAL AGING AND LOWER COGNITIVE AND PHYSICAL FUNCTION IN SURVIVORS BEYOND THAT SEEN IN NON-CANCER CONTROLS OVER TIME? AND 3) DOES POOR SLEEP LEAD TO MORE AGING AND LOWER FUNCTION? TO ADDRESS THESE QUESTIONS, WE BEGIN WITH BREAST CANCER SURVIVORS (N=368) AGED 60+ AND CONTEMPORANEOUSLY EVALUATED NON-CANCER CONTROLS (N=354) FREQUENCY-MATCHED TO SURVIVORS ON AGE, RACIAL GROUP, EDUCATION LEVEL AND RECRUITMENT SITE. THESE WOMEN HAVE RICH PRE-TREATMENT/ENROLLMENT NEUROCOGNITIVE, PHYSICAL AND SLEEP DATA AND BLOOD OBTAINED AND BANKED TO SPECIFICALLY TEST AGING MARKERS. WE WILL CONDUCT FOLLOW-UP OUT TO 48-MONTHS AND PERFORM ASSAYS OF SEVERAL HALLMARKS OF BIOLOGICAL AGING (EPIGENETIC AGE, DNA DAMAGE, CELLULAR SENESCENCE, SASP, AND LEUKOCYTE TELOMERE LENGTH). WHILE ACCELERATED BIOLOGICAL AGING HAS BEEN POSTULATED TO EXPLAIN COGNITIVE AND FUNCTIONAL DECLINE AMONG PEOPLE WITH AND WITHOUT CANCER, THIS RIGOROUS PROJECT WILL BE THE FIRST TO OUR KNOWLEDGE TO DEFINITIVELY EVALUATE THIS THEORY. THE POPULATION AND QUESTIONS PROPOSED ARE SIGNIFICANT AND WILL ONLY BECOME MORE IMPORTANT WITH THE AGING OF THE POPULATION. THIS CLINICAL TRANSLATIONAL PROJECT ADDRESSES KEY NIA PRIORITY AREAS AND WILL PROVIDE IMPORTANT DATA TO INFORM FUTURE ADRD STUDIES AND INTERVENTIONS TO IMPROVE HEALTH AND RESILIENCE OF OUR AGING POPULATION.