RF1AG080609

EFFECTS OF SUCCESSFUL OSA TREATMENT ON MEMORY AND AD BIOMARKERS IN OLDER ADULTS (ESSENTIAL) - THE PREVALENCE OF ALZHEIMER DISEASE (AD) IS HIGH AND PROJECTED TO INCREASE. FURTHER, EPIDEMIOLOGICAL DATA SUGGESTS THAT ~15% OF AD RISK MAY BE ATTRIBUTED TO SLEEP PROBLEMS. OBSTRUCTIVE SLEEP APNEA (OSA) IS ALSO COMMON AMONG THE ELDERLY (30-55%), AND OUR PRIOR WORK HAS ESTABLISHED THAT COGNITIVELY NORMAL OLDER WOMEN WITH OSA HAVE NEARLY DOUBLE THE 5-YEAR RISK OF DEVELOPING MILD COGNITIVE IMPAIRMENT (MCI) OR DEMENTIA. FURTHER, WE SHOWED THAT: I. OSA PATIENTS TREATED WITH POSITIVE AIRWAY PRESSURE (PAP) EXPERIENCED SIGNIFICANT OVERNIGHT INCREASES IN PLASMA NEUROFILAMENT LIGHT (NFL), A MARKER OF NEURAL INJURY, WITH STRONG TRENDS FOR AD- SPECIFIC BIOMARKERS (I.E. AΒ40 AND TAU) AFTER PAP WITHDRAWAL; II. OSA PREDICTED LONGITUDINAL INCREASES IN AD BIOMARKERS; AND, III. PAP TREATMENT DELAYED THE ONSET OF MCI IN SUBJECTS WITH REPORTED OSA. THERE IS THEREFORE STRONG EVIDENCE SUGGESTING THAT OSA TREATMENT COULD BE AN IMPORTANT PREVENTION STRATEGY FOR AD. HOWEVER, TRIALS FOR TREATMENT OF OSA TO SLOW COGNITIVE DECLINE AND PROGRESSION TO AD FACE A NUMBER OF CHALLENGES. FIRST, THE MOST EFFECTIVE THERAPY (PAP) HAS POOR ADHERENCE. A SECOND CHALLENGE IS DEFINING THE TARGET POPULATION: PRIOR TRIALS TARGETED OSA PATIENTS WITH MCI/AD, WHO HAVE MORE ADVANCED DISEASE AND COULD BE LESS AMENABLE TO TREATMENT. A THIRD CHALLENGE IS IDENTIFYING COGNITIVE TESTING THAT IS SENSITIVE TO SLEEP DISRUPTION, AND LINKED TO INCREASED AD RISK. (TO CAPTURE EFFECTS OF OSA ON THE OFFLINE PROCESSING PHASE REQUIRES SLEEP-DEPENDENT MEMORY PARADIGMS, IN WHICH THE ENCODING AND RECALL OF INFORMATION ARE SEPARATED BY A PERIOD OF SLEEP WITH/WITHOUT OSA). FINALLY, A RANDOMIZED TRIAL OF SUFFICIENT DURATION TO TEST THE EFFECTS OF TREATMENT OF OSA ON RISK OF INCIDENT AD IS NOT FEASIBLE. OUR PROPOSED TRIAL, EFFECTS OF SUCCESSFUL OSA TREATMENT ON MEMORY AND AD BIOMARKERS IN OLDER ADULTS (ESSENTIAL), ADDRESSES THESE CHALLENGES. ESSENTIAL IS A 5-YEAR STUDY OF COGNITIVELY NORMAL OLDER ADULTS WITH NEWLY DIAGNOSED OSA, AGES 55-75, RECRUITED FROM 4 WELL-ESTABLISHED SLEEP CLINICS. OSA PATIENTS (N=200) WILL BE RANDOMIZED TO EITHER: I) A 3-MONTH OSA TREATMENT BY ANY COMBINATION OF PAP, OAT, AND POSITIONAL THERAPY THAT RESULTS IN AN “EFFECTIVE” IMPROVEMENT IN THE APNEA-HYPOPNEA INDEX (AHI); II) A WAITLIST CONTROL GROUP TO RECEIVE TREATMENT AT THE CONCLUSION OF THE 3-MONTH INTERVENTION PERIOD. EFFECTIVELY TREATED INDIVIDUALS (~150) AND UNTREATED INDIVIDUALS (~100) WILL THEN BE FOLLOWED FOR UP TO 24 MONTHS TO COMPARE WHETHER SUSTAINED IMPROVEMENTS IN AHI ARE ASSOCIATED WITH BETTER COGNITIVE FUNCTION AND AD BIOMARKER CHANGE PROFILES AS COMPARED TO UNTREATED CONTROLS. PARTICIPANTS WILL UNDERGO PSG, ACTIGRAPHY, COGNITIVE TESTS, AND BLOOD DRAWS AT BASELINE, 3 AND 24 MONTHS. OUR AIMS ARE: 1) TO COMPARE 3-MONTH CHANGE IN PLASMA AD BIOMARKERS (NFL, P-TAU, AΒ) BETWEEN THOSE RANDOMIZED TO OSA TREATMENT AND WAIT-LIST CONTROL GROUPS; 2) TO COMPARE 3-MONTH CHANGE IN COGNITION BETWEEN THE OSA TREATMENT AND WAIT-LIST CONTROL GROUPS; 3) TO EXAMINE IF SUSTAINED REDUCTION IN AHI OVER 24 MONTHS AMONG EFFECTIVELY TREATED PARTICIPANTS VERSUS UNTREATED CONTROLS IS ASSOCIATED WITH BETTER 24-MONTH CHANGE PROFILES FOR AD BIOMARKERS AND COGNITION.

Sutter Bay Hospitals

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

San Francisco, California 941075419 United States

Single Zip Code

Early and Late Stage Clinical Trials for the Spectrum of Alzheimers Disease/Alzheimers Related Dementias and Age-Related Cognitive Decline (R01 Clinical Trial Optional) (PAR-21-359)