421 Elucidating Circadian and Sleep Phenotypes and Relation to Cognitive Impairment in Alzheimer’s Dementia

Introduction Although sleep disruption in Alzheimer’s disease (AD) pathogenesis has been described, the role of circadian rhythm dysfunction (CRD) is less understood. We hypothesize greater CRD and sleep disruption with poorer cognitive function in AD compared to normal cognition. Methods We examined 3 groups:1)mild cognitive impairment with positive AD biomarkers(MCI-AD),n=18, 2)cognitively normal at high risk for AD(HR)(APOEƐ4 carriers),n=19, 3)cognitively normal APOEƐ4 non-carriers(CL),n=16 (National Institute of Aging, IMMUNE-AD). DNA extraction and APOEƐ4 genotyping were performed under the Cleveland Clinic Lou Ruvo Center for Brain Health Aging and Neurodegenerative Disease Biobank. We evaluated actigraphy-based (Motionlogger MicroWatch, Ambulatory Monitoring,Inc®) sleep (wake episodes(WE), total sleep time(TST), sleep efficiency(SE), sleep fragmentation index(SFI)) and circadian (mesor, amplitude, robustness, sleep regulatory index(SRI), intradaily stability) predictors and sleep study-based (ApneaLink Air by ResMed®) predictors (apnea hypopnea index(AHI,3% desaturation) and recording time Results Age differed across MCI-AD, HR, and CL groups (68.4±6.2,71.2±3.7,73.7±3.7 respectively,p=0.008). MCI-AD had more WE than HR and CL (14.4±5.6,10.9±3.9,10.9±3.5 respectively,p=0.033). In MCI-AD, the following associations were observed: 5% increase in SE was associated with 0.49 point higher MMSE (coefficient0.49, 95%CI[0.03,0.95],p=0.038), 1 hour increase in TST was associated with 0.81 point higher MMSE (coefficient0.81, 95%CI[0.24,1.37],p=0.006), and 1 unit increase in SFI was associated with 0.36 point lower MMSE (coefficient-0.36, 95%CI[-0.64,-0.08],p=0.013). Key measures differed: CLs had lower AHI, MCI-AD had less TST SaO2 Conclusion In this comparative study of carefully AD biomarker-phenotyped and APOEƐ4-genotyped patients and normal cognition controls, less sleep time and more fragmented sleep are associated with poorer MMSE scores in MCI-AD. Preliminary results show cognitively normal participants at risk of AD(HR) do not show CRD seen in MCI-AD and are more consistent with controls (CL). Support (if any) Catalyst Award. MCI cohort: Alzheimer’s Association, 2014-NIRG-305310. IMMUNE-AD, R01AG022304. CADRC, P30 AG062428. Jane and Lee Seidman Fund.