Sleep Disorders

Circadian and Sleep

Circadian and Sleep Phenotypes and Cognitive Impairment in Alzheimer's Dementia (N = 53)

2015 – 2019

CL = cognitively normal APOEƐ4 non-carriers, HR = cognitively normal at high risk for AD, MCI-AD = mild cognitive impairment with positive AD biomarkers

Three groups were examined: (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). The center evaluated actigraphy-based (Motionlogger® Micro Watch, 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) and recording time < 90% SaO2 across the groups and assessed association with cognition (Mini-Mental State Exam (MMSE)). 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 (coefficient 0.49, 95% CI [0.03, 0.95], P = 0.038), 1 hour increase in TST was associated with 0.81 point higher MMSE (coefficient 0.81, 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 < 90%, MCI-AD had the largest and HR the lowest SFI, and MCI-AD had lesser robustness but higher mesor and amplitude. In this comparative analysis of 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.