The association between sleep restlessness and neuroimaging biomarkers of Alzheimer’s Disease in mid‐life to older adults and patients

Abstract Background Recent research demonstrates a bidirectional relationship between sleep and Alzheimer’s Disease (AD) pathology, with supporting evidence that changes in sleep pattern occurs from the preclinical stage of AD. The cooccurrence of sleep disturbances and amyloid‐beta (Aβ) accumulation suggests the importance of monitoring sleep patterns in adults that are at high‐risk of developing AD later in life. We first investigated whether resting heart rate (RHR) and nocturnal sleep restlessness (NSR) are different in cognitively impaired (CI) and cognitively unimpaired (CU) mid‐life to older adults. We also examined any association of these sleep characteristics with hippocampus volume (HV) and Aβ, as neuroimaging biomarkers of AD, regardless of the cognitive status. Method 107 middle to old age (46‐75 years old) adults (age 61.5±6.5, 74 Females, 64 APOE ε4 carriers, and 88 CU) underwent 3T MRI and PET scans as part of the Prospective Imaging Study of Ageing (PISA) study. A ballistocardiograph sleep monitoring device was used to track their RHR and NSR for approximately 5 months after their PET scan. NSR was quantified by total time in bed, total duration and number of bed‐exits, and multi‐episodic sleep. HV was normalised using total intracranial volume, and Aβ load was calculated in Centiloid scale (CL) with Aβ positivity defined as CL>20. Generalised Linear Models were used to examine the relationship between sleep and imaging biomarkers. Age, gender, BMI, APOE, and years of education were used as independent covariates. Result CIs spent more time in bed (p = 0.002) and had more bed‐exits (p = 0.009) than CUs. However, no significant difference was found on RHR and multi‐episodic sleep between CUs and CIs. Individuals with higher Aβ load, regardless of their cognitive status, had lower RHR (p = 0.04) and more bed‐exits (p = 0.04), and spent more time in bed (p = 0.01). Also, individuals with smaller HV frequently exited the bed during the night (p = 0.03) and spent more time in bed (p = 0.003). Conclusion Individuals with cognitive impairment experienced higher levels of NSR with frequent bed‐exits and more time in bed. Also, these sleep characteristics were significantly associated with the Centiloid value, Aβ status, and HV, regardless of the cognitive status.