1009 Association of Circadian Rhythm with 27-Hydroxycholesterol in Amnestic Mild Cognitive Impairment (aMCI) Patients

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Abstract Introduction The 27-hydroxycholesterol(27-OH) has been proposed as a factor mediating the risk of Alzheimer's disease(AD) through oxidative cholesterol metabolism associated with cognitive impairment. Meanwhile, circadian disturbance has been implicated in accelerated aging and incident dementia, mediating metabolic dysregulation, which may lead to neurodegenerative diseases like AD. However, the relationship between circadian rhythm and cholesterol metabolism in MCI is poorly understood. We aimed to compare circadian parameters between amnestic MCI(aMCI) patients and normal controls(NC), and to examine whether changes in circadian parameters can be related with 27-OH levels. Methods Participants over 50 years were recruited from the Memory Clinic at Kangwon National University Hospital, and two public Dementia Care Centers. The diagnosis of aMCI was made according to Petersen’s criteria. Actigraphy monitoring was conducted at home for five days. Nonparametric variables including the inter-daily stability(IS), intra-daily variability(IV) and relative amplitude(RA) were calculated for rest-activity rhythm(RAR) and light exposure rhythm(LER), respectively. DLMO was determined from five hourly saliva samples obtained before sleep onset. The 27-OH levels were measured using high performance liquid chromatography/mass spectrometry(HPLC/MS). Eighteen aMCI patients(76.6 ±6.1 years) and 21 NCs(70.4±6.7years) were finally analyzed. Generalized linear models(GLMs) were used to assess the main effects of circadian parameters on 27-OH levels and their interactions with group. Results There were no significant differences in the RAR and LER variables(IV, IS and RA), and the DLMO between the aMCI and NC groups. In GLMs, significant main effects of RA in RAR and IV in LER on 27-OH levels were shown (β = -461.43, p=.036; β = -149.35, p=.001, respectively). There was no difference in the effects of circadian parameters on 27-OH levels between the aMCI and NC groups (p>.05). Conclusion In our study, a strong 24-hour activity rhythm was associated with lower 27-OH levels, indicating less cholesterol metabolic dysfunction. It suggests that changes in circadian rhythm may affect cholesterol metabolism in preclinical AD patients. Support (if any) Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science and ICT(2020R1F1A1050416);Learning & Academic research institution for Master’s·PhD students, and Postdocs(LAMP) Program of the National Research Foundation of Korea(NRF) grant funded by the Ministry of Education(No. RS-2023-00285353).

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