Alterations In Macro And Micro Sleep Architecture And Their Relationship With Cognitive Changes In Patients With Alzheimer’s Disease

Alzheimer’s disease(AD),a neurodegenerative disease that is common in old age and is characterized by progressive memory loss and overall cognitive decline.It is one of the largest global public health challenges of the 21 st century.However,there is no effective treatment for AD so far,so early identification of people at risk of AD and early intervention may be one of the effective ways to prevent AD.The sampling of existing AD biomarkers is mostly invasive and expensive.Therefore,exploring new,reliable and non-invasive AD biomarkers has important clinical value.In recent years,accumulating studies have shown that there is a bidirectional relationship between AD pathology and sleep,and some characteristics of sleep have the potential to be biomarkers of AD.Most previous studies have focused on sleep macro architecture,but have rarely targeted the changes of micro sleep characteristics.In this study,the changes of macro and micro sleep architecture in patients with AD,as well as the effects of sleep changes on their cognition were investigated.In study 1,polysomnography was used to monitor and record the sleep of AD patients and normal control subjects for a whole night,and compare their differences in the macro sleep architecture.The result of the study showed that the total sleep time and sleep efficiency of AD patients decreased significantly compared with normal control subjects.In addition,in terms of the duration and proportion of sleep stages,the N2 stage duration of non-rapid eye movement sleep,the duration and proportion of rapid eye movement sleep in AD patients were significantly lower than those normal control subjects.In contrast,patients with AD showed a significant increase in the proportion of sleep stage N1 and wakefulness time after sleep compared with normal control subjects.The results of macro sleep architecture suggested that the proportion of deep sleep and rapid eye movement sleep decreased,while the proportion of light sleep increased,and AD patients had greater difficulty in sleep maintenance,presenting with longer wake time after sleep.Study 2 focused on the sleep spindles(11-15 Hz)related to memory consolidation to investigate the changes in the micro sleep characteristics in patients with AD.The results showed that spindle density,amplitude,and duration decreased significantly in patients with AD compared to normal control subjects.When sleep spindles were divided into fast(13-15 Hz)and slow(11-13 Hz)spindles by frequency,the results of the two kinds of spindles were similar in terms of spindle density,amplitude and duration,which showed a decrease with AD pathology.In addition,fast spindle frequency in AD patients was significantly higher than normal control subjects.The results of micro sleep architecture suggest that sleep spindle of AD patients is significantly affected by the disease,which is characterized by decreased spindle density,amplitude and duration,and increased spindle frequency.Study 3 explored the relationship between macro and micro sleep characteristics and their cognition in patients with AD,and further explored the biomarkers of AD from the perspective of sleep indicators.The results showed that there was no significant correlation between the macro sleep architecture of AD patients and their cognitive ability.However,in terms of micro sleep architecture,slow spindle frequency and fast spindle density were negatively correlated with the overall cognitive ability of AD patients,which showed that the cognitive ability of AD patients decreased with the.In addition,binary logistic regression analysis showed that wake time after sleep can be used to as a potential biomarker to distinguish between normal control and AD patients,suggesting that increased wake time after sleep may be the causes of cognitive impairment in AD patients.Taken together,this study explored the macro and micro changes in sleep characteristics of patients with AD and the relationship between them and their cognitive changes.The results showed that patients with AD showed symptomatic changes in sleep architecture and sleep spindle,and the changes of these sleep indicators were significantly correlated with the decline of comprehensive cognitive ability.At the same time,the wake time after sleep could be used as a sleep biomarker to distinguish AD from normal control subjects.This thesis provides evidence from sleep for the early identification and diagnosis of AD.Future studies can reveal the relationship between specific sleep changes and AD,and carry out targeted intervention to find a new breakthrough for the prevention and treatment of AD.