2.1. Study Design and Patients

A prospective longitudinal study was designed to examine the effect of sleep quality improvement on neuropsychological behaviors and the changes of blood Aβ_42/40 ratio and Tau-pT181 levels in patients with mild cognitive impairment due to Alzheimer’s disease accompanied with sleep-disordered breathing. Patients were recruited at the Memory and Sleep Clinic at the Jianghan Oilfield General Hospital from February 2017 to December 2019. The diagnosis of AD dementia was made based on the core diagnostic criteria developed by the National Institute on Aging-Alzheimer’s Association in 2011 [25]. The diagnostic criteria for sleep-disordered breathing in AD patients were based on the definition of “Dementia-related sleep disorders” in the International Classification of Sleep Disorders guidelines [26] and the clinical diagnostic criteria for Alzheimer’s disease-related sleep disorders [27]. Other inclusion criteria include no severe dysfunctions or lesions of the heart, lung, liver, kidney, and other vital organs and the ability to complete relevant neuropsychological assessment and auxiliary examination. Exclusion criteria included: (1) severe dementia; (2) other types of cognitive impairment, including vascular dementia, Parkinson’s disease, frontotemporal dementia, Lewy body dementia; (3) a history of severe mental illness; (4) association with a severely debilitating illness, infectious disease, painful condition or other diseases that may affect the quality of sleep, such as chronic obstructive pulmonary disease, stroke, heart failure, kidney failure, severe cerebrovascular disease, epilepsy; and (5) severe physical movement disorder.

The study protocol was reviewed and approved by the Ethics Committee of the Jiangshan Oilfield General Hospital (study ethical code number 2017016, approval date 20170226). All the patients and their immediate family members were informed with a written consent form, and the patient’s signatures were obtained before enrollment. This study was conducted according to the principles stated in the Declaration of Helsinki [28].

After diagnosis and recruitment, all patients were managed by dedicated research nurses responsible for collecting demographic data, medical history, physical examination, behavioral and neuropsychological assessment, biochemical specimen collection, and regular follow-up. Structured questionnaires were used to assess patient medical history, gender, age, onset age of the disease, course of the disease, years of education, marital status, the living situation at home, and patient support level on the enrollment day. Patients were requested to spend one night at the hospital, where peripheral blood specimens were collected in the morning before daytime activity.

The Pittsburgh Sleep Quality Index (PSQI) questionnaire (a Chinese version) was used to evaluate patients’ overall sleep quality [29,30]. There were 18 items on the scale divided into seven sub-items: subjective sleep quality, time to sleep, sleep time, sleep efficiency, night sleep disturbance, sleep drug use, and daytime dysfunction. Each item’s score is 0–3 points, and the total score is 0–21 points. A PSQI score at or above five was set as the cutoff value for a sleep disorder.

The Montreal Cognitive Assessment Scale (MoCA) was used to assess patient cognitive function [31]. There were seven cognitive domains: visuospatial and executive function, naming, delayed recall, attention, language, abstraction, and orientation. A total score of less than 26 was considered as cognitive impairment.

The Clinical Dementia Assessment Scale (CDR) was used to provide a global evaluation of the severity of dementia [32]. A CDR score of 1 was classified as mild, 2 as moderate, and 3 as severe. The Global Deterioration Scale (GDS) was used to assess the extent and progress of dementia [33], which provides an overview of a patient who has degenerative dementia. The GDS scale was divided into seven levels and was completed by interviewing the patients and their caregivers. A GDS score of 1 indicates no cognitive impairment; 2 indicates a very mild cognitive impairment, 3 as mild, 4 as moderate, 5 as severe, 6 as very severe, and 7 as worst impairment.

The 24-item Hamilton Rating Scale for Depression (HRSD-24) was utilized to assess patient depressive symptoms [34]. In the HRSD-24 version, a total score of 8 or less was classified as no depression, 9–20 as suspicious depression, 21–35 as moderate or mild depression, and above 35 as severe depression.

The Hamilton Anxiety Scale (HAMA) was used to evaluate patient anxiety, and there were 14 items on this scale [35]. The scale adopts a 5-point scoring method ranging from 0 to 4 points. A total score less than 7 indicated no anxiety, 7–13 was classified as possible anxiety, 14–20 was anxiety, 21–28 was classified as significant anxiety, above 29 was classified as severe anxiety.