Characteristics Of Sleep Disorders In Patients With Alzheimer's Disease And Their Relationship With TCM Syndrome

Objective:To study the relationship between sleep disorders,TCM syndromes and cognitive function in patients with Alzheimer’s disease(AD),and to provide evidence for the treatment of Alzheimer’s disease from the perspective of sleep disorders.Methods:A total of 381 elderly patients,aged 70.66 ± 10.08 years old,were enrolled in the outpatient and inpatient departments of Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2019 to February 2023,including 246 cognitively normal patients and 135 AD patients.According to the Pittsburgh Sleep Index,a total score of>7.5 indicates the presence of sleep disorders in 158 cognitively normal patients and 80 in the Alzheimer’s disease group.A cross-sectional survey was conducted on all subjects by means of scale assessment and polysomnia monitoring,including the Pittsburgh sleep quality index(PSQI).Epworth sleepiness scale(ESS);Sleep disorder iventory(SDI);Polysomnography(PSG);Neuropsychological assessment:Mini-mental state examination(MMSE),Immediate story recall(ISR),Delayed story recall(DSR),Clock drawing test(CDT),Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD),Neuropsychiatric inventory(NPI)was investigated,and The pattern element scale-11 items(PES-D-11)were used for TCM syndromes of dementia.Statistical analysis was performed using SPSS25.0.T-test or Wilcoxon signed rank sum test were used for comparison between groups.Chi-square test and non-parametric test were used to compare the distribution characteristics of sleep and syndrome among groups.Spearman correlation analysis was used to analyze the correlation between sleep scale scores of AD patients with sleep disorders and TCM syndrome,and Spearman correlation analysis was used to detect the correlation between sleep structure and neuropsychological scale scores of AD patients.The risk factors affecting sleep in patients with AD were analyzed by binary Logistic regression.Results:1.135 cases(35.4%)in AD group and 246 cases(64.6%)in Normal cognition(NC)group.The average age of AD group(74.31 ± 9.73 years)was significantly higher than that of NC group(70.66±10.08 years)(P=0.000),and the time of education of AD group(10.09±4.83 years)was significantly lower than that of NC group(12.16 ± 3.11 years)(P=0.007).The prevalence of hypertension(P=0.001),diabetes(P=0.002)and chronic pain(P=0.002)in AD group was significantly higher than that in NC group.In terms of sleep,the incidence of dreaminess in AD group was higher than that in NC group(P=0.006).There was no significant difference in other demographic data(gender,past history,sleep complaints)between the two groups.2.The incidence of sleep disorders(PSQI>7.5)in AD group(59.3%)was lower than that in NC group(64.2%),and there was no statistical difference in PSQI total score(p=0.671).In PSQI sub-item,the scores of sleep quality(P=0.004),sleep disorders(P=0.000)and hypnotic drugs(P=0.000)in NC group were higher than those in AD group,and the scores of sleep efficiency(P=0.010)and daytime dysfunction(P=0.000)in NC group were lower than those in AD group.There was no statistical difference in ESS total score(P=0.175).In ESS sub-item,the scores of taking transportation(P=0.004)and watching TV(P=0.022)in NC group were higher than those in AD group.The low incidence of sleep disorders in AD group may be related to patients’ inability to accurately complete the sleep self-rating scale.3.Binary Logistic regression analysis was performed on AD patients with or without sleep disorders,and the results showed that:for AD patients,the risk of sleep disorders increased by 4.8%for each year of age increase,and the risk of sleep disorders in widowed patients was 3.6 times that of non-widowed patients;For every 1-point decrease in DSR,the risk of sleep disorders increased by 8.3%.The risk of sleep disturbance in stroke patients was 0.34 times higher than that in non-stroke patients.The risk of sleep disturbance in GERD patients was 6.1 times that of non-GERD patients.4.Characteristics of sleep disorders in AD patients:AD patients tend to have difficulty falling asleep,easy to wake up,early wake up,and snoring during sleep.The results of polysomnography monitoring data showed that in terms of sleep structure,the Rapid eye movement(REM)time of AD patients was shorter than that of NC group(P=0.007),and the proportion of REM in AD group was significantly reduced compared with NC group(P=0.004).There was no strong correlation between the respective variables.Only R phase(r=0.444**)and R phase proportion(r=0.418**)were moderately correlated with MMSE-delayed recall.5.The frequency of each syndrome in AD group is as follows from high to low:Kidney(62.2%)(6.7%),blood deficiency,blood stasis(51.1%),pulp decreased(45.9%),deficiency(37.1%),phlegm turbidity(35.6%),followed by(31.1%),hand(29.6%),Yin deficiency(29.6%),Yang deficiency(16.3%),poison(2%).There were statistical differences in the distribution of kidney deficiency(P=0.047),pulp depletion(P=0.042),hyperactivity of Yang(P=0.002)and excessive toxicity(P=0.006).The distribution rates of kidney deficiency(P=0.047)and Yang hyperactivity(P=0.002)in AD group were lower than those in NC group,and the distribution rates of medullary deficiency(P=0.042)and toxic excess(P=0.006)were significantly higher than those in NC group.AD patients were divided into AD with sleep disorder group and AD without sleep disorder group,and the blood deficiency syndrome of AD with sleep disorder group was higher than that of AD without sleep disorder group(P=0.004).AD group associated with sleep disorders of the kidney(62.5%/61.8%),followed by qi deficiency(31.3%/30.9%),(41.3%/30.9%),blood deficiency(61.3%/36.4%),Yin deficiency(35%/21.8%),Yang deficiency(17.5%/14.5%),hand(31.3%/27.3%),and blood The frequency of blood stasis(8.8%/3.6%)was significantly higher than that of AD group without sleep disorder,indicating that the sleep disorder group was more prone to kidney deficiency,spleen deficiency,qi deficiency,blood deficiency and Yin deficiency.Conclusion:AD patients are characterized by poor sleep quality,difficulty falling asleep,shortened sleep time and reduced sleep efficiency.Possible risk factors for sleep disorders in AD patients include hypertension,anxiety,gastroesophageal reflux,and loss of spouse.The sleep structure of AD patients is mainly rapid eye movement period shortened,rapid eye movement period proportion decreased,and REM sleep is related to memory decline of patients.The TCM syndromes of AD patients are mainly kidney deficiency,blood stasis,blood deficiency and marrow reduction.The syndrome of kidney deficiency,decreased pulp,hyperactivity of Yang and excessive toxicity are more common in AD patients.The traditional Chinese medicine syndromes of AD patients with sleep disorder are mainly kidney deficiency,blood deficiency,qi deficiency and marrow reduction.The higher the score of blood deficiency and Yang deficiency syndrome,the worse the sleep quality.The higher the score of Qi deficiency,phlegm turbidness and blood stasis syndrome,the more serious the daytime dysfunction.