Correlation of sleep disorders with serum Aβ 1-42 and P-Tau 181 in patients with Alzheimer's disease / 中华老年医学杂志

ABSTRACT

Objective:To investigate the correlation of sleep disorders(SD)with serum levels of amyloid β-proteins(Aβ 1-42)and tau phosphorylated at threonine(P-Tau 181)in patients with Alzheimer's disease(AD). Methods:A total of 126 patients with mild and moderate AD who met the inclusion criteria in the memory clinic, sleep clinic and geriatrics department of Jianghan Oilfield General Hospital affiliated to Yangtze University from February 2017 to January 2020 were included.The Pittsburgh Sleep Quality Index(PSQI)was used to evaluate sleep quality.Patients with PSQI scores ≥7 were included in the AD group with sleep disorders(AD-SD group), and patients with PSQI scores <7 were included in the AD group without sleep disorders(AD-NSD group). The Montreal Cognitive Assessment(MoCA), Global Deterioration Scale(GDS), Clinical Dementia Rating(CDR), Hamilton Rating Scale for Depression(HRSD)and Hamilton Anxiety Rating Scale(HAM-A)were used to evaluate cognitive and psychosocial symptoms.During the same time, biological markers such as serum Aβ 1-42, Aβ 1-40 and P-Tau 181 were detected by using enzyme-linked immunosorbent assays.Patients in the two groups received donepezil as an anti-dementia therapy, while the AD-SD group was treated additionally with a targeted sleep intervention.All patients underwent neuropsychological assessment and biochemical tests at enrollment and at the end of the 6th month, and results from all parameters at baseline and at the end of the 6th month were compared.At the end of the six-month treatment, patients in the AD-SD group were further divided into the recovery AD-SD sub-group and the no-recovery AD-SD sub-group based on the extent of sleep improvement. Results:Of the 126 AD patients, 93(73.8%)had sleep disorders.There was no statistically significant difference between the two groups in gender, age, onset age, educational level, course of disease, CDR, GDS, MoCA, Aβ 1-40 or Aβ 1-42/Aβ 1-40(all P>0.05). The scores of PSQI, HRSD and HAM-A and serum levels of Aβ 1-42 and p-Tau 181 showed statistically significant differences between the AD-ND and AD-NSD groups( P<0.05 or P<0.01). At the end of the 6th month, the scores of PSQI, GDS, HRSD and HAM-A and levels of Aβ 1-42, Aβ 1-40, and P-Tau 181 also showed statistically significant differences between the AD-ND and AD-NSD groups( P<0.05 or P<0.01). There was no statistically significant difference in results from other parameters( P>0.05). Spearman correlation analysis showed that PSQI was correlated with HRSD( r=0.271, P=0.009), HAM-A( r=0.479, P=0.000), Aβ 1-42( r=0.470, P=0.000), Aβ 1-42/ Aβ 1-40( r=0.479, P=0.000)and P-Tau 181( r=0.371, P=0.000)in the AD-SD group at baseline.Multivariate Logistic regression model showed that serum Aβ 1-42 and P-Tau 181 levels and HRSD had predictive effects on changes in sleep quality in AD patients( OR=1.897, 1.269 and 1.889, P=0.000, 0.003 and 0.000). The areas under the receiver operating characteristic(ROC)curves for Aβ 1-42, P-Tau 181 and HRSD were 0.926(95% CI 0.860-0.991), 0.837(95% CI 0.746-0.927)and 0.854(95% CI 0.776-0.932), respectively. Conclusions:Sleep quality is correlated with serum Aβ 1-42and P-Tau 181 levels in AD patients.Elevated serum levels of Aβ 1-42 and P-Tau 181 and high HRSD scores are important predictors of SD in AD patients and may be used as indexes for clinical treatment efficacy.