WITHDRAWN: Sleep Treatment Improves Neuropsychological Symptoms and Reduces Blood Aβ42/pTau Protein in Alzheimer's Disease Patients: a Longitudinal Study

Abstract

Background: Amyloid β peptide-42 (Aβ42) and phosphorylated Tau on Threonine 181 (Tau-pT181) are the core biomarkers in Alzheimer’s disease. Accumulated evidence showed an aberrant elevation of these biomarkers due to sleep disturbance. However, it is not clear if improving sleep quality reduces Aβ42 and Tau-pT181 in Alzheimer’s disease patients.Methods: A longitudinal study was conducted on 126 patients with mild-moderate dementia due to Alzheimer’s disease. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Behavioral and neuropsychological assessment was conducted using multiple self-reporting questionnaire score systems. Aβ42 and Tau-pT181 levels in blood specimens were measured using an ELISA assay kit. All patients received Donepezil treatment for Alzheimer’s disease. Sleep disorders were individually managed with either medication or physical therapy according to their symptom categories.Results: Of the 126 cases, 93 (73.8%) patients were diagnosed with sleep disorders. The PSQI scores significantly correlated with depression and anxiety scores, as well as Aβ42 and Tau-pT181 levels. Also, a significant correlation was found among depression, anxiety, Aβ42 and Tau-pT181 in all patients. Sleep intervention drastically reduced PSQI score, as well as Aβ42 and Tau-pT181 levels, in parallel with improved cognition, deterioration and anxiety scores. Dementia and depression scores were improved only in patients who completely recovered (PSQI < 7) after sleep treatment. There was a 35.9% reduction of Aβ42 levels and a 32.8% reduction of Tau-pT181 levels in this subgroup of patients (56 cases). Conversely, the reduction extent was only 6.9% for Aβ42 and 12.2% for Tau-pT181 in patients who did not completely recover (PSQI ≥ 7 post treatment, 37 cases). Multiple logistic regression analysis revealed that Aβ42 level is the strongest risk factor for sleep disorder incidence and incomplete recovery after sleep treatment.Conclusion: Sleep quality score is associated with patient depression and anxiety status, as well as blood Aβ42 and Tau-pT181 levels. A complete recovery is critical for a full improvement of all behavioral and neuropsychological assessments, which is also associated with a deep reduction of Aβ42 and Tau-pT181 levels. Aβ42 level is a prognostic factor for a diagnosis of sleep disorder and treatment responsiveness.