Introduction: Postoperative delirium (POD), an acute, transient, fluctuating disturbance in attention, cognition, and level of consciousness, is a common (15-53%) postoperative complication, and it is associated with longer hospital stays, worse functional outcomes, higher healthcare costs, and increased mortality. However, at the current time, effective prevention and treatment are not only hampered by lack of knowledge about the neuropathogenesis of POD but also by a lack of biomarkers that could predict individual risk and assess diagnosis and severity of POD.

Recent studies have focused on inflammatory markers (IL-1, IL-6, IL-8, IL-10, CRP), Alzheimer's disease-related factors (Tau, Aβ40/42), and nerve injury factors (S100β, NSE), but failed to establishing causality between these markers and POD. Furthermore, these results were contradictory. Previous study of the investigators found that the dysregulation of preoperative microRNA (miR)-146a and miR-181c in cerebrospinal fluid (CSF) and serum was associated with the development and severity of POD. Therefore, the investigators hypothesized these neurimmiRs and other neuro-epigenetics biomarkers might participate in the neuropathogenesis of POD.

Purpose: Aims to search for neuro-epigenetics biomarkers to predict and diagnose POD.

Method:

1. Study design: This study is a prospective investigation that searches for neuro-epigenetics biomarkers to predict and diagnose POD.
2. Inclusion criteria / Exclusion Criteria

Inclusion criteria: Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.

Exclusion Criteria:

1. a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);
2. Patients diagnosed with malignant or benign tumors;
3. Mini-Mental State Examination (MMSE) scores of 26 or less;
4. American Society of Anesthesiologists (ASA) score [a global score that assesses the physical status of patients before surgery, ranging from 1 (normal health) to 5 (moribund)] greater than 3;
5. a history of alcohol abuse and drug dependence;
6. inability to read or severe visual or auditory deficits;
7. unwillingness to comply with the protocol or procedures.

Inclusion Criteria: Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.

Exclusion Criteria:

1. a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);
2. patients diagnosed with malignant or benign tumors;
3. Mini-Mental State Examination (MMSE) scores of 26 or less;
4. American Society of Anesthesiologists (ASA) score greater than 3;
5. a history of alcohol abuse and drug dependence;
6. inability to read or severe visual or auditory deficits;
7. unwillingness to comply with the protocol or procedures.

Patients were at least 65 years old and were scheduled to have hip/knee replacement.