Efficiency of Donepezil in Elderly Patients for Prevention of POCD Dysfunction

Study Overview
=================
Brief Summary
-----------------
Postoperative cognitive dysfunction (POCD) occurs mainly in aged patients. POCD may increase the mortality and morbidity. However, the mechanism of POCD is not clear yet and no effective therapy method was proved. According to our previous study, the central cholinergic system impaired by the anesthesia and surgery play a very important role in the POCD and donepezil an acetylcholinesterase inhibitor can prevent the POCD after isoflurane anesthesia in aged mice. Donepezil is a commercial medicine used for the Alzheimer Disease, which is tolerable and has minimal adverse events. In present study a multi-center randomized case control study was conducted and we hypothesized that donepezil attenuate the POCD.

Official Title
-----------------
Efficiency of Donepezil in Elderly Patients Undergoing Orthopedic Surgery Due to Underlying Postoperative Cognitive Dysfunction, a Multicenter Randomized Controlled Trial

Conditions
-----------------
Total Knee Arthroplasty, Fracture of Head of Femur Articular Displaced, Protrusion of Intervertebral Disc

Intervention / Treatment
-----------------
* Drug: Donepezil
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Elder than 60 years old Speak Chinese Mandarin Scheduled to undergo hip or knee replacement surgery and lumbar spine surgery The operation time is more than 2 hours. Signed the informed consent American Society of Anesthesiologists (ASA) classification I-II Exclusion Criteria: Existing cerebral disease, or have a history of neurological and psychiatric diseases including Alzheimer Disease, stroke, epilepsy and psychosis Existing cognitive impairment as evidenced by Mini-Mental State Examination scores below 24 Several audition or vision disorder Patients with tumors or infections Unwillingness to comply with the protocol or procedures Can not communicate normally in Mandarin Chinese Existing bradycardiac arrhythmia (Heart rate <60 bpm for any reasons) Existing gastrointestinal ulcer Existing urinary incontinence Existing asthma or chronic obstructive pulmonary disease Postoperative admission to ICU Allergic to donepezil

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br> | Drug: Placebo<br>* Placebo, 1 pill/ day for 7 days Po, was administrated from the day before surgery.<br>|
| Experimental: Donepezil<br> | Drug: Donepezil<br>* Donepezil a cholinesterase inhibitor, 5mg(1 pill)/ day for 7 days Po, was administrated from the day before surgery.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of POCD after the surgery. |  | up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of postoperative delirium after surgery. |  | 1 to 7 days after surgery | 
| POCD incidence one month, six months and one year after surgery. |  | one month, six months and one year after surgery |