Due to slow recruiment. Only 40 patients were recruited in four years.

This study will recruit patients more than 65 years old eligible for non-cardiac surgery. Patients who participate will take either vitamin B12 and folic acid supplementation or placebo for 7 days before surgery. Neuropsychological test battery (NPB) will be tested before intervention and at discharge for determination of Post operative cognitive dysfunction (POCD). Another group of non-surgical elderly participants will also be tested for NPB to account for learning effect in POCD diagnosis. The hypothesis is that preoperative vitamin B12 supplementation will reduce the incidence of POCD in elderly patients undergoing non-cardiac surgery.

Vitamin B12 has long been suggested to have neural nutrient effect and widely used in clinical settings for patients with peripheral nerve injury as well as complementary medicine for patients with CNS disorders, including cognitive dysfunction. Evidences showed that, although no significant improvement in cognitive function was observed in healthy elderly after vitamin B12 supplementation, some studies suggested that patients with pre-existing CNS disorder may benefit from Vitamin B12. Post operational cognitive dysfunction (POCD) is severe, and long-lasting complication that affects as high as 53% of patients in high risk surgeries. Age is an independent risk factor for POCD. Researches have shown that serum vitamin B12 level decrease with age, and methylcobalamin (active form of Vitamin B12) content in the frontal cortex of aged patients are lower than that of younger patients. However, there are no report on effect of preemptive supplementation of vitamin B12 on POCD incidence. Therefore, the current research is aimed to explore the preoperative methylcobalamin supplementation (500 mg, 3/day for 7 days before surgery) on incidence of POCD. Folic acid supplementation is a common companion for vitamin B12 treatment in clinical settings because they are in the same methionine cycle, increase of one may result in deficiency of another. So we added 5 mg, 1/day of folic acid with methylcobalamin in the treatment group.

This study will recruit patients more than 65 years old eligible for non-cardiac surgery. Patients who participate will take either vitamin B12 and folic acid supplementation or placebo for 7 days before surgery. Neuropsychological test battery (NPB) will be tested before intervention and at discharge for determination of Post operative cognitive dysfunction (POCD). Another group of non-surgical elderly participants will also be tested for NPB to account for learning effect in POCD diagnosis. The hypothesis is that preoperative vitamin B12 supplementation will reduce the incidence of POCD in elderly patients undergoing non-cardiac surgery.

Inclusion Criteria:

• 1. Age equals or over 65
• 2. Scheduled for spinal or joint replacement surgery under general anesthesia，estimated surgery time over 2h.
• 3. Signed written informed consent obtained
• 4. Non-surgical Controls are age and sex - matched community elderly residents.

Exclusion Criteria:

• 1. Disease of the central nervous system that impairs cognitive function, including all kinds of dementia, and depression
• 2. MMSE score < 24
• 3. Received education for less than 5 years
• 4. Currently taking sedative or antidepressant drugs
• 5. Has taken vitamin B12, folic acid or their derivatives (methycobalamin, cobalamin, tetrahydrofolic acid, etc.) within 6 months.
• 6. Has accepted cardiac or neurological surgery within one year.
• 7. Was admitted for other clinical trials within 3 month
• 8. Patients that regularly taking drugs that affect vitamin B absorption, including colchicine, neomycin, salicylate.
• 9. Has severe visual or auditory problems
• 10. Alcohol or drug dependent (alcohol dependent: drank more than 100 mL of Chinese liqueur with alcohol concentration over 40% everyday for the past 3 months).
• 11. Patients that are already admitted for this study can not be admitted the second time, no matter the cause of surgery

Central randomization. Groups are marked as A and B with no participants, care provider, investigator and outcome assessors know which group is the drug and which is the placebo. Placebo are made as tablets that mimics the color, shape and size of the drugs.