Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: Background: Older diabetic people are at greater risk of cognitive decline than non-diabetic people. Vitamin B12 deficiency in older people is associated with cognitive impairment and Alzheimer's disease. Vitamin B12 deficiency may therefore contribute to cognitive decline in older diabetic people.

Objective: To determine whether the correction of mild vitamin B12 deficiency in cognitively normal older diabetic people reduces the incidence of cognitive decline.

Design: randomized, double blind, placebo controlled trial Subject: Cognitively normal diabetic outpatients aged 70 years or older with plasma vitamin B12 150-300 pmol/L in medical and family medicine/ general outpatient clinics.

Procedure: After excluding those with clinical manifestations of vitamin B12 deficiency and without family member who can reliably inform on cognitive functioning (personal contact at least once a week), eligible patients will be invited to participate in this clinical trial. After obtaining written consent, research assistant (RA) will record demographic and clinical information from the subjects and perform neuropsychological tests - 1. Clinical dementia rating scale (CDR), 2. neurocognitive test battery (see below) 3. Chinese Mini mental state examination (MMSE), 4. Geriatric depression scale (GDS). Fasting blood will be taken for serum methylmalonic acid (MMA). Those with cognitive impairment and significant comorbidities will be excluded.

264 eligible subjects will be randomly assigned to take either two Vitamin B12 500 microgram or two identical looking placebo tablets once daily for 27 months.

All subjects or family caregivers are reviewed in the research clinic every 12 weeks in which the research assistant performs a pill count and dispenses the trial tablets. At 9 monthly intervals, the subjects will have neurocognitive test battery repeated at research clinic. CDR will be repeated at month 18 and 27. At month 9 and 27, fasting serum MMA and vitamin B12 will be repeated.


Options:
A: Inclusion Criteria:

* Patients presenting within one months of ischemic stroke (ischemic or hemorrhagic) or TIA
* Homocysteine level ≥ 15μmol／L
* Agree to take study medication;Be geographically accessible for follow-up
* Provide written informed consent

Exclusion Criteria:

* Other cause of ischemic stroke (cardioembolism; stroke of other determined etiology, and stroke of undetermined etiology according to TOAST subtypes) or hemorrhagic stroke (intracranial vascular malformations; cerebral amyloid angiopathy; trauma and bleeding disorders etc)
* Use of vitamin supplements containing folate, B6 or B12
* Pregnancy or women of child-bearing potential who are at risk of pregnancy
* Limited life expectancy
B: Inclusion Criteria:

* 50-70 years
* Men and post-menopausal women
* Women with a surgically removed uterus were required to be \>=55 years

Exclusion Criteria:

* Plasma total homocysteine \<13 or \>26 umol/L
* Serum vitamin B12 \<200 pmol/L
* Self-reported current use of drugs which affect folate metabolism
* Self-reported current use of drugs believed to influence intima-media thickening, i.e., lipid-lowering drugs, hormone replacement therapy
* Self-reported medical diagnosis of renal, intestinal, thyroid disease
* Self-reported medical diagnosis of current cancer
* Self-reported current use of supplements containing B vitamins
* Self-reported inability or unwillingness to fast for 12 hours
* \<80% compliance using placebo pills during a 6-week run-in period
* Not giving written informed consent
* Participation in other research studies
C: Inclusion Criteria:

* \>/= 70 years old
* B12: 150 - 300 pmol/L
* Caregiver (personal contact at least once a week)

Exclusion Criteria:

* Dementia
* Peripheral neuropathy
* Anaemia (Hb\<10 g/dl)
* Renal failure (creatinine \> 150 µmol/L
* Stroke
D: Inclusion Criteria:

1. Diagnoses of possible or probable Alzheimer's disease (NINCDS-ADRDA)
2. Presence of a caregiver (friend or relative) who can assume responsibility for medication compliance, can accompany the patient to all visits, and rate patient's condition
3. Written informed consent from both the patient (or surrogate) and caregiver
4. An MMSE score between 12 and 26 inclusive
5. Administration of a maintenance dosage of donepezil (5-10mg/d), rivastigmine (6-12mg/d) or rivastigmine (Exelon) patch (4.6 mg or 9.5 mg), galantamine or galantamine ER (16-24mg/d) for a minimum of 4 weeks prior to randomization
6. Agreement not to take vitamin E supplements and/or memantine outside of the study (daily multivitamin is permitted containing up to 100 IU alpha-tocopherol)

Exclusion Criteria:

1. A non-Alzheimer primary dementia (e.g., vascular dementia, Lewy body dementia, fronto-temporal dementia, vitamin B-12 deficiency, hypothyroidism)
2. Current major depression, delirium, alcohol or psychoactive substance abuse or dependency, schizophrenia, or delusional disorder as defined by DSM-IV
3. Presence of any uncontrolled systemic illness that would interfere with participation in the study or a life expectancy of less than one year
4. Pregnant or intention to become pregnant
5. Enrollment in another interventional clinical trial
6. Current prescription with more than one AChE inhibitor
7. Current prescription for warfarin
8. Use of vitamin E supplements in the past 2 weeks
9. Use of memantine in the past 4 weeks or known intolerance
10. Estimated creatinine clearance less than 5ml/min (Cockcroft-Gault formula)
11. Use of amantadine in the past 2 weeks

Answer: C