Vitamin B12 Supplement to Prevent Cognitive Decline

Study Overview
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Brief Summary
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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.

Conditions
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Cognitive Decline

Intervention / Treatment
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* Dietary Supplement: Vitamin B12
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin B12<br>Vitamin B12, 1mg, daily, 27 months | Dietary Supplement: Vitamin B12<br>* 2 tablets<br>|
| Placebo Comparator: Placebo<br>Placebo comparator | Dietary Supplement: Placebo<br>* 2 tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical Dementia Rating Scale (CDR) |  | Change from baseline in CDR at month 9, 18, 27 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Neurocognitive test battery (NTB) score | NTB including tests of executive funciton, psychomotor speed and memory | Change from baseline in NTB score at month 9, 18, 27 | 
| Change in serum homocysteine (µmol/L) |  | Change from baseline in serum homocysteine at month 9, 27 |