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.
