Sudeep S. Gill, MD, MSc
Do high-dose vitamin B supplements reduce rate of cognitive decline in mild-to-moderate Alzheimer disease (AD)?
Randomized placebo-controlled trial (RCT). Clinicaltrials.gov NCT00056225.
Blinded (patients, caregivers, clinicians, and psychometrists).†
Every 3 months, up to 18 months.
40 centers in the USA.
409 patients > 50 years of age (mean age 76 y, 56% women) who had probable AD, scored 14 to 26 on the Mini–Mental State Examination (MMSE), and were medically stable. Exclusion criteria were vitamin B12 levels < 129 pmol/L (175 pg/mL), folate levels < 9.5 nmol/L (4.2 ng/mL), renal insufficiency (serum creatinine levels ≥ 176.8 µmol/L [2.0 mg/dL]), use of daily vitamin supplements with > 400 µg folic acid, or regular use of any of the following in the past 2 months: sedatives, drugs with significant central anticholinergic effects, anti-Parkinsonian medications, or investigational treatments for AD.
Folic acid, 5 mg/d, vitamin B12 (cyanocobalamin), 1 mg/d, and vitamin B6 (pyridoxine hydrochloride), 25 mg/d (n = 240), or placebo (n = 169).
Included 18-month change in AD Assessment Scale cognitive subscale, MMSE, AD Cooperative Study Activities of Daily Living scale, Clinical Dementia Rating sum of boxes, Neuropsychiatric Inventory, and homocysteine levels.
84% (99% in intention-to-treat analysis).
At a median follow-up of 18 months, vitamin B supplements reduced homocysteine levels more than placebo (mean change −2.42 vs −0.86 µmol/L [−0.33 vs −0.12 mg/L], P < 0.001). Groups did not differ for rate of change in cognitive outcomes (Table).
High-dose vitamin B supplements did not slow cognitive decline in mild-to-moderate Alzheimer disease.
High-dose vitamin B supplements vs placebo in mild-to-moderate Alzheimer disease (AD)‡
‡ADAS = AD Assessment Scale; ADCS-ADL = AD Cooperative Study Activities of Daily Living; CDR = Clinical Dementia Rating; MMSE = Mini-Mental State Examination; NPI = Neuropsychiatric Inventory.
§Lower scores = better for all scales, except MMSE and ADCS-ADL.
||For rate of change over 18 mo using generalized estimating equations method.
Gill SS. High-dose vitamin B supplements did not slow cognitive decline in mild-to-moderate Alzheimer disease. Ann Intern Med. ;150:JC2–7. doi: 10.7326/0003-4819-150-4-200902170-02007
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Published: Ann Intern Med. 2009;150(4):JC2-7.
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