Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels

Abstract

Background. Low serum cobalamin levels are often found in apparently normal older subjects. A major worry of leaving cobalamin de®ciency untreated is that it may lead to subtle deterioration in cognitive function.Objectives. To investigate the eect of supplementation on the cognitive function of older people with cobalamin de®ciency by a randomized trial.Methods. Fifty Chinese subjects more than 60 years old with serum cobalamin level 5120 pmol/l were randomized into supplement and control groups. Fasting serum methylmalonic acid levels (MMA) were measured. A battery of neuropsychological tests was administered. The supplement group received intramuscular cyanocobalamin injections, while the control group received no intervention. They were followed up at around 4 months.Results. 78% of the subjects had raised MMA, indicating metabolic cobalamin de®ciency. Supplemented subjects improved in performance IQ, but the amount of improvement was not signi®cantly more than that of control subjects. Moreover, the supplement group fared worse than the control group at follow-up in some motor function scores. Three out of seven demented subjects had improvement in Mini-Mental State Examination scores, but there was no consistent improvement in other neuropsychological scores.Conclusions. This study suggested that cobalamin de®ciency did not invariably cause cognitive impairment in older people. There remain the possibilities that cobalamin de®ciency causes cognitive impairment or exacerbates coexisting dementia in some older people. #

Metabolic Markers of Cobalamin Deficiency and Cognitive Function in Normal Older Adults

“…Although a relationship between elevated tHcy and reduced cognitive function is biologically plausible, other studies have shown divergent results and failed to confirm the above findings. [24][25][26][27] Levels of tHcy are dependent on folic acid and Cbl functions. The prevalence of elevated tHcy in the current study's population was low, likely because of normal or above-normal levels of RBC folate after national folic acid supplementation of wheat products, the exclusion of subjects with history of cerebrovascular disease in the study (although subjects with cardiovascular history were included), and perhaps the fact that samples were taken in a nonfasting state.…”

Vitamin B12, folate, and Alzheimer's disease

“…Discordant results have been found in general (Table 3) that may be caused by the differences in study design (patients only, both cases and controls), the levels for defining deficiency before treatment, as well as the dosage, duration, and the manner of treatment (intramuscular injection, oral). In spite of these, a treatment effect on cognitive functioning and among subjects with mild, or a short history of, dementia [Martin et al, 1992;Cunha et al, 1995;Eastley et al, 2000;Nilsson et al, 2000Nilsson et al, , 2001 but not among severe or mixed severity of dementia patients [Carmel et al, 1995;Teunisse et al, 1996;Kwok et al, 1998], has been demonstrated.…”

“…After vitamin replacement, patients with mild or moderate dementia and elevated plasma homocysteine levels improved cognition clinically, while severely demented patients and patients with normal plasma homocysteine levels did not. Kwok et al [1998] carried out a randomized study in Hong Kong in which 50 subjects age 60 and above with serum cobalamin level o120 pmol/L were randomized into supplement and control groups. The supplement group received intramuscular cyanocobalamin injections and were followed up for 4 months.…”

Diet, nutrients and metabolism: cogs in the wheel driving Alzheimer's disease pathology?

“…The link between elevated homocysteine and AD risk has been firmly established in several studies ( 147 , 163 , 164 ) , and homocysteine levels are also correlated to vitamin B 6 , B 12 and folate status ( 165 – 167 ) ; however, the exact mechanisms underlying the elevated homocysteine, connected metabolites and AD, remain to be fully elucidated. It is probable that elevated homocysteine promotes AD by more than one mechanism, and while homocysteine serves as a surrogate marker for nutrient status (which when deficient can promote neurological damage in its own right), evidence suggests that homocysteine has direct actions on the brain.…”