Signs of impaired cognitive function in adolescents with marginal cobalamin status

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Abstract

Lack of cobalamin may lead to neurologic disorders, which have been reported in strict vegetarians. The objective of this study was to investigate whether cognitive functioning is affected in adolescents (aged 10-16 y) with marginal cobalamin status as a result of being fed a macrobiotic diet up to an average age of 6 y. Data on dietary intake, psychological test performance, and biochemical variables of cobalamin status were collected from 48 adolescents who consumed macrobiotic (vegan type) diets up to the age of 6 y, subsequently followed by lactovegetarian or omnivorous diets, and from 24 subjects (aged 10-18 y) who were fed omnivorous diets from birth onward. Thirty-one subjects from the previously macrobiotic group were cobalamin deficient according to their plasma methylmalonic acid concentrations. Seventeen previously macrobiotic subjects and all control subjects had normal cobalamin status. The control subjects performed better on most psychological tests than did macrobiotic subjects with low or normal cobalamin status. A significant relation between test score and cobalamin deficiency (P: = 0.01) was observed for a test measuring fluid intelligence (correlation coefficient: -0.28; 95% CI: -0.48, -0.08). This effect became more pronounced (P: = 0.003) within the subgroup of macrobiotic subjects (correlation coefficient: -0.38; 95% CI: -0.62, - 0.14). Our data suggest that cobalamin deficiency, in the absence of hematologic signs, may lead to impaired cognitive performance in adolescents.

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Long-term developmental outcome of infants with iron deficiency.

B. Lozoff, E. Jimenez, A Wolf (1991)

Iron-deficiency anemia has been associated with lowered scores on tests of mental and motor development in infancy. However, the long-term developmental outcome of infants with iron deficiency is unknown, because developmental tests in infancy do not predict later intellectual functioning. This study is a follow-up evaluation of a group of Costa Rican children whose iron status and treatment were documented in infancy. Eighty-five percent (163) of the 191 children in the original group underwent comprehensive clinical, nutritional, and psychoeducational assessments at five years of age. The developmental test battery consisted of the Wechsler Preschool and Primary Scale of Intelligence, the Spanish version of the Woodcock-Johnson Psycho-Educational Battery, the Beery Developmental Test of Visual-Motor Integration, the Goodenough-Harris Draw-a-Man Test, and the Bruininks-Oseretsky Test of Motor Proficiency. All the children had excellent hematologic status and growth at five years of age. However, children who had moderately severe iron-deficiency anemia as infants, with hemoglobin levels less than or equal to 100 g per liter, had lower scores on tests of mental and motor functioning at school entry than the rest of the children. Although these children also came from less socioeconomically advantaged homes, their test scores remained significantly lower than those of the other children after we controlled for a comprehensive set of background factors. For example, the mean (+/- SD) adjusted Woodcock-Johnson preschool cluster score for the children who had moderate anemia in infancy (n = 30) was 448.6 +/- 9.7, as compared with 452.9 +/- 9.2 for the rest of the children (n = 133) (P less than 0.01); the adjusted visual-motor integration score was 5.9 +/- 2.1, as compared with 6.7 +/- 2.3 (P less than 0.05). Children who have iron-deficiency anemia in infancy are at risk for long-lasting developmental disadvantage as compared with their peers with better iron status.

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Neurologic aspects of cobalamin deficiency.

E B Healton, D G Savage, J C Brust … (1991)

We reviewed 153 episodes of cobalamin deficiency involving the nervous system that occurred in 143 patients seen over a recent 17-year period at 2 New York City hospitals. Pernicious anemia was the most common underlying cause of the deficiency. Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient. In 42 (27.4%) of the 153 episodes, the hematocrit was normal, and in 31 (23.0%), the mean corpuscular volume was normal. Neutropenia and thrombocytopenia were unusual even in anemic patients. In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery. Followup evaluation was adequate to assess the neurologic response to vitamin B12 therapy in 121 episodes. All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment was strongly related to that before therapy as well as to the duration of symptoms. The percent improvement over baseline neurologic status after treatment was inversely related to duration of symptoms and hematocrit. Some evidence of response was always seen during the first 3 months of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

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Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls.

Katherine Duggan, Samuel Casella, Karim Brandt … (1996)

Up to 25% of adolescent girls in the USA are iron deficient. This double-blind, placebo-controlled clinical trial assessed the effects of iron supplementation on cognitive function in adolescent girls with non-anaemic iron deficiency. 716 girls who enrolled at four Baltimore high schools were screened for non-anaemic iron deficiency (serum ferritin < or = 12 micrograms/L with normal haemoglobin). 98 (13.7%) girls had non-anaemic iron deficiency of whom 81 were enrolled in the trial. Participants were randomly assigned oral ferrous sulphate (650 mg twice daily) or placebo for 8 weeks. The effect of iron treatment was assessed by questionnaires and haematological and cognitive tests, which were done before treatment started and repeated after the intervention. We used four tests of attention and memory to measure cognitive functioning. Intention-to-treat and per-protocol analyses were done. Of the 81 enrolled girls with non-anaemic iron deficiency, 78 (96%) completed the study (39 in each group). Five girls (three control, two treatment) developed anaemia during the intervention and were excluded from the analyses. Thus, 73 girls were included in the per-protocol analysis. Ethnic distribution, mean age, serum ferritin concentrations, haemoglobin concentrations, and cognitive test scores of the groups did not differ significantly at baseline. Postintervention haematological measures of iron status were significantly improved in the treatment group (serum ferritin 27.3 vs 12.1 micrograms/L, p < 0.001). Regression analysis showed that girls who received iron performed better on a test of verbal learning and memory than girls in the control group (p < 0.02). In this urban population of non-anaemic iron-deficient adolescent girls, iron supplementation improved verbal learning and memory.

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Journal

Title: The American Journal of Clinical Nutrition

Publisher: Oxford University Press (OUP)

ISSN (Print): 0002-9165

ISSN (Electronic): 1938-3207

Publication date Created: September 2000

Publication date Created: September 01 2000

Publication date Other: September 2000

Publication date (Print): September 01 2000

Volume: 72

Issue: 3

Pages: 762-769

Affiliations

[1 ]From the Division of Human Nutrition and Epidemiology, Wageningen Agricultural University, Wageningen, Netherlands; the Department of Nutritional Epidemiology, Organisation for Applied Sciences, Nutrition and Food Research Institute, Zeist, Netherlands; the Department of Psychology, Tilburg University, Tilburg, Netherlands; the Laboratory of Endocrinology and Reproduction, University Hospital St

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DOI: 10.1093/ajcn/72.3.762

PubMed ID: 10966896

SO-VID: 8c789bb3-cd8f-42b9-acac-3033ae05e193

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Signs of impaired cognitive function in adolescents with marginal cobalamin status

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Probing cerebral hemodynamics with BOLD fMRI

Most cited references 21

Long-term developmental outcome of infants with iron deficiency.

Neurologic aspects of cobalamin deficiency.

Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls.

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