Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial.

BACKGROUND: Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms. METHODS: In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function. RESULTS: The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%). CONCLUSIONS: Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.

Three-month nutritional supplementation in Indonesian infants and toddlers benefits memory function 8 y later.

Does short-term supplementary feeding during infancy and childhood have long-lasting effects? In 1986, 334 children aged 6-60 mo living on rural tea plantations in West Java, Indonesia, participated in a 3-mo randomized trial to test the effects of a dietary supplement providing approximately 1672 kJ (400 kcal) energy/d, with about the same nutrient density as local foods. We returned to the same communities in 1994 and enrolled 231 (125 supplemented, 106 control) of the original subjects in a follow-up study of the long-term effects of supplementation. We assessed these subjects by using several measures: anthropometry, iron status, information processing, Peabody Picture Vocabulary Test, word fluency, and an arithmetic test. The supplemented group showed no differences from those in the control group. However, when the analysis was limited to subjects who had received the supplement before the age of 18 mo (n = 73), the supplemented children performed better than control children on the Sternberg test of working memory (decision time intercept: probe absent, P = 0.002; probe present, P = 0.053). After considering possible confounders, we concluded that the supplementation during infancy was responsible for the difference. This finding shows that supplementation can have long-lasting effects on a specific domain if the child receives it at the appropriate stage of development.

PIP: This study sought to determine whether short-term supplementary feeding during infancy and childhood has long-lasting effects. In 1986, 334 children aged 6-60 months living on rural tea plantations in West Java, Indonesia, participated in a 3-month randomized trial to test the effects of a dietary supplement providing approximately 1672 kJ (400 kcal) energy/day, with about the same nutrient density as local foods. The authors returned to the same communities in 1994 and enrolled 231 (125 supplemented, 106 control) of the original subjects in a follow-up study of the long-term effects of supplementation. They assessed these subjects by using several measures: anthropometry, iron status, information processing, Peabody Picture Vocabulary Test, word fluency, and an arithmetic test. The supplemented group showed no differences compared to the control group. However, when the analysis was limited to subjects who had received the supplement before the age of 18 months (n = 73), the supplemented children performed better than control children on the Sternberg test of working memory (decision time intercept: probe absent, P = 0.002; probe present, P = 0.053). After considering possible confounders, the authors concluded that the supplementation during infancy was responsible for the difference. This finding shows that supplementation can have long-lasting effects on a specific domain, if the child receives it at the appropriate stage of development.

"Stupidity or worms": do intestinal worms impair mental performance?

The title of a 1930s article asked the question, "Stupidity or Hookworm?" In this article, the authors discuss research that attempts to answer the question of whether intestinal worms--namely, hookworm, whipworm, and roundworm--harm the mental performance of their hosts. After introducing the biology and epidemiology of intestinal worms, the authors present the historical background to the problem. They review research from the 1910s through the 1990s; there is evidence that high intensities of worms can affect mental performance, but not all dewormed children show improved performance. They discuss the mechanisms of how worms might affect the mind.

Effect of removing Ascaris on the growth of Guatemalan schoolchildren.

OBJECTIVE: To determine whether successful deworming for 6 months in children with high levels of Ascaris improves physical growth. SUBJECTS: Two hundred twenty-eight children (mean age, 9.7 years) in a highland Indian town in Guatemala. DESIGN: Children were randomly assigned to receive albendazole or placebo at baseline and 12 weeks. Children and field workers were both blind to the group assignment. OUTCOME MEASURES: Children's heights, weights, and mid-upper-arm circumferences were measured at baseline and 12 and 24 weeks. Fecal egg counts were taken at 0, 2, 12, 14, and 24 weeks to estimate the helminth burden (eggs per gram of feces [epg]). RESULTS: Baseline helminth prevalences were Ascaris, 91%, and Trichuris, 82%. Ascaris intensities were high: half of the children had moderate burdens (10 000 to 50 000 epg), and 25% had heavy burdens ( > 50 000 epg). Trichuris burdens were light (72% < 1000 epg). The albendazole and placebo groups did not differ at baseline in epg, age, anthropometry, or socioeconomic status. The two rounds of treatment successfully reduced the Ascaris burdens but had less effect on Trichuris. At 6 months the treatment group showed a small gain in weight (0.18 kg) compared with the placebo group but no improvement in height or mid-upper-arm circumference. CONCLUSIONS: The successful removal of ascaris in a population of school-aged children with relatively high loads may have modest effects on weight gain. Ascaris is one of the most common infections in school-aged children, but its effect on the host may be less than that of other helminths.

The effects of deworming on indicators of school performance in Guatemala.

Intestinal helminths are among the most common infections in school-age children. Of 246 children, aged 7-12 years, attending school in rural Guatemala, 91% carried Ascaris lumbricoides and 82% carried Trichuris trichiura. These children were randomly assigned to receive either albendazole or placebo at 0 and 12 weeks in a 'double-blind' study of the effects of deworming on indicators of school performance. Albendazole successfully rid the children of Ascaris but it was less effective against Trichuris. The children's performance in tests of reading and vocabulary were measured at 0 and 24 weeks, the Peabody picture vocabulary test was given at 24 weeks, and attendance was measured throughout the school year. Comparison of the treated and placebo groups showed no positive effect of deworming. The treated children were largely free of Ascaris for at least 6 months, but during that period we could not detect any improvement in reading, vocabulary, or attendance. The effects of being Trichuris-free were not examined because of the limited effectiveness of albendazole against this worm at the dosage used.

Adverse effect of iron supplementation on weight gain of iron-replete young children.

The efficacy of iron supplementation for iron-deficient subjects is in no doubt. However, the assumption that iron supplementation of iron-replete subjects is harmless may not be valid. We have studied the effect of iron supplementation on growth rate in 47 iron-sufficient young children (12-18 months) in Indonesia. The children were randomly assigned either ferrous sulphate (3 mg/kg daily) or placebo every day for 4 months. Before treatment the length, weight, and arm circumference of the two groups were similar. During the 4 months of supplementation the rate of weight gain was significantly greater in the placebo group than in the iron-supplemented group (0.106 [SE 0.010] vs 0.070 [0.011] kg every 2 weeks, p = 0.02). The rates of gain in length and arm circumference did not differ significantly by treatment. There were no differences between the groups in rates of respiratory and gastrointestinal infections. These results suggest that iron supplementation of iron-replete children may retard their growth.

Characteristics of 16-dehydroprogesterone reductase in cell extracts of the intestinal anaerobe, Eubacterium sp. strain 144.

16-Dehydroprogesterone reductase (16-DHPR) activity was present in cell extracts of Eubacterium sp. strain 144 only when the organism was grown in the presence of steroids containing a delta 16-17 double bond and C-20-ketone. Cells grown with 16-dehydropregnenolone contained 16-DHPR activity but lacked delta 4-5-3-keto steroid reductase activity. Pyruvate or sodium dithionite served as electron donors for 16-DHPR and both reactions required methyl viologen as an electron carrier. Neither NADH nor NADPH, with or without flavin nucleotides, were used by 16-DHPR. Enzyme activity was detected in the cytoplasmic fraction (40%) and membrane fraction (20%) of crude cell extracts, but 40% of the activity was unaccounted for following ultracentrifugation. 16-DHPR activity was unaffected by pH in potassium phosphate buffer over the range 5.0 to 8.5, but was inhibited by Tris-HCl above pH 7.0. 16-DHPR activity was inhibited by sulfhydryl reagents, but inhibitors of electron transport reactions or metal chelators did not affect the enzyme.