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Results of 2-year vitamin B treatment on cognitive performance
Zwaluw, N.L. van der; Dhonukshe-Rutten, R.A.M. ; Wijngaarden, J.P. van; Brouwer, E.M. ; Rest, O. van de; Veld, P.H. in 't; Enneman, A.W. ; Dijk, S.C. van; Ham, A.C. ; Swart, K.M.A. ; Velde, N. van der; Schoor, N.M. van; Cammen, T.J.M. van der; Uitterlinden, A.G. ; Lips, P. ; Kessels, R.P.C. ; Groot, C.P.G.M. de - \ 2014
Neurology 83 (2014)23. - ISSN 0028-3878 - p. 2158 - 2166.
folic-acid supplementation - randomized controlled-trial - placebo-controlled trial - alzheimers-disease - elderly-patients - double-blind - homocysteine - metaanalysis - impairment - folate
Objective: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels. Methods: This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet. Both tablets contained 15 µg vitamin D3. Data were available for global cognitive functioning assessed by Mini-Mental State Examination (n = 2,556), episodic memory (n = 2,467), attention and working memory (n = 759), information processing speed (n = 731), and executive function (n = 721). Results: Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95% confidence interval -5.3 to -4.7) µmol/L in the B-vitamin group and 1.3 (-1.6 to -0.9) µmol/L in the placebo group. Cognitive domain scores did not differ over time between the 2 groups, as determined by analysis of covariance. Mini-Mental State Examination score decreased with 0.1 (-0.2 to 0.0) in the B-vitamin group and 0.3 (-0.4 to -0.2) in the placebo group (p = 0.05), as determined by an independent t test. Conclusions: Two-year folic acid and vitamin B12 supplementation did not beneficially affect performance on 4 cognitive domains in elderly people with elevated Hcy levels. It may slightly slow the rate of decline of global cognition, but the reported small difference may be attributable to chance. Classification of evidence: This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance.
Effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly: Secondary analysis of a randomized, double-blind, placebo-controlled trial
Rest, O. van de; Zwaluw, N.L. van der; Tieland, C.A.B. ; Adam, J.J. ; Hiddink, G.J. ; Loon, L.J.C. van; Groot, C.P.G.M. de - \ 2014
Mechanisms of Ageing and Development 136-137 (2014). - ISSN 0047-6374 - p. 85 - 93.
older-adults - alzheimers-disease - physical-activity - aerobic exercise - dietary-protein - performance - memory - strength - metaanalysis - impairment
Physical activity has been proposed as one of the most effective strategies to prevent cognitive decline. Protein supplementation may exert an additive effect. The effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly people was assessed in a secondary analysis. Two 24-week, double-blind, randomized, placebo-controlled intervention studies were carried out in parallel. Subjects performed a resistance-type exercise program of two sessions per week (n = 62) or no exercise program (n = 65). In both studies, subjects were randomly allocated to either a protein (2 × 15 g daily) or a placebo drink. Cognitive functioning was assessed with a neuropsychological test battery focusing on the cognitive domains episodic memory, attention and working memory, information processing speed, and executive functioning. In frail and pre-frail elderly, resistance-type exercise training in combination with protein supplementation improved information processing speed (changes in domain score 0.08 ± 0.51 versus -0.23 ± 0.19 in the non-exercise group, p = 0.04). Exercise training without protein supplementation was beneficial for attention and working memory (changes in domain scores 0.35 ± 0.70 versus -0.12 ± 0.69 in the non-exercise group, p = 0.02). There were no significant differences among the intervention groups on the other cognitive tests or domain scores.
Homocysteine, progression of ventricular enlargement, and cognitive decline. The Second Manifestations of ARTerial disease-Magnetic Resonance Study
Jochemsen, H.M. ; Kloppenborg, R.P. ; Groot, C.P.G.M. de; Kampman, E. ; Mali, W.P. ; Graaf, C. de; Geerlings, M.I. - \ 2013
Alzheimer's & Dementia 9 (2013)3. - ISSN 1552-5260 - p. 302 - 309.
brain atrophy - plasma homocysteine - risk-factor - folic-acid - probabilistic segmentation - elderly individuals - smart-mr - dementia - impairment - lesions
Background Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age. Methods Within the Second Manifestations of ARTerial disease-Magnetic Resonance study—a prospective cohort study among patients with atherosclerotic disease—longitudinal analyses were performed in 663 patients (mean age: 57 ± 9 years; follow-up: 3.9 ± 0.4 years). At baseline and follow-up, brain segmentation on magnetic resonance imaging was used to quantify relative (%) cortical, ventricular, and global brain volumes, and z-scores of memory and executive functioning were calculated. Linear regression analysis was used to estimate associations of homocysteine (per standard deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory, and executive functioning at follow-up, adjusted for baseline brain volume, memory, and executive functioning, respectively, and age, sex, and vascular risk factors. Furthermore, interaction terms between homocysteine and age (continuous) were added. Results Significant interactions were observed between total plasma homocysteine (tHcy) and age with cortical, ventricular, and global brain volume (for all three measures: P <.05), and between HHCY and age with executive functioning (P = .04), and results were stratified by age. In patients aged =65 years, increasing tHcy level and HHCY were significantly associated with progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]: 0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84, 95% CI: -1.37 to -0.32, respectively). Conclusion Elevated tHcy was related to progression of ventricular enlargement and increased the risk for a decline in executive functioning in older persons
Combined deficiency of iron and (n-3) fatty acids in male rates disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone
Baumgartner, J. ; Smuts, C.M. ; Malan, L. ; Arnold, M. ; Yee, B.K. ; Bianco, L.E. ; Boekschoten, M.V. ; Muller, M.R. ; Langhans, W. ; Hurrell, R.F. ; Zimmermann, M.B. - \ 2012
The Journal of Nutrition 142 (2012)8. - ISSN 0022-3166 - p. 1463 - 1471.
serotoninergic neurotransmission - working-memory - early-life - dopamine - oligodendrocytes - supplementation - myelination - impairment - expression - nutrition
Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21–56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70–76% and Fe by 20–32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P <0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID+(n-3)FAD rats. Furthermore, norepinephrine concentrations were increased 2-fold in the frontal cortex (FC) of (n-3)FAD rats (P <0.05). Dopa decarboxylase was downregulated in the hippocampus of ID and ID+(n-3)FAD rats (fold-change = -1.33; P <0.05). ID and (n-3)FAD significantly impaired working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P <0.05) and was negatively associated with 5-HT in FC (r = -0.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brain monoamine metabolism and produce greater deficits in reference memory than ID or (n-3)FAD alone.
|Gustatory and olfactory dysfunction in older adults: a national probability study
Boesveldt, S. ; Lindau, S.T. ; McClintock, M.K. ; Hummel, T. ; Lundstrom, J.N. - \ 2011
Rhinology 49 (2011)3. - ISSN 0300-0729 - p. 324 - 330.
odor identification - depressive symptoms - anorexia-nervosa - smell perception - united-states - taste - prevalence - disease - population - impairment
BACKGROUND: Olfactory and gustatory functions have not been well characterized in older adults in the US. Consequently, their relationships to sociodemographic characteristics, as well as physical and mental health, were studied in a large national probability sample using brief validated tests of chemosensory function. METHODS: A five-odour identification test and taste-impregnated strips of filter paper (sweet, sour, bitter, and salty) assessed the ability to identify chemosensory stimuli. RESULTS: Severe gustatory dysfunction was more prevalent than severe olfactory dysfunction. Age, education and sex were independently associated with performance on both the olfactory and gustatory identification tasks. Higher scores were associated with female sex, higher level of education, and lower age. Odour identification scores exhibited a positive, albeit weak, correlation with BMI, and food-related odours were better identified than non-food odours. In addition, odour identification performance was also negatively associated with depressive symptoms. CONCLUSIONS: These data demonstrate a high prevalence of severe gustatory and, to a somewhat lesser extent, olfactory dysfunction in a population-based sample and demonstrate that even brief tests are capable of detecting correlations between both chemical senses and relevant health measures outside a clinical setting.
Prevalence of smell loss in Parkinson's disease - A multicenter study
Haehner, A. ; Boesveldt, S. ; Berendse, H.W. ; Mackay-Sim, A. ; Fleischman, J. ; Silburn, P.A. ; Johnston, A.N. ; Mellick, G.D. ; Herting, B. ; Reichmann, H. ; Hummel, T. - \ 2009
Parkinsonism Related Disorder 15 (2009)7. - ISSN 1353-8020 - p. 490 - 494.
olfactory function - odor discrimination - identification - impairment - performance - dysfunction - diagnosis - disorder - hyposmia - criteria
Previous data on the prevalence of olfactory dysfunction in Parkinson's disease (PD) range from 45% to 90%. The present multicenter study aimed to provide data on the prevalence of smell loss in a large sample of PD patients from three independent populations. Olfactory sensitivity was tested in 400 patients from Australia, Germany, and The Netherlands by means of a psychophysical olfactory test, the "Sniffin' Sticks", which is comprised of 3 subtests of olfactory function. Out of the total number of patients 45.0% presented as functionally anosmic, 51.7% were hyposmic, whereas only 3.3% were normosmic. This indicates that 96.7% of PD patients present with significant olfactory loss when compared to young normosmic subjects. This figure falls to 74.5%, however, when adjusted to age-related norms. Thus, olfactory dysfunction should be considered as a reliable marker of the disease.
Decline in Cognitive Functioning Is Associated with a Higher Mortality Risk
Gelder, B.M. van; Tijhuis, M.A.R. ; Kalmijn, S. ; Giampaoli, S. ; Kromhout, D. - \ 2007
Neuroepidemiology 28 (2007)2. - ISSN 0251-5350 - p. 93 - 100.
mini-mental-state - alzheimers-disease - elderly-men - terminal decline - dementia - survival - population - death - netherlands - impairment
Objective: This study investigates the association between 5-year change in cognitive functioning and subsequent mortality. Methods:Four hundred and ninety-three Dutch and Italian men from the Finland, Italy, and the Netherlands Elderly (FINE) Study, born between 1900 and 1920, participated in the present study between 1990 and 2000. Cognitive functioning was measured with the Mini-Mental State Examination in 1990 and 1995, and mortality data were obtained until the year 2000. A proportional hazard analysis was used to investigate the association between 5-year change in cognitive functioning and subsequent 5-year mortality. Adjustments were made for age, education, country, lifestyle factors, prevalence of chronic diseases and, additionally, for baseline cognitive functioning. Results:Men whose cognition decreased (more than 1 standard deviation) between 1990 and 1995 had a 2-fold higher risk of dying in the following 5 years compared with men whose cognition was stable (adjusted hazard ratio = 1.9; 95% confidence interval 1.3-2.7). Mortality risk of men whose cognition improved between 1995 and 2000 was not different from men whose cognition was stable (adjusted hazard ratio = 1.1, 95% confidence interval 0.7-1.9). Conclusion:A decline in cognitive functioning is associated with a higher mortality risk.
Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamim B-12 deficiency: a randomized, placebo-controlled trial
Eussen, S.J. ; Groot, C.P.G.M. de; Joosten, L.W. ; Bloo, R. ; Clarke, R. ; Ueland, P.M. ; Schneede, J. ; Blom, H.J. ; Hoefnagels, W.H. ; Staveren, W.A. van - \ 2006
American Journal of Clinical Nutrition 84 (2006)2. - ISSN 0002-9165 - p. 361 - 370.
cobalamin deficiency - plasma homocysteine - methylmalonic acid - folate-deficiency - elderly people - impairment - supplementation - dementia - depression - serum
Background: Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. Objective: The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged 70 y with mild vitamin B-12 deficiency. Design: In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 µg vitamin B-12, 1000 µg vitamin B-12 + 400 µg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function. Results: Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains. Conclusion: Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function
Association of folate with hearing is dependent on the 5, 10-methylenetetrahydrofolate reductase 677C-->T mutation
Durga, J. ; Anteunis, L.J.C. ; Schouten, E.G. ; Bots, M.L. ; Kok, F.J. ; Verhoef, P. - \ 2006
Neurobiology of aging 27 (2006)3. - ISSN 0197-4580 - p. 482 - 489.
cardiovascular risk-factors - methylenetetrahydrofolate reductase - homocysteine concentrations - common mutation - disease - plasma - epidemiology - atherosclerosis - vitamin-b-12 - impairment
Vascular disease and its risk factors have been associated with the age-related hearing loss. We examined the association of elevated plasma homocysteine and its determinants with hearing levels. Pure-tone air conduction thresholds in 728 individuals with sensorineural hearing loss were not associated with homocysteine, erythrocyte folate and Vitamin B6. Low concentrations of serum folate and Vitamin B12 were associated with better hearing. When folate status was below the median, 5,10-methylenetetrahydrofolate reductase (MTHFR) 677TT homozygotes had similar hearing levels to subjects with a C allele. However, when folate status was above the median, MTHFR 677TT homozygotes had on an average 5 dB (p = 0.037) and 2.6 dB (p = 0.021) lower PTA-high and PTA-low hearing thresholds, respectively, than the subjects with a 677C allele. The relationship between serum folate and hearing thresholds appeared to be dependent on MTHFR 677 genotype (CC, r = 0.13, p = 0.034; TT, r = -0.10, p = 0.291). This supports the hypothesis that a greater one-carbon moiety commitment to de novo synthesis of nucleotides and an increase in formyl-folate derivatives relative to methyl-folate derivatives is protective for hearing.
Homocysteine and cognitive function in institutionalised elderly : a cross-sectional analysis
Manders, M. ; Vasse, E. ; Groot, C.P.G.M. de; Staveren, W.A. van; Bindels, J.G. ; Blom, H.J. ; Hoefnagels, W.H.L. - \ 2006
European Journal of Nutrition 45 (2006)2. - ISSN 1436-6207 - p. 70 - 78.
alzheimers-disease - plasma homocysteine - cardiovascular-disease - impairment - scale - vitamin-b-12 - performance - deficiency - people - folate
Several cross¿sectional, case¿control and prospective studies revealed a relation between homocysteine and cognitive function or dementia. These studies included either patient populations or healthy, community¿ dwelling elderly people. Aim of the study In this study we tested the hypothesis that homocysteine was inversely associated with cognitive function in a population of institutionalised elderly (aged ¿ 60 y; n = 157). For testing this hypothesis baseline data of a recently conducted intervention study in institutionalised elderly (median age 83 years) were used. Cognitive function was evaluated by the cognitive subscale of the Alzheimer's disease Assessment Scale (ADAS¿cog). The association between fasting plasma homocysteine level and cognitive function was investigated by multiple linear regression analysis. In the crude model homocysteine concentration was not significantly related to ADAS¿cog score (ß = 0.061; p = 0.45).Age was found to be related to ADAS¿cog score (ß = 0.161; p <0.05). Adjusting for age did however not result in a relation between homocysteine and cognitive function. In our study no association was found between homocysteine and cognitive function in a population of very old institutionalised subjects
Effect of an enriched drink on cognitive function in frail elderly persons
Wouters-Wesseling, W. ; Wagenaar, L. ; Rozendaal, M. ; Deijen, J.B. ; Groot, C.P.G.M. de; Bindels, J.G. ; Staveren, W.A. van - \ 2005
Journals of Gerontology. Series A: Biological Sciences & Medical Sciences 60 (2005)2. - ISSN 1079-5006 - p. 265 - 270.
mini-mental-state - nutritional-status - methylmalonic acid - plasma homocysteine - dietary-intake - b-vitamins - supplementation - performance - population - impairment
Many elderly persons report that they have difficulties learning new things and remembering names, plans, and conversations. Because decreased cognitive function in elderly persons is potentially related to their poor nutritional status, provision of essential nutrients may improve cognitive function. The authors wanted to determine whether consumption of an enriched drink, including moderate doses of all essential micronutrients, improves cognitive function in frail elderly persons. Methods. Frail, white adults (n = 101) who were aged 65 years or older with a body mass index ¿25 kg/m 2 were selected for this randomized, double-blind, placebo-controlled trial. They received either an enriched drink or a placebo product for 6 months. Before and after the intervention, participants' cognitive function was assessed (word learning test [WLT], WLT delayed, category fluency [CF] for animals and professions, and recognition memory test for words [RMTW]) and blood biochemical analyses (vitamin B12, homocysteine) were performed. Results. Sixty-seven residents completed the study period. After 6 months, significant differences were noted in changes of the WLT (0.9 ± 0.3 vs-0.1 ± 0.3; p = .014) and CF professions (1.2 ± 0.7 vs -0.6 ± 0.5; p = .017) in the supplement group (n = 34) compared with the placebo group (n = 33). No significant differences were observed in WLT delayed, RMTW, and CF animals. The plasma vitamin B12 concentration increased (105 ± 50 vs 8 ± 16; p = .003) and the homocysteine concentration decreased (-6.3 ± 5.9 vs -0.3 ± 2.9; p = .000) in the supplement group compared with the placebo group. Conclusions. This study contributes to the evidence that nutritional supplementation may improve neuropsychological performance in frail elderly persons.
Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression
Hensbroek, R.A. ; Kamal, A. ; Baars, A.M. ; Verhage, M. ; Spruijt, B.M. - \ 2003
Behavioural Brain Research 138 (2003)2. - ISSN 0166-4328 - p. 215 - 223.
cyclase mutant mice - synaptic plasticity - hippocampal-neurons - impairment - adult - ltp - neurogenesis - gene - stimulation - responses
The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is characterized by the absence of both mossy fiber long-term potentiation and long-term depression. This mutant was backcrossed to 129S3/SvImJ and C57Bl/6J to obtain standardized genetic backgrounds. Spatial working memory, assessed in the eight-arm radial maze, was unchanged in rab3A null-mutants. Moreover, one-trial cued and contextual fear conditioning was normal. Long-term spatial memory was tested in the Morris water maze. Two different versions of this task were used, an 'easy' version and a 'difficult' one. On both versions, no differences in search time and quadrant preferences were observed. Thus, despite the elimination of mossy fiber long-term plasticity, these tests revealed no impairments in mnemonic capabilities. We conclude that spatial, contextual and working memory do not depend on mossy fiber plasticity. (C) 2002 Published by Elsevier Science B.V.