Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Using bioconductor package BiGGR for metabolic flux estimation based on gene expression changes in brain
Gavai, A.K. ; Supandi, F. ; Hettling, H. ; Murrell, P. ; Leunissen, J.A.M. ; Beek, J.H.G.M. van - \ 2015
PLoS ONE 10 (2015)3. - ISSN 1932-6203 - 21 p.
alzheimers-disease - energy-metabolism - balance analysis - in-silico - models - glucose - biology - networks - neurons - oxygen
Predicting the distribution of metabolic fluxes in biochemical networks is of major interest in systems biology. Several databases provide metabolic reconstructions for different organisms. Software to analyze flux distributions exists, among others for the proprietary MATLAB environment. Given the large user community for the R computing environment, a simple implementation of flux analysis in R appears desirable and will facilitate easy interaction with computational tools to handle gene expression data. We extended the R software package BiGGR, an implementation of metabolic flux analysis in R. BiGGR makes use of public metabolic reconstruction databases, and contains the BiGG database and the reconstruction of human metabolism Recon2 as Systems Biology Markup Language (SBML) objects. Models can be assembled by querying the databases for pathways, genes or reactions of interest. Fluxes can then be estimated by maximization or minimization of an objective function using linear inverse modeling algorithms. Furthermore, BiGGR provides functionality to quantify the uncertainty in flux estimates by sampling the constrained multidimensional flux space. As a result, ensembles of possible flux configurations are constructed that agree with measured data within precision limits. BiGGR also features automatic visualization of selected parts of metabolic networks using hypergraphs, with hyperedge widths proportional to estimated flux values. BiGGR supports import and export of models encoded in SBML and is therefore interoperable with different modeling and analysis tools. As an application example, we calculated the flux distribution in healthy human brain using a model of central carbon metabolism. We introduce a new algorithm termed Least-squares with equalities and inequalities Flux Balance Analysis (Lsei-FBA) to predict flux changes from gene expression changes, for instance during disease. Our estimates of brain metabolic flux pattern with Lsei-FBA for Alzheimer’s disease agree with independent measurements of cerebral metabolism in patients. This second version of BiGGR is available from Bioconductor
Dietary patterns, cognitive decline, and dementia: a systematic review
Rest, O. van de; Berendsen, A.M. ; Haveman-Nies, A. ; Groot, C.P.G.M. de - \ 2015
Advances in Nutrition 6 (2015). - ISSN 2161-8313 - p. 154 - 168.
healthy eating index - mediterranean diet - alzheimers-disease - nutritional epidemiology - stop hypertension - physical-activity - randomized-trial - cluster-analysis - elderly-people - blood-pressure
Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline.
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.
Effects of homocysteine lowering with B vitamins on cognitive aging; meta-analysis of 11 trials with cognitive data on 22,000 individuals
Clarke, R. ; Bennett, D. ; Parish, S. ; Eussen, S.J.P.M. ; Groot, C.P.G.M. de - \ 2014
American Journal of Clinical Nutrition 100 (2014)2. - ISSN 0002-9165 - p. 657 - 666.
randomized controlled-trial - folic-acid supplementation - placebo-controlled trial - alzheimers-disease - older-adults - cardiovascular-disease - plasma homocysteine - stroke prevention - vascular-disease - double-blind
Background: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain. Objective: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging. Design: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340 individuals); Mini-Mental State Examination (MMSE)–type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals). Results: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean ± SE: -0.054 ± 0.004 and -0.036 ± 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domain trials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: -0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: -0.01; 95% CI: -0.03, 0.02). Overall, the effect of a 25% reduction in homocysteine equated to 0.02 y (95% CI: -0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment. Conclusion: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging.
Gene expression profiling of mesenteric lymph nodes from sheep with natural scrapie
Filali, H. ; Martin-Burriel, I. ; Harders, F. ; Varona, L. ; Hedman, C. ; Mediano, D.R. ; Monzón, M. ; Bossers, A. ; Badiola, J.J. - \ 2014
BMC Genomics 15 (2014). - ISSN 1471-2164 - 17 p.
carboxyl-terminal hydrolase - central-nervous-system - infected mouse brains - alzheimers-disease - prion protein - parkinsons-disease - identification - pathogenesis - tissues - prpsc
Background - Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease. Results - In the clinical stage of the disease, we detected 105 genes that were differentially expressed (=2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR. Conclusions - The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease.
No role for vitamin D or a moderate fat diet in aging induced cognitive decline and emotional reactivity in C57BL/6 mice
Brouwer, E.M. ; Schuurman, T. ; Groot, C.P.G.M. de; Feskens, E.J.M. ; Lute, C. ; Naninck, E.F.G. ; Arndt, S.S. ; Staay, F.J. van der; Bravenboer, N. ; Korosi, A. ; Steegenga, W.T. - \ 2014
Behavioural Brain Research 267 (2014). - ISSN 0166-4328 - p. 133 - 143.
serum 25-hydroxyvitamin d - d supplementation - d deficiency - depressive symptoms - alzheimers-disease - insulin-resistance - older women - pre-post - brain - association
Background Epidemiological studies have shown associations between vitamin D, mental health and glucose homeostasis in the elderly. Causal evidence, however, is still lacking. Objective The objective of this study was to investigate the importance of vitamin D in the prevention of emotional disturbances and cognitive decline in aging C57BL/6 mice, with pre-diabetes type II as potential effect modifier. Methods Mice were exposed to one of four diets from 10 months till 24 months of age: low fat vitamin D adequate (LFD), LF vitamin D deficient (LF), moderate fat vitamin D adequate (MFD), and MF vitamin D deficient (MF). The MFD/MF diet was applied to induce a condition resembling pre-diabetes type II. Behavior was assessed twice in the same group of mice at 6–8 and at 22–23 months of age using the Open Field Test (OFT), Elevated Plus Maze (EPM), Object Recognition Test (ORT) and the Morris Water Maze (MWM). Results We successfully induced vitamin D deficiency in the LF/MF mice. Moreover, fasting glucose and fasting insulin levels were significantly higher in MFD/MF mice than in LFD/LF mice. A significant aging effect was observed for most behavioral parameters. A MF(D) diet was shown to delay or prevent the age-related increase in emotional reactivity in the EPM. No effect of vitamin D or vitamin D*fat on behavioral outcomes was measured. Conclusion Aging significantly affected emotional reactivity and cognitive performance. Although other studies have shown effects of vitamin D on emotional reactivity and cognitive performance in mice, these findings could not be confirmed in aged C57BL/6 mice in this study.
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.
The impact of protein supplementation on cognitive performance in frail elderly
Zwaluw, N.L. van der; Rest, O. van de; Tieland, C.A.B. ; Adam, J.J. ; Hiddink, G.J. ; Loon, L.J.C. van; Groot, C.P.G.M. de - \ 2014
European Journal of Nutrition 53 (2014)3. - ISSN 1436-6207 - p. 803 - 812.
older-adults - alzheimers-disease - nutritional-status - dietary-protein - whey-protein - amino-acids - task-force - healthy - carbohydrate - decline
Purpose Maintenance of cognitive abilities is important for elderly to stay independent. With the aging of the population, the call for modifiable factors is emerging. Dietary protein might improve cognitive performance; however, this has hardly been studied. Therefore, we studied the impact of 24-week dietary protein supplementation on cognitive performance in pre-frail and frail elderly people. Methods Pre-frail and frail elderly subjects, according to the Fried criteria, randomly received a protein drink containing 15 g protein or a placebo drink twice a day. Cognitive performance was measured at baseline and after 24 weeks by means of a sensitive neuropsychological test battery. In addition, reaction time was assessed after both 12 and 24 weeks of intervention. Domain scores were calculated for the domains episodic memory, attention and working memory, information processing speed, and executive functioning. Analyses of covariance were used to determine differences between groups. Linear mixed models were used to determine differences in reaction time over time and per treatment. Results In total, 65 subjects (79 ± 8 years) with a median Mini-Mental State Examination score of 28 (interquartile range 26–30) were included. Reaction time improved more in the protein group (68 ms) than in the placebo group (18 ms, P = 0.03). Dietary protein had no significant effect on any of the cognitive domain scores. Conclusions Protein supplementation might improve reaction time performance in pre-frail and frail elderly, but did not improve other cognitive functions.
Total antioxidant capacity of the diet and major neurologic outcomes in older adults
Devore, E.E. ; Feskens, E.J.M. ; Ikram, M.A. ; Heijer, T. den; Vernooij, M. ; Lijn, F. van der; Hofman, A. ; Niessen, W.J. ; Breteler, M.M.B. - \ 2013
Neurology 80 (2013)10. - ISSN 0028-3878 - p. 904 - 910.
food-frequency questionnaire - alzheimers-disease - cardiovascular-disease - hippocampal atrophy - ischemic-stroke - rotterdam - risk - dementia - metaanalysis - association
Objective: To evaluate total antioxidant capacity of the diet, measured by the ferric-reducing antioxidant power (FRAP) assay, in relation to risks of dementia and stroke, as well as key structural brain volumes, in the elderly. Methods: We prospectively studied 5,395 participants in the Rotterdam Study, aged 55 years and older, who were dementia free and provided dietary information at study baseline; 5,285 individuals were also stroke free at baseline, and 462 were dementia and stroke free at the time of an MRI brain scan 5 years after baseline. Dietary data were ascertained using a semiquantitative food-frequency questionnaire, and combined with food-specific FRAP measurements from published tables; this information was aggregated across the diet to obtain “dietary FRAP scores.” Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of dementia and stroke, and multivariable-adjusted linear regression was used to estimate mean differences in structural brain volumes, across tertiles of dietary FRAP scores. Results: During a median 13.8 years of follow-up, we identified approximately 600 cases each of dementia and stroke. In multivariable-adjusted models, we observed no associations between dietary FRAP scores and risk of dementia (p trend = 0.3; relative risk = 1.12, 95% confidence interval = 0.91–1.38, comparing the highest vs lowest FRAP tertiles) or risk of stroke (p trend = 0.3; relative risk = 0.91, 95% confidence interval = 0.75–1.11, comparing extreme FRAP tertiles); results were similar across subtypes of these outcomes. Dietary FRAP scores were unrelated to brain tissue volumes as well. Conclusions: Total antioxidant capacity of the diet, measured by dietary FRAP scores, does not seem to predict risks of major neurologic diseases
Literature review on the role of dietary protein and amino acids in cognitive functioning and cognitive decline
Rest, O. van de; Zwaluw, N.L. van der; Groot, C.P.G.M. de - \ 2013
Amino Acids 45 (2013)5. - ISSN 0939-4451 - p. 1035 - 1045.
alpha-lactalbumin increases - nutritional-status - working-memory - l-tryptophan - alzheimers-disease - plasma tryptophan - elderly-people - sleep-deprivation - motor-performance - carbohydrate-rich
As the population of elderly people is growing rapidly, the number of individuals with dementia and cognitive impairment is also increasing. One of the preventive measures against cognitive decline is diet and different dietary factors have already been investigated. This review provides an overview of studies on dietary protein and cognitive functioning and cognitive decline. Also studies on the individual amino acids that are related to brain function, tryptophan and tyrosine, are discussed. Overall, the role of dietary protein intake on cognitive functioning as well as cognitive decline has hardly been studied; we found eight observational studies and three intervention studies. More studies investigated the role of tryptophan (14 studies) and tyrosine (nine studies) in relation to cognitive functioning, but all these studies were performed in young adult populations and mostly under special conditions. Research in elderly populations, in particular, is warranted. Also more research is needed to come to definitive conclusions and specific recommendations regarding protein intake or intake of specific amino acids for maintaining optimal cognitive functioning
B vitamins and n-3 fatty acids for brain development and function: review of human studies
Rest, O. van de; Hooijdonk, L.W.A. ; Doets, E.L. ; Schiepers, O.J.G. ; Eilander, J.H.C. ; Groot, C.P.G.M. de - \ 2012
Annals of Nutrition & Metabolism 60 (2012)4. - ISSN 0250-6807 - p. 272 - 292.
alpha-linolenic acid - long-chain omega-3-fatty-acids - randomized controlled-trials - quality-of-life - depressive symptoms - docosahexaenoic acid - alzheimers-disease - folic-acid - cognitive function - fish consumption
Background: Nutrition is one of many factors that affect brain development and functioning, and in recent years the role of certain nutrients has been investigated. B vitamins and n–3 polyunsaturated fatty acids (PUFA) are two of the most promising and widely studied nutritional factors. Methods: In this review, we provide an overview of human studies published before August 2011 on how vitamin B6, folate, vitamin B12 and n–3 PUFA may affect the brain, their nutrient status and the existing evidence for an association between these nutrients and brain development, brain functioning and depression during different stages of the life cycle. Results: No recommendation can be given regarding a role of B vitamins, either because the number of studies on B vitamins is too limited (pregnant and lactating women and children) or the studies are not consistent (adults and elderly). For n–3 PUFA, observational evidence may be suggestive of a beneficial effect; however, this has not yet been sufficiently replicated in randomized controlled trials (RCTs). Conclusions: We found that the existing evidence from observational studies as well as RCTs is generally too limited and contradictory to draw firm conclusions. More research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs
Dietary protein intake in community-dwelling, frail, and institutionalized elderly people: scope for improvement
Tieland, C.A.B. ; Borgonjen-van den Berg, K.J. ; Loon, L.C. van; Groot, C.P.G.M. de - \ 2012
European Journal of Nutrition 51 (2012)2. - ISSN 1436-6207 - p. 173 - 179.
randomized controlled-trial - physical-activity scale - doubly labeled water - alzheimers-disease - body-composition - skeletal-muscle - older-people - amino-acids - lean mass - exercise
Adequate dietary protein intake is required to postpone and treat sarcopenia in elderly people. Insight into dietary protein intake in this heterogeneous population segment is needed to locate dietary inadequacies and to identify target populations and feeding strategies for dietary interventions. Therefore, we assessed dietary protein intake, distribution of protein intake throughout the day, and the use of protein-containing food sources in community- dwelling, frail, and institutionalized elderly people in the Netherlands. Methods Secondary analyses were carried out using dietary data collected from studies among community-dwelling, frail, and institutionalized elderly people to evaluate protein intake characteristics. Results Dietary protein intake averaged 1.1 ± 0.3 g/kgbw/ day in community-dwelling, 1.0 ± 0.3 g/kg-bw/day in frail, and 0.8 ± 0.3 g/kg-bw/day in institutionalized elderly men. Similar protein intakes were found in women. Ten percent of the community-dwelling and frail elderly and 35% of the institutionalized elderly people showed a protein intake below the estimated average requirement (0.7 g/kg-bw/day). Protein intake was particularly low at breakfast in community-dwelling (10 ± 10 g), frail (8 ± 5 g), and institutionalized elderly people (12 ± 6 g) with bread and dairy products as predominant protein sources. Conclusions Whereas daily protein intake is generally well above the recommended dietary allowance in community- dwelling and frail elderly people, a significant proportion of institutionalized elderly showed an intake below the current protein requirement, making them an important target population for dietary interventions. Particularly at breakfast, there is scope for improving protein intake.
Genetic variation in folate metabolism is not associated with cognitive functioning or mood in healthy adults
Schiepers, O.J.G. ; Boxtel, M.P.J. van; Groot, R.H.M. ; Jolles, J. ; Bekers, O. ; Kok, F.J. ; Verhoef, P. ; Durga, J. - \ 2011
Progress in Neuro-Psychopharmacology and Biological Psychiatry 35 (2011)7. - ISSN 0278-5846 - p. 1682 - 1688.
methylenetetrahydrofolate reductase gene - serine hydroxymethyltransferase genes - mthfr c677t polymorphism - participants aged 24-81 - normative data - thymidylate synthase - alzheimers-disease - colorectal-cancer - common mutation - depression
The present study examined the associations between genetic variation in folate metabolism on the one hand and cognitive functioning and mood on the other in healthy individuals. Two independent population-based samples were used, including 777 participants, aged 24-82 years, from the Maastricht Aging Study (MAAS): and 818 participants, aged 50-70 years, from the Folic Acid and Carotid Intima-Media Thickness (FACIT) study. Thymidylate synthase (75.) 2R -> 3R and serine hydroxymethyltransferase (SHMT1) 1420C -> J polymorphisms were determined in both populations. In addition, the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C -> T polymorphism was determined in the MAAS population. Cognitive performance was assessed in both populations using a neuropsychological test battery. In the MAAS population only, cognitive performance was retested after 12 years of follow-up (n = 612), and mood was measured at baseline (n = 772) and 12-year follow-up (n = 565) by means of the depression subscale of the Symptom Checklist 90. We found that in both study populations, cognitive performance was not associated with TS 2R -> 3R or SHMT1 1420C -> T polymorphisms at baseline, after correction for age, sex, and level of education. The MTHFR 677C -> T polymorphism was not associated with cognitive performance in the MAAS population. None of the polymorphisms in the MAAS population were related to mood at baseline or over 12 years. In conclusion, our findings do not support the involvement of genetic variation in folate metabolism in cognitive performance or mood in healthy individuals.
Gene expression profiling en association with prion-related lesions in the medulla oblongata of symptomatic natural scrapie animals.
Filali, H. ; Martin-Burriel, I. ; Harders, F. ; Varona, L. ; Lyahyai, J. ; Zaragoza, P. ; Pumarola, M. ; Badiola, J.J. ; Bossers, A. ; Bolea, R. - \ 2011
PLoS ONE 6 (2011)5. - ISSN 1932-6203 - 12 p.
bovine spongiform encephalopathy - creutzfeldt-jakob-disease - pancreatitis-associated protein - central-nervous-system - human substantia-nigra - infected mouse brains - alzheimers-disease - parkinsons-disease - messenger-rna - glutathione-peroxidase
The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed.
Pharma-nutrition interface: The gap is narrowing
Georgiou, N.A. ; Garssen, J. ; Witkamp, R.F. - \ 2011
European Journal of Pharmacology 651 (2011)1-3. - ISSN 0014-2999 - p. 1 - 8.
regulatory t-cells - obstructive pulmonary-disease - inflammatory-bowel-disease - cancer cachexia - metabolic syndrome - alzheimers-disease - insulin-resistance - obesity - infection - probiotics
The interaction between pharmacology and nutrition science is on the rise. Nutritional status is considered one of the important determinants of health and disease and several diseases of our time have a clear link with lifestyle factors including the diet. There is also increasing realization that a continuum between health and disease often exists without strict boundaries. Understanding the subtle interactions between genes, environment and homeostatic processes is the key in finding effective ways to prevent, treat or manage disease. Both pharmacologists and nutritionists are recognizing that most of the low hanging fruit has been picked, and that the one disease–one target–one drug (or nutrient) concept will provide fewer successes than it did in the past. Instead, complex multi-factorial diseases require multi-pathway understanding and multi-targeting approaches which will often result in compound combinations. Therapeutic synergy between foods and drugs does not necessarily mean that both have the same primary target. There are also examples of nutritional products that effectively contribute to the therapeutic regimen by improving the patients' general condition or by reducing side-effects of drugs. Examples of conditions and diseases that are highlighted in this review include the metabolic syndrome with its co-morbidities, immune-related diseases and HIV. With the aging population there are other fields emerging, including CNS-related diseases and cancer, where we will likely see an increased synergy between the two disciplines that seemed to have lost contact since the times of Hippocrates
Serum Iron Parameters, HFE C282Y Genotype, and Cognitive Performance in Older Adults: Results From the FACIT Study
Schiepers, O.J.G. ; Boxtel, M.P.J. van; Groot, R.H.M. ; Jolles, J. ; Kort, W.L.A.M. de; Swinkels, D.W. ; Kok, F.J. ; Verhoef, P. ; Durga, J. - \ 2010
Journals of Gerontology. Series A: Biological Sciences & Medical Sciences 65 (2010)12. - ISSN 1079-5006 - p. 1312 - 1321.
transferrin-bound iron - participants aged 24-81 - restless legs syndrome - normative data - alzheimers-disease - gene-mutations - neurodegenerative disorders - hereditary hemochromatosis - parkinsons-disease - physical-activity
Although iron homeostasis is essential for brain functioning, the effects of iron levels on cognitive performance in older individuals have scarcely been investigated. In the present study, serum iron parameters and hemochromatosis (HFE) C282Y genotype were determined in 818 older individuals who participated in a 3-year randomized, placebo-controlled double-blind trial examining the effects of folic acid on carotid intima-media thickness. All participants had slightly elevated homocysteine levels and were vitamin B12 replete. Cognitive functioning was assessed at baseline and after 3 years by means of a neuropsychological test battery. At baseline, increased serum ferritin was associated with decreased sensorimotor speed, complex speed, and information-processing speed and increased serum iron was associated with decreased sensorimotor speed. Cognitive performance over 3 years was not associated with HFE C282Y genotype or iron parameters. In conclusion, serum iron parameters do not show a straightforward relationship with cognitive functioning, although elevated iron levels may decrease cognitive speed in older individuals susceptible to cognitive impairment.
Advanced time-series analysis of MEG data as a method to explore olfactory function in healthy controls and Parikinson's disease patients
Boesveldt, S. ; Knol, D.L. ; Verbunt, J.P.A. ; Berendse, H.W. - \ 2009
Human Brain Mapping 30 (2009)9. - ISSN 1065-9471 - p. 3020 - 3030.
oscillatory brain activity - working-memory - synchronization likelihood - alzheimers-disease - eeg alpha - stimulation - odor - connectivity - dysfunction - band
Objectives: To determine whether time-series analysis of magnetoencephalography (MEG) data is a suitable method to study brain activity related to olfactory information processing, and to detect differences in odor-induced brain activity between patients with Parkinson's disease (PD) and controls. Methods: Whole head 151-channel MEG recordings were obtained in 21 controls and 20 patients with PD during a 10-min olfactory stimulus paradigm, consisting of 10 alternating rest-stimulus cycles (30 s each), using phenylethyl alcohol administered by means of a Burghart olfactometer. Relative spectral power and synchronization likelihood (SL; an unbiased measure of functional connectivity) were calculated for delta, theta, alpha1, alpha2, beta, and gamma frequency bands. Results: In controls, olfactory stimulation produced an increase in theta power and a decrease in beta power. In patients with PD, there was a decrease in alpha1 power. No significant interaction between group and condition was found for spectral power. SL analysis revealed a significantly different response to olfactory stimulation in patients with PD compared to controls. In controls, the odor stimulus induced a decrease in local beta band SL. The response in patients with PD involved a decrease in intrahemispheric alpha2 band SL. Conclusion: This is the first study to show that time-series analysis of MEG data, including spectral power and SL, can be used to detect odor-induced changes in brain activity. In addition, differences in odor-induced brain activity were found between patients with PD and controls using analysis of SL, but not of spectral power
Odor recognition memory is not idepentently impaired in Parkinson's disease
Boesveldt, S. ; Muinck Keizer, R.J.O. de; Wolters, E.C.H. ; Berendse, H.W. - \ 2009
Journal of Neural Transmission 116 (2009)5. - ISSN 0300-9564 - p. 575 - 578.
alzheimers-disease - olfactory function - identification ability - sniffin sticks - diagnosis - tests - sign
The results of previous studies in small groups of Parkinson's disease (PD) patients are inconclusive with regard to the presence of an odor recognition memory impairment in PD. The aim of the present study was to investigate odor recognition memory in PD in a larger group of patients. Odor recognition memory and detection thresholds were assessed using components of the "Sniffin' Sticks" test battery in 55 non-demented PD patients (Hoehn and Yahr stages I-III) and 50 control subjects of comparable age and sex. PD patients performed slightly but significantly worse than control subjects on the odor recognition memory task. After correction for odor detection scores, however, the difference in odor recognition memory performance between PD patients and controls was no longer statistically significant. These data indicate that odor recognition memory is not independently impaired in PD patients
Methodological Issues in Primary Prevention Trials for Neurodegenerative Dementia
Andrieu, S. ; Coley, N. ; Aisen, P. ; Carrillo, M.C. ; DeKosky, S. ; Durga, J. ; Fillit, H. ; Frisoni, G.B. ; Froelich, L. ; Gauthier, S. ; Jones, R. ; Jonsson, L. ; Khachaturian, Z. ; Morris, J.C. ; Orgogozo, J.M. ; Ousset, P.J. ; Robert, P. ; Salmon, E. ; Sampaio, C. ; Verhey, F. ; Wilcock, G. ; Vellas, B. - \ 2009
Journal of Alzheimers Disease 16 (2009)2. - ISSN 1387-2877 - p. 235 - 270.
mild cognitive impairment - randomized controlled-trial - placebo-controlled trial - health initiative memory - quality-of-life - mrc/bhf heart protection - population-based cohort - vascular risk-factors - mini-mental state - alzheimers-disease
The prevention of neurodegenerative dementias, such as Alzheimer's disease, is a public health priority. Due to the large numbers of affected patients, even interventions bringing about a relatively small delay in disease onset could have large public health effects. Randomized controlled trials (RCTs) are required to demonstrate the effectiveness of preventive interventions, but such trials raise specific methodological questions because they are new in the field of neurodegenerative diseases, and require large numbers of elderly subjects and lengthy follow-up periods. We performed a literature search to identify primary prevention RCTs for neurodegenerative dementia. The methodology of the trials was summarized and discussed during two expert meetings. Overall, 39 trials were identified that assessed dementia incidence or cognitive decline as a primary or secondary study outcome. Age was the most common selection criteria for target populations. Follow-up periods ranged from one month to nine years and were longest in studies measuring dementia incidence as an outcome. Results of RCTs have so far been generally negative and conflicting with those of observational studies, perhaps due to methodological issues. Future trials must therefore carefully consider the target population, outcomes and duration of follow-up to be used, and should assess the problem of attrition.
The effect of a nutrient dense drink on mental and physical function in institutionalized elderly people
Manders, M. ; Groot, C.P.G.M. de; Hoefnagels, W.H.L. ; Dhonukshe-Rutten, R.A.M. ; Wouters-Wesseling, W. ; Mulders, A.J.M.J. ; Staveren, W.A. van - \ 2009
Journal of Nutrition, Health and Aging 13 (2009)9. - ISSN 1279-7707 - p. 760 - 767.
liquid nutrition supplement - nursing-home residents - alzheimers-disease - cognitive performance - methylmalonic acid - controlled-trial - scale - risk - homocysteine - exercise
Objectives To determine whether in the current study the supply of a nutrient dense drink has a positive effect on mental and physical function of institutionalized elderly people. Design A 24-week, randomized, double-blind, placebo-controlled, parallel-group, intervention trial. Setting Homes for the elderly and nursing homes in the Netherlands. Participants Institutionalized elderly people older than 60 years, with a BMI = 30 kg/m2, and a Mini-Mental State Examination score of at least 10 points. Intervention In addition to their usual diet the participants (n=176) received either a nutrient dense drink or a placebo drink twice a day during 24 weeks. Measurements The functionality measures included cognitive function, mood, physical performance and the ability to perform activities of daily living. Results In the supplement group a favorable effect of the intervention drink on body weight (1.6 kg difference in change; P =.035), calf circumference (0.9 cm difference in change; P =.048), and blood values (e.g. Hcy decreased from 16.8 to 11.2 µmol/L in the supplement group) was found. In the total group no significant effect was found on functionality outcomes. However, a subgroup of participants with BMI at baseline below 24.4 kg/m2 performed better on the cognitive subscale of Alzheimer’s Disease Assessment Scale (P =.09), and its language sub score (P =.01) after 24 weeks of intervention. Conclusion The results in the total group of this trial suggest that the nutritional supplement used in this study improves nutritional status. Furthermore, the results of this trial suggest that it is effective as treatment for decreasing function in a subgroup of institutionalized elderly people with low BMI.
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