Impaired motor function is a prominent characteristic of aging. Inflammatory processes and oxidative stress from advanced glycation end-products are related to impaired motor function and could plausibly be a contributing factor to the pathogenesis of paratonia, a specific motor disorder in people with dementia. Severe paratonia results in a substantial increase of a caretaker's burden and a decrease in the quality of life. The pathogenesis of paratonia is not well understood, and no effective interventions are available to combat it. Intensive glycaemic control, reducing oxidative stress, possibly combined with a low AGE diet and AGE targeting medication may be the key method for preventing advanced glycation end-product accumulation and reducing the inflammatory burden as well as possibly postponing or preventing paratonia.
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Diminishing motor function is commonly observed in the elderly population and is associated with a wide range of adverse health consequences. Advanced Glycation End products (AGE’s) may contribute to age-related decline in the function of cells and tissues in normal ageing. Although the negative effect of AGE’s on the biomechanical properties of musculoskeletal tissues and the central nervous system have been previously described, the evidence regarding the effect on motor function is fragmented, and a systematic review on this topic is lacking. Therefore, a systematic review was conducted from a total of eight studies describing AGE’s related to physical functioning, physical performance, and musculoskeletal outcome which reveals a positive association between high AGE’s levels and declined walking abilities, inferior ADL, decreased muscle properties (strength, power and mass) and increased physical frailty. Elevated AGE’s levels might be an indication to initiate (early) treatment such as dietary advice, muscle strengthening exercises, and functional training to maintain physical functions. Further longitudinal observational and controlled trial studies are necessary to investigate a causal relationship, and to what extent, high AGE’s levels are a contributing risk factor and potential biomarker for a decline in motor function as a component of ageing process.
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Paratonia, a distinctive form of hypertonia in patients with dementia, causes loss of functional mobility in early stage dementia to severe contractures and pain in the late stages. The pathogenesis of paratonia is not well understood. Patients in early stage dementia with diabetes mellitus showed a significantly higher risk for the development of paratonia. Both Alzheimer disease and diabetes mellitus are related to higher concentrations of advanced glycation end-products (AGEs). The purpose of this study is to explore the association of AGEs with the prevalence and severity of paratonia in patients with Alzheimer disease.DESIGN: Observational longitudinal, 1-year follow-up cohort study with 3 assessments.SETTING: Day care centers for patients with dementia.PARTICIPANTS: A total of 144 community-dwelling patients with early stage Alzheimer or Alzheimer/vascular disease were recruited from 24 dementia day care centers in The Netherlands.MEASUREMENTS: The presence of paratonia (Paratonia Assessment Instrument), the severity of paratonia (Modified Ashworth Scale for paratonia), and AGE levels (AGE-reader).RESULTS: From the 144 participants (56.3% female and 43.7% male, with a mean [standard deviation] age of 80.7 [7.7] years), 118 participants were available for final follow-up. A significant association between AGE levels and the presence of paratonia (odds ratio 3.47, 95% confidence interval [CI] 1.87-6.44, P < .001) and paratonia severity (β = 0.17, 95% CI 0.11-0.23, P < .001) was determined. In participants who developed paratonia and those with persistent paratonia throughout the study the AGE levels (95% CI -0.38 to -0.13, P < .001 and 95% CI -0.46 to -0.06, P = .012, respectively) and the severity of paratonia (95% CI -0.60 to -0.35, P < .001 and 95% CI -0.38 to -0.12, P < .001, respectively) significantly increased, whereas the AGE levels remained stable in those participants without paratonia. Notwithstanding, change in AGE levels was not significantly (P = .062) related to change in paratonia severity, mixed model analyses provided evidence for both a significant time and between participant effect of AGEs on paratonia severity.CONCLUSIONS: This study suggests that elevated AGE levels are a contributing factor to paratonia and its severity and could be the result of peripheral biomechanical changes reducing elasticity and increasing stiffness. These results provide a new perspective on paratonia and gives rise to further research whether paratonia could be postponed or movement stiffness can be improved by reducing AGE levels.
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From the article: "Scope: During food processing, the Maillard reaction ( М R) may occur, resulting in the formation of glycated proteins. Glycated proteins are of particular importance in food allergies because glycation may influence interactions with the immune system. This study compared native and extensively glycated milk allergen β -lactoglobulin (BLG), in their interactions with cells crucially involved in allergy. Methods and results: BLG was glycated in MR and characterized. Native and glycated BLG were tested in experiments of epithelial transport, uptake and degradation by DCs, T-cell cytokine responses, and basophil cell degranulation using ELISA and flow cytometry. Glycation of BLG induced partial unfolding and reduced its intestinal epithelial transfer over a Caco-2 monolayer. Uptake of glycated BLG by bone marrow–derived dendritic cells (BMDC) was increased, although both BLG forms entered BMDC via the same mechanism, receptor-mediated endocytosis. Once inside the BMDC, glycated BLG was degraded faster, which might have led to observed lower cytokine production in BMDC/CD4 + T-cells coculture. Finally, glycated BLG was less efficient in induction of degranulation of BLG-specific IgE sensitized basophil cells. Conclusions: This study suggests that glycation of BLG by MR significantly alters its fate in processes involved in immunogenicity and allergenicity, pointing out the importance of food processing in food allergy."
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BACKGROUND: People with Alzheimer's disease (AD) experience, in addition to the progressive loss of cognitive functions, a decline in functional performance such as mobility impairment and disability in activities of daily living (ADL). Functional decline in dementia is mainly linked to the progressive brain pathology. Peripheral biomechanical changes by advanced glycation end-products (AGEs) have been suggested but have yet to be thoroughly studied.METHODS: A multi-center, longitudinal, one-year follow-up cohort study was conducted in 144 people with early stage AD or mixed Alzheimer's/Vascular dementia. Linear mixed model analyses was used to study associations between AGE-levels (AGE reader) and mobility (Timed Up and Go), and ADL (Groningen Activity Restriction Scale and Barthel index), respectively.RESULTS: A significant association between AGE levels and mobility (β = 3.57, 95%CI: 1.43-5.73) was revealed; however, no significant association between AGE levels and ADL was found. Over a one-year time span, mean AGE levels significantly increased, and mobility and ADL performance decreased. Change in AGE levels was not significantly correlated with change in mobility.CONCLUSIONS: This study indicates that high AGE levels could be a contributing factor to impaired mobility but lacks evidence for an association with ADL decline in people with early stage AD or mixed dementia. Future research is necessary on the reduction of functional decline in dementia regarding the effectiveness of interventions such as physical activity programs and dietary advice possibly in combination with pharmacologic strategies targeting AGE accumulation.
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Background: Decline in physical activity and functioning is commonly observed in the older population and might be associated with biomarkers such as Advanced Glycation End-products (AGEs). AGEs contribute to age-related decline in the function of cells and tissues in normal aging and have been found to be associated with motor function decline. The aim of this study is to investigate the association between the levels of AGEs, as assessed by skin autofluorescence, and the amount of physical activity and loss of physical functioning in older participants.Methods: Cross-sectional data of 5,624 participants aged 65 years and older from the Lifelines cohort study was used. Linear regression analyses were utilized to study associations between skin autofluorescence/AGE-levels (AGE reader), the number of physically active days (SQUASH), and physical functioning (RAND-36), respectively. A logistic regression analysis was used to study associations between AGE-levels and the compliance with the Dutch physical activity guidelines (SQUASH).Results: A statistical significant association between AGE levels and the number of physically active days (β = -0.21, 95% CI: -0.35 to -0.07, P = .004), physical functioning (β = -1.60, 95% CI: -2.64 to -0.54, P = .003), and compliance with the Dutch physical activity guidelines (OR = 0.76, 95% CI: 0.62 to 0.94, P = .010) was revealed.Conclusions: This study indicates that high AGE levels may be a contributing factor as well as a biomarker for lower levels of physical activity and functioning in the older population.
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High consumption of carbohydrates is linked to metabolic syndrome, possibly via the endogenous formation of advanced glycated end-products. Many Dutch elementary school children have a carbohydrate intake of >130g/day, the estimated minimum requirement. In this observational study, 126 Dutch elementary school children (5-12y of age) from two schools differing in frequency of gym lessons (2 or 5 times a week) were included. In all participants, height, weight, waist circumference, autofluorescence of skin glycated end-products (AGE-score), sports activity and carbohydrate consumption were recorded once. Sports activities in leisure time differentiated participants in ‘sportsmen’ and ‘non-sportsmen’. Carbohydrate intake and AGE score were positively associated in non-sportsmen (p<0.003), but negatively in sportsmen (p<0.002). In sportsmen, but not in non-sportsmen (p>0.50), a positive association was found (p<0.002) between carbohydrate intake and subject age. The intake of total carbohydrate and carbohydrates from juices and soft drinks was lower (p<0.001) at the Wassenberg School relative to the Alexander School. Based on waist to height ratio, >95% of the children had normal fat mass. No correlations were found between waist to height ratio or BMI and carbohydrate intake. Waist to height ratio was positively associated with BMI (p<0.001)) and subject age (p<0.001). Of all principal parameters, AGE score is most affected by being sportsmen or not (p<0.001). This study indicates that an increased intake of carbohydrates can be counteracted by sufficient physical activity (>2.5 hours per week). This implies that skin autofluorescence is a fast and non-invasive method to screen children for life style.
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Physical activity has been proven to be effective in improving and sustaining physical and cognitive performance in dementia.
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Het lectoraat wil komen tot gezonde en veilige voedingsmiddelen voor doelgroepen die verschillen in voedingsbehoefte. Voeding is een ketenproduct. Verduurzaming van die keten is een tweede zwaartepunt. Een derde taak ligt in de netwerkfunctie en het steunen van regionale ontwikkelingen. Het lectoraat is actief in het toepassen van fundamentele kennis samen met het MKB. Anne Schaafsma is sinds 1978 in dienst bij FrieslandCampina en bekleedt sinds 2000 de functie van Senior Scientist Nutrition. Schaafsma is gespecialiseerd in kindervoeding en de invloed die het heeft op de ontwikkeling van hersenen en immuunsysteem. Als lector is Anne Schaafsma voor 2,5 dag per week bij Van Hall Larenstein in Leeuwarden gedetacheerd. Binnen het lectoraat werken de lector Food Safety (Anne Schaafsma) en associate lector Health & Food (Feike van der Leij) nauw samen. De lectoren willen fundamentele kennis benutten om te komen tot gezondere voedingsmiddelen voor doelgroepen die verschillen in leeftijd en voedingsbehoefte. Het betreft vooral kennis over moleculaire processen in het menselijk lichaam en de invloed van voedingscomponenten daarop.
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