Hans Drenth

The Contribution of Advanced Glycation End product (AGE) accumulation to the decline in motor function

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 the ageing process.

Association between advanced glycation end-products and functional performance in Alzheimer's disease and mixed dementia

BACKGROUND People with Alzheimers 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 Alzheimers/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.

Advanced glycation end-products are associated with physical activity and physical functioning in the older population

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 were used. Linear regression analyses were utilized to study the associations between skin autofluorescence/AGE levels (AGE Reader), the number of physically active days (SQUASH), and physical functioning (RAND-36). A logistic regression analysis was used to study the 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% confidence interval: -0.35 to -0.07, p = .004), physical functioning (β = -1.60, 95% confidence interval: -2.64 to -0.54, p = .003), and compliance with the Dutch physical activity guidelines (odds ratio = 0.76, 95% confidence interval: 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.

Psychometric properties of the MyotonPRO in dementia patients with paratonia

Background: Paratonia is a distinctive form of hypertonia, causing loss of functional mobility in early stages of dementia to severe high muscle tone and pain in the late stages. For assessing and evaluating therapeutic interventions, objective instruments are required. Objective: Determine the psychometric properties of the MyotonPRO, a portable device that objectively measures muscle properties, in dementia patients with paratonia. Methods: Muscle properties were assessed with the MyotonPRO by 2 assessors within one session and repeated by the main researcher after 30 min and again after 6 months. Receiver operating characteristic curves were constructed for all MyotonPRO outcomes to discriminate between participants with (n = 70) and without paratonia (n = 82). In the participants with paratonia, correlation coefficients were established between the MyotonPRO outcomes and the Modified Ashworth Scale for paratonia (MAS-P) and muscle palpation. In participants with paratonia, reliability (intraclass correlation coefficient) and agreement values (standard error of measurement and minimal detectable change) were established. Longitudinal outcome from participants with paratonia throughout the study (n = 48) was used to establish the sensitivity for change (correlation coefficient) and responsiveness (minimal clinical important difference). Results: Included were 152 participants with dementia (mean [standard deviation] age of 83.5 [98.2]). The area under the curve ranged from 0.60 to 0.67 indicating the MyotonPRO is able to differentiate between participants with and without paratonia. The MyotonPRO explained 10-18% of the MAS-P score and 8-14% of the palpation score. Interclass correlation coefficients for interrater reliability ranged from 0.57 to 0.75 and from 0.54 to 0.71 for intrarater. The best agreement values were found for tone, elasticity, and stiffness. The change between baseline and 6 months in the MyotonPRO outcomes explained 8-13% of the change in the MAS-P scores. The minimal clinically important difference values were all smaller than the measurement error. Conclusion: The MyotonPRO is potentially applicable for cross-sectional studies between groups of paratonia patients and appears less suitable to measure intraindividual changes in paratonia. Because of the inherent variability in movement resistance in paratonia, the outcomes from the MyotonPRO should be interpreted with care; therefore, future research should focus on additional guidelines to increase the clinical interpretation and improving reproducibility.