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.
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.
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.
De samenwerking tussen de onderzoeksgroep FRIA van de Vrije Universiteit Brussel, afdeling oudergeneeskunde van het UMCG Groningen en de onderzoeksgroep (lectoraat) Healthy Ageing, Allied health Care and Nursing van de Hanzehogeschool Groningen is gericht op onderzoek naar bewegingsstoornissen bij veroudering. In het bijzonder wordt gekeken naar paratonic, een bewegingsstoornis bij dementie.The International Joint Research group ‘Move in Age’ concluded in a systematic review that paratonia still is a barely understood and devastating phenomenon in dementia and revealed the urgency of gaining more insight in the pathophysiology. Paratonia, a distinctive change in muscle tone, starts in early stages of dementia and develops further with progress of the disease. Resulting in severe discomfort for patients, but also affecting caregivers since daily care becomes increasingly difficult. It is hypothesized that changes in motor control due to dementia influences peripheral neurological control and biomechanical muscle structures (by crosslinking and inflammation caused by advanced glycation end-products (AGEs).This IJRG started in 2018 and aims to develop a long-term comprehensive research program on movement-related impairments at higher age. The three partners have a strong track record on research in the area of movement-related impairments in older persons; however, each focusing on a specific aspect. In fact, the Frailty in Ageing research group (FRIA) of the Vrije Universiteit Brussel (VUB) is running focused research program on the triad sarcopenia-dynapenia-inflammation with mainly a bio-gerontological and bio-psycho-medical approach; the department of General Practice and Elderly Care Medicine of the University Medical Center Groningen (UMCG) has anongoing research line on the medical aspects of mobility impairments in frail elderly persons and in elderly dementia patients; and finally Research Group Healthy Ageing, Allied Health Care and Nursing of the Hanze University of Applied Sciences Groningen (HUAS) developed a research program on physical, psycho-cognitive and social dimensions of frailty including the functional impact of mobility impairments. In the first 3-5 years, the focus will be on the movement-related impairments that occur in patients with dementia and in specific on paranoia. The programme will be extended towards movement-related impairments in the context of other geriatric syndromes.