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.
BACKGROUND: Paratonia is a progressive motor problem that is observed in individuals with dementia and is not a well-known phenomenon. This study explores the development and risk factors of paratonia in moderate stage dementia patients.METHODS: A multi-center, longitudinal, one-year follow-up cohort study was performed. Patients with an established diagnosis of dementia, with a score of 6 or lower on the Global Deterioration Scale (GDS) were included. The participants were assessed using the Paratonia Assessment Instrument (PAI), the Timed Up and GO test, the Qualidem, the Global Deterioration Scale (Reisberg et al., 1982) and the Mini-mental State Examination. Information about each patient's diagnosis of dementia, comorbidities and use of medication were obtained from the participant's medical file. The PAI was assessed every three months, the other variables at baseline and after 12 months. Cross-tabulation χ2 and logistic regression tests were used for the statistical analyses.RESULTS: Baseline measures were assessed in the 204 participants - 111 (54%) female and 93 (46%) male, with a mean age of 79.8 years (56-97). Seventy-one patients (34.8%) were diagnosed with paratonia at baseline, and 51 patients developed paratonia over one year. The highest hazard ratio (3.1) for developing paratonia within one year was observed in the vascular dementia group. The logistic regression analysis revealed that the presence of diabetes mellitus (OR = 10.7) was significantly related to the development of paratonia (Wald χ2 p-value < 0.01).CONCLUSIONS: Diabetes mellitus and likely vascular damage are risk factors for the development of paratonia.
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.
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.
