Advanced glycation end-products are associated with the presence and severity of paratonia in early stage Alzheimer disease

Hans Drenth, Sytse U Zuidema, Wim P Krijnen, Ivan Bautmans, Cees van der Schans, Hans Hobbelen

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)636.e7-636.e12
JournalJournal of the American Medical Directors Association
Issue number7
Publication statusPublished - 2017


  • dementia
  • glycation
  • motor function


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