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

Abstract

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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Advanced Glycosylation End Products
Alzheimer Disease
Confidence Intervals
Dementia
Day Care
Diabetes Mellitus
Elasticity
Contracture
Vascular Diseases
Netherlands
Cohort Studies
Odds Ratio
Pain

Keywords

  • dementia
  • glycation
  • motor function

Cite this

@article{d3db8598e37a446ab7bbc48458f428ac,
title = "Advanced glycation end-products are associated with the presence and severity of paratonia in early stage Alzheimer disease",
keywords = "dementia, glycation, motor function, dementie, glycatie, motoriek",
author = "Hans Drenth and Zuidema, {Sytse U} and Krijnen, {Wim P} and Ivan Bautmans and {van der Schans}, Cees and Hans Hobbelen",
note = "Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.",
year = "2017",
doi = "10.1016/j.jamda.2017.04.004",
journal = "Journal of the American Medical Directors Association",
issn = "1525-8610",
publisher = "Elsevier",

}

TY - JOUR

T1 - Advanced glycation end-products are associated with the presence and severity of paratonia in early stage Alzheimer disease

AU - Drenth,Hans

AU - Zuidema,Sytse U

AU - Krijnen,Wim P

AU - Bautmans,Ivan

AU - van der Schans,Cees

AU - Hobbelen,Hans

N1 - Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - dementia

KW - glycation

KW - motor function

KW - dementie

KW - glycatie

KW - motoriek

U2 - 10.1016/j.jamda.2017.04.004

DO - 10.1016/j.jamda.2017.04.004

M3 - Article

JO - Journal of the American Medical Directors Association

T2 - Journal of the American Medical Directors Association

JF - Journal of the American Medical Directors Association

SN - 1525-8610

ER -