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Biomechanical response of the CNS is associated with frailty in NPH-suspected patients


Frailty is known to predict dementia. However, its link with neurodegenerative alterations of the central nervous system (CNS) is not well understood at present. We investigated the association between the biomechanical response of the CNS and frailty in older adults suspected of normal pressure hydrocephalus (NPH) presenting with markers of multiple co-existing pathologies. The biomechanical response of the CNS was characterized by the CNS elastance coefficient inferred from phase contrast magnetic resonance imaging and intracranial pressure monitoring during a lumbar infusion test. Frailty was assessed with an index of health deficit accumulation. We found a significant association between the CNS elastance coefficient and frailty, with an effect size comparable to that between frailty and age, the latter being the strongest known risk factor for frailty. Results were independent of CSF dynamics, showing that they are not specific to the NPH neuropathological condition. The CNS biomechanical characterization may help to understand how frailty is related to neurodegeneration and detect the shift from normal to pathological brain ageing.

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This study was supported by a grant from the French Ministry of Health with the participation of the Groupement Interrégional de Recherche Clinique et d’Innovation Sud-Ouest Outre-Mer Hospitalier (PHRCInterRégional 2010), by research funding from the Occitania Region (RPBIO 2015 no 14054344), and by the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013)/ERC grant agreement no 615102 (https://erc.europa.eu/).

Author information

AV designed and conceptualized the study, processed, analysed and interpreted the data, performed the statistical analysis, and drafted and revised the manuscript. NDC and EH designed and conceptualized the study on the frailty part, interpreted the data, and drafted and revised the manuscript. AL segmented and analysed PCMRI data. OB provided tools and methods for PCMRI acquisition and data processing and analysed PCMRI data. ZC interpreted ICP measurements and revised the manuscript. LB and PP played a major role in the acquisition of clinical data and MRI data, respectively. PS designed and conceptualized the biomechanical part of the study, interpreted the data, and drafted and revised the manuscript. SL and ES designed and conceptualized the study, interpreted the data, drafted and revised the manuscript, supervised the study and obtained funding.

Correspondence to A. Vallet or E. Schmidt.

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Vallet, A., Del Campo, N., Hoogendijk, E.O. et al. Biomechanical response of the CNS is associated with frailty in NPH-suspected patients. J Neurol (2020). https://doi.org/10.1007/s00415-019-09689-z

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  • Biomechanics
  • Frailty
  • Normal pressure hydrocephalus
  • Lumbar infusion test
  • Phase contrast magnetic resonance imaging
  • Neurodegenerative CNS changes