Gait Decline

HomeHypertensionVol. 66, No. 2Gait Decline Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBGait DeclineThe Role of Cerebral Small Vessel Disease and Biomarkers Julien Dumurgier and Alexis Elbaz Julien DumurgierJulien Dumurgier From the Memory Center of Lariboisiere Hospital, CMRR Paris Nord, Saint Louis—Lariboisiere—Fernand Widal Hospital, AP-HP, Paris, France (J.D.); INSERM U942, Biomarkers and Neurocognition, University Paris 7-Denis Diderot, Paris, France (J.D.); INSERM, Centre for Research in Epidemiology and Population Health, U1018, Epidemiology of Ageing and Age Related Diseases, Villejuif, France (A.E.); and Université Paris-Sud 11, UMR-S 1018, Villejuif, France (A.E.). and Alexis ElbazAlexis Elbaz From the Memory Center of Lariboisiere Hospital, CMRR Paris Nord, Saint Louis—Lariboisiere—Fernand Widal Hospital, AP-HP, Paris, France (J.D.); INSERM U942, Biomarkers and Neurocognition, University Paris 7-Denis Diderot, Paris, France (J.D.); INSERM, Centre for Research in Epidemiology and Population Health, U1018, Epidemiology of Ageing and Age Related Diseases, Villejuif, France (A.E.); and Université Paris-Sud 11, UMR-S 1018, Villejuif, France (A.E.). Originally published8 Jun 2015https://doi.org/10.1161/HYPERTENSIONAHA.115.05437Hypertension. 2015;66:263–264Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2015: Previous Version 1 See related article, pp 340–346With the global increasing aging of our societies, there is a growing interest in understanding the mechanisms explaining mobility limitations and poor physical performance in elderly population. Epidemiological studies report that, in community-dwelling older adults, the prevalence of abnormal gait could be >30% after the age of 70 years.1 One of the most obvious complications of poor physical performance is an increased risk of falls, which may have tragic consequences. After an hip fracture, for example, the 1-year risk of mortality is ≈30%,2 higher than after an acute myocardial infarction. Overall, poor physical performance is associated with an increased risk of disability, institutionalization, and death.3 The simple measurement of short-distance usual gait speed (usually over a distance of 4–10 m) has progressively emerged as a simple and reliable measure of physical performance, requiring only a chronometer and a few seconds, leading some authors to propose it as a new vital sign in the geriatric examination, together with other parameters, such as blood pressure or heart rate.4The causes of mobility limitations are complex and multifactorial, involving many systems such as osteoarticular or cardiovascular systems, sensorial abilities, or the central nervous system.5 A growing number of studies have focussed on the role of cardiovascular risk factors, by analogy with cognitive function. Dyslipidemia, diabetes mellitus, and hypertension have all been shown to be associated with poor physical performance.6 Slow gait speed is associated with cardiovascular risk,7 and with an increased risk of stroke and cardiovascular mortality.8 One of the explanations for the association between cardiovascular risk factors and poor physical performance involves the role of cerebral small vessel disease, that is, brain white matter abnormalities,9 silent infarcts, and gray matter atrophy.10 Cardiovascular risk factors are associated with cerebral small vessel disease, which impairs brain connectivity and the pathways controlling cognition, balance, and motor function. These associations may reinforce themselves in a vicious circle, as mobility limitations may generate sedentary behavior, thereby promoting cardiovascular risk factors (Figure).Download figureDownload PowerPointFigure. Relationship between cardiovascular risk factors and mobility limitations in elderly people.In this issue of Hypertension, Tchalla et al11 have examined the association between plasma levels of Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1)—a biomarker of systemic endothelial dysfunction—and mobility impairment, assessed through a gait speed measure and the occurrence of falls >1 year. sVCAM-1 promotes the adhesion of inflammatory cells to the vascular endothelial wall, in particular in the cerebral microvasculature, and facilitates their migration through the endothelium.12 According to the authors, the resulting inflammatory response may result in impaired cerebral blood flow regulation, especially endothelium-dependent vasodilatation in response to changes in blood end-tidal Pco2, and ischemic damage to the cerebral microvasculature that manifests as white matter hyperintensities in brain imaging studies. In this work, ≈700 community-dwelling participants aged ≥65 years were included as part of the MOBILIZE (Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly) Boston Study. The authors found that elevated levels of sVCAM-1 were cross-sectionnally associated with slower gait speed, and with an increased risk of incident falls, including injurious falls, over the 1-year follow-up. Furthermore, a transcranial Doppler ultrasound was available for 60% of the participants: sVCAM-1 levels were associated with decreased resting blood flow velocity and cerebral vasomotor range, therefore, suggesting, according to the authors, that plasma sVCAM-1 is a marker of chronic cerebral blood flow dysregulation secondary to endothelial dysfunction.Critics will dispute the specificity of sVCAM-1 as a marker of cerebral blood flow dysregulation and regret the absence of brain magnetic resonance imaging to assess the presence of cerebral small vessel disease. The reader is also left with the question of whether hypertension and slow gait speed were associated in this population, and, if yes, whether s-VCAM1 explained part of the association. In addition, the association between sVCAM-1 and slow gait speed was characterized by a complex pattern: higher sVCAM-1 levels were associated with slow gait speed only among participants with a history of controlled or uncontrolled hypertension (79% of all participants), while there was no association among normotensive subjects. Additional studies will be necessary to replicate this finding and better understand the mechanisms underlying this interaction. The authors also claim that they used a longitudinal design to examine the association of sVCAM-1 with incident falls. However, the follow-up was short (1 year), and, more importantly, participants with a history of falls were not excluded from this analysis; therefore, their findings may be explained by those participants who walked slowly and had already fallen at the time of the sVCAM-1 measure.Nevertheless, sVCAM-1 may rejoin the previous list of plasma inflammatory biomarkers, such as interleukin 6, which have shown to be associated with both cardiovascular risk and mobility limitations in elderly people.13 The availibility of 1 or several plasma biomarkers associated with the vascular component of mobility limitations presents a large interest, as they may contribute to identify subjects who may benefit from targeted interventions.Mobility limitations in elderly people represent a major challenge for public health. The findings of Tchalla et al11 add to an increasing literature that pleads for a contribution of vascular risk factors to mobility impairment and offers an opportunity for prevention. Whether vascular drugs, such as antihypertensive drugs or statins,14 could have a protective effect for mobility in elderly people needs to be tested in randomized clinical trials. Repeated measures of gait speed and plasma biomarkers will be particularly valuable in the design of such studies.Sources of FundingDr Dumurgier was supported by the Philippe Foundation and the Institut Servier. Dr Elbaz was supported by Agence Nationale de la Recherche, Agence Nationale de Sécurité du Médicament, Institut de Recherche en Santé Publique.DisclosuresNone.FootnotesThe opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.Correspondence to Julien Dumurgier, Memory Center, Lariboisiere Hospital, 200 rue du Faubourg Saint-Denis, 7510 Paris, France. E-mail [email protected]References1. Verghese J, LeValley A, Hall CB, Katz MJ, Ambrose AF, Lipton RB.Epidemiology of gait disorders in community-residing older adults.J Am Geriatr Soc. 2006; 54:255–261. doi: 10.1111/j.1532-5415.2005.00580.x.CrossrefMedlineGoogle Scholar2. Parker M, Johansen A.Hip fracture.BMJ. 2006; 333:27–30. doi: 10.1136/bmj.333.7557.27.CrossrefMedlineGoogle Scholar3. Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults.JAMA. 2011; 305:50–58. doi: 10.1001/jama.2010.1923.CrossrefMedlineGoogle Scholar4. Hall WJ.Update in geriatrics.Ann Intern Med. 2006; 145:538–543.CrossrefMedlineGoogle Scholar5. Rosso AL, Studenski SA, Chen WG, et al. Aging, the central nervous system, and mobility.J Gerontol A Biol Sci Med Sci. 2013; 68:1379–1386. doi: 10.1093/gerona/glt089.CrossrefMedlineGoogle Scholar6. Dumurgier J, Elbaz A, Dufouil C, Tavernier B, Tzourio C.Hypertension and lower walking speed in the elderly: the Three-City study.J Hypertens. 2010; 28:1506–1514. doi: 10.1097/HJH.0b013e328338bbec.CrossrefMedlineGoogle Scholar7. Elbaz A, Shipley MJ, Nabi H, Brunner EJ, Kivimaki M, Singh-Manoux A.Trajectories of the Framingham general cardiovascular risk profile in midlife and poor motor function later in life: the Whitehall II study.Int J Cardiol. 2014; 172:96–102. doi: 10.1016/j.ijcard.2013.12.051.CrossrefMedlineGoogle Scholar8. Dumurgier J, Elbaz A, Ducimetière P, Tavernier B, Alpérovitch A, Tzourio C.Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study.BMJ. 2009; 339:b4460.CrossrefMedlineGoogle Scholar9. Soumaré A, Elbaz A, Zhu Y, Maillard P, Crivello F, Tavernier B, Dufouil C, Mazoyer B, Tzourio C.White matter lesions volume and motor performances in the elderly.Ann Neurol. 2009; 65:706–715. doi: 10.1002/ana.21674.CrossrefMedlineGoogle Scholar10. Dumurgier J, Crivello F, Mazoyer B, Ahmed I, Tavernier B, Grabli D, François C, Tzourio-Mazoyer N, Tzourio C, Elbaz A.MRI atrophy of the caudate nucleus and slower walking speed in the elderly.Neuroimage. 2012; 60:871–878. doi: 10.1016/j.neuroimage.2012.01.102.CrossrefMedlineGoogle Scholar11. Tchalla AE, Wellenius GA, Travison TG, Gagnon M, Iloputaife I, Dantoine T, Sorond FA, Lipsitz LA.Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults.Hypertension. 2015; 66:340–346. doi: 10.1161/HYPERTENSIONAHA.115.05180.LinkGoogle Scholar12. Kallmann BA, Hummel V, Lindenlaub T, Ruprecht K, Toyka KV, Rieckmann P.Cytokine-induced modulation of cellular adhesion to human cerebral endothelial cells is mediated by soluble vascular cell adhesion molecule-1.Brain. 2000; 123(pt 4):687–697.CrossrefMedlineGoogle Scholar13. Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, Guralnik JM, Ferrucci L.Inflammatory markers and physical performance in older persons: the InCHIANTI study.J Gerontol A Biol Sci Med Sci. 2004; 59:242–248.CrossrefMedlineGoogle Scholar14. Dumurgier J, Singh-Manoux A, Tavernier B, Tzourio C, Elbaz A.Lipid-lowering drugs associated with slower motor decline in the elderly adults.J Gerontol A Biol Sci Med Sci. 2014; 69:199–206. doi: 10.1093/gerona/glt140.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Tchalla A, Wellenius G, Boyer S, Travison T, Habtemariam D, Gagnon M, Iloputaife I, Sorond F, Dantoine T and Lipsitz L (2018) High levels of an endothelial dysfunction marker (sVCAM-1) are associated with injurious and recurrent falls and mortality over a 5-year interval in an older population, Experimental Gerontology, 10.1016/j.exger.2018.02.020, 106, (1-7), Online publication date: 1-Jun-2018. Guzik T and Touyz R (2017) Oxidative Stress, Inflammation, and Vascular Aging in Hypertension, Hypertension, 70:4, (660-667), Online publication date: 1-Oct-2017. August 2015Vol 66, Issue 2 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.115.05437PMID: 26056338 Originally publishedJune 8, 2015 PDF download Advertisement SubjectsHypertension