Neelesh K Nadkarni1, Robert M Boudreau2, Stephanie A Studenski2, Oscar L Lopez2, Ge Liu2, Stephen Kritchevsky2, Kristine Yaffe2, Anne B Newman2, Caterina Rosano2. 1. From the Division of Geriatric Medicine and Gerontology, Department of Medicine (N.K.N.), Department of Neurology (O.L.L.) and the Pittsburgh Alzheimer's Disease Research Center (O.L.L., N.K.N.), University of Pittsburgh School of Medicine, and Department of Epidemiology, Graduate School of Public Health (R.M.B., G.L., A.B.N., C.R.), University of Pittsburgh, PA; Sticht Center on Aging (S.K.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Psychiatry (K.Y.), University of California at San Francisco; and the Longitudinal Studies Section (S.A.S.), Translational Gerontology Branch, National Institute on Aging, Baltimore, MD. nkn3@pitt.edu. 2. From the Division of Geriatric Medicine and Gerontology, Department of Medicine (N.K.N.), Department of Neurology (O.L.L.) and the Pittsburgh Alzheimer's Disease Research Center (O.L.L., N.K.N.), University of Pittsburgh School of Medicine, and Department of Epidemiology, Graduate School of Public Health (R.M.B., G.L., A.B.N., C.R.), University of Pittsburgh, PA; Sticht Center on Aging (S.K.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Psychiatry (K.Y.), University of California at San Francisco; and the Longitudinal Studies Section (S.A.S.), Translational Gerontology Branch, National Institute on Aging, Baltimore, MD.
Abstract
OBJECTIVE: To examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship. METHODS: In 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics. RESULTS: In this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (β = -0.27, p < 0.001) and to higher WMH (β = 0.23, p = 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p = 0.043) in the mediation analyses. CONCLUSIONS: Sustained exposure to high IL-6 over 10 years rather than the rate of change in IL-6 or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH.
OBJECTIVE: To examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship. METHODS: In 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics. RESULTS: In this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (β = -0.27, p < 0.001) and to higher WMH (β = 0.23, p = 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p = 0.043) in the mediation analyses. CONCLUSIONS: Sustained exposure to high IL-6 over 10 years rather than the rate of change in IL-6 or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH.
Authors: Stephen M Smith; Mark Jenkinson; Mark W Woolrich; Christian F Beckmann; Timothy E J Behrens; Heidi Johansen-Berg; Peter R Bannister; Marilena De Luca; Ivana Drobnjak; David E Flitney; Rami K Niazy; James Saunders; John Vickers; Yongyue Zhang; Nicola De Stefano; J Michael Brady; Paul M Matthews Journal: Neuroimage Date: 2004 Impact factor: 6.556
Authors: Nicola Moscufo; Charles R G Guttmann; Dominik Meier; Istvan Csapo; Peter G Hildenbrand; Brian C Healy; Julia A Schmidt; Leslie Wolfson Journal: Neurobiol Aging Date: 2009-05-09 Impact factor: 4.673
Authors: Nancy S Jenny; Benjamin French; Alice M Arnold; Elsa S Strotmeyer; Mary Cushman; Paulo H M Chaves; Jingzhong Ding; Linda P Fried; Stephen B Kritchevsky; Dena E Rifkin; Mark J Sarnak; Anne B Newman Journal: J Gerontol A Biol Sci Med Sci Date: 2012-02-24 Impact factor: 6.053
Authors: Marius de Groot; Benjamin F J Verhaaren; Renske de Boer; Stefan Klein; Albert Hofman; Aad van der Lugt; M Arfan Ikram; Wiro J Niessen; Meike W Vernooij Journal: Stroke Date: 2013-02-21 Impact factor: 7.914
Authors: K Yaffe; K Lindquist; B W Penninx; E M Simonsick; M Pahor; S Kritchevsky; L Launer; L Kuller; S Rubin; T Harris Journal: Neurology Date: 2003-07-08 Impact factor: 9.910
Authors: Brenda W J H Penninx; Stephen B Kritchevsky; Anne B Newman; Barbara J Nicklas; Eleanor M Simonsick; Susan Rubin; Michael Nevitt; Marjolein Visser; Tamara Harris; Marco Pahor Journal: J Am Geriatr Soc Date: 2004-07 Impact factor: 5.562
Authors: Brianne M Bettcher; Christa L Watson; Christine M Walsh; Iryna V Lobach; John Neuhaus; Joshua W Miller; Ralph Green; Nihar Patel; Shubir Dutt; Edgar Busovaca; Howard J Rosen; Kristine Yaffe; Bruce L Miller; Joel H Kramer Journal: PLoS One Date: 2014-09-04 Impact factor: 3.240
Authors: Dana R Jorgensen; C Elizabeth Shaaban; Clayton A Wiley; Peter J Gianaros; Joseph Mettenburg; Caterina Rosano Journal: Am J Physiol Heart Circ Physiol Date: 2018-02-02 Impact factor: 4.733
Authors: Line Jee Hartmann Rasmussen; Avshalom Caspi; Antony Ambler; Jonathan M Broadbent; Harvey J Cohen; Tracy d'Arbeloff; Maxwell Elliott; Robert J Hancox; HonaLee Harrington; Sean Hogan; Renate Houts; David Ireland; Annchen R Knodt; Kim Meredith-Jones; Miriam C Morey; Lynda Morrison; Richie Poulton; Sandhya Ramrakha; Leah Richmond-Rakerd; Maria L Sison; Kate Sneddon; W Murray Thomson; Ahmad R Hariri; Terrie E Moffitt Journal: JAMA Netw Open Date: 2019-10-02
Authors: Gordon W Blair; Maria Valdez Hernandez; Michael J Thrippleton; Fergus N Doubal; Joanna M Wardlaw Journal: Curr Treat Options Cardiovasc Med Date: 2017-07