title: Slow gait, white matter characteristics, and prior 10-year interleukin-6 levels in older adults.
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.
authors.affiliation: 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.
authors.forename: Neelesh K
authors.initials: NK
authors.lastname: Nadkarni
authors.affiliation: 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.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Boudreau
authors.affiliation: 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.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Studenski
authors.affiliation: 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.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: 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.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kritchevsky
authors.affiliation: 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.
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
authors.affiliation: 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.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.affiliation: 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.
authors.forename: Caterina
authors.initials: C
authors.lastname: Rosano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting / Q000097:blood; D005260:Female; D020233:Gait Disorders, Neurologic / Q000097:blood* / Q000503:physiopathology*; D006801:Humans; D057187:Independent Living; D015850:Interleukin-6 / Q000097:blood*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6