title: Cerebral White Matter and Slow Gait: Contribution of Hyperintensities and Normal-appearing Parenchyma.
abstract: White matter hyperintensities (WMH), a common marker of cerebral small vessel disease, and lower microstructural integrity of normal-appearing white matter are associated with slower gait. How these cerebral measures interact in relation to slower gait is unknown. We assessed whether microstructural integrity of normal-appearing white matter, measured by fractional anisotropy (FA), moderates the association of higher WMH with slower gait.
  
  
  
  WMH, FA, and gait speed were acquired for 265 community-dwelling older adults (average age = 82.9 years).
  
  
  
  The inverse association between WMH and gait was robust to adjustment for age, gender, muscle strength, obesity, stroke, and hypertension (fully adjusted model: βs = -0.19, p = .001). The interaction between WMH and FA was significant; analyses stratified by FA showed that the inverse association between WMH and gait speed was significant only for those with low FA (FA < median, fully adjusted model: βs = -0.28, p = .001). Voxel-based results were similar for participants with FA less than median, there was an inverse association between gait speed and WMH which extended throughout the white matter (genu and body of corpus callosum, anterior limb of internal capsule, corona radiata, and superior longitudinal and fronto-occipital fasciculus). In contrast, for participants with FA ≥ median, the association was limited to the genu of corpus callosum, the cingulum, and the inferior longitudinal fasciculus.
  
  
  
  Microstructural integrity is a moderating factor in the association between WMH and gait. Future studies should examine whether higher microstructural integrity represents a source of compensation in those with greater WMH burden to maintain function in late life.
authors.affiliation: Department of Epidemiology and blr5@pitt.edu.
authors.forename: Bedda L
authors.initials: BL
authors.lastname: Rosario
authors.affiliation: Department of Epidemiology and.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Rosso
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
authors.affiliation: Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, Maryland.
authors.forename: Tamara
authors.initials: T
authors.lastname: Harris
authors.affiliation: Department of Epidemiology and.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Satterfield
authors.affiliation: Longitudinal Studies Section, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Studenski
authors.affiliation: Department of Psychiatry, University of California, San Francisco.
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
authors.affiliation: Department of Epidemiology and.
authors.forename: Caterina
authors.initials: C
authors.lastname: Rosano
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D016880:Anisotropy; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D005684:Gait / Q000502:physiology*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D056784:Leukoencephalopathies / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008297:Male; D012307:Risk Factors; D013223:Statistics as Topic; D000072797:Walking Speed / Q000502:physiology*; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
keywords: DTI; Fractional anisotropy; Gait speed; Normal-appearing white matter; White matter hyperintensities