title: Deterioration of gait and balance over time: the effects of age-related white matter change--the LADIS study.
abstract: BACKGROUND
  Cross-sectional studies have shown an association between the severity of age-related white matter change (ARWMC) and lower body motor function. However, the association between prevalent ARWMC and incident deterioration of balance and gait remains insufficiently investigated. This study investigates if the degree of prevalent ARWMC has a differential effect on lower body motor function as it changes over time, hypothesizing that individuals with more severe baseline white matter pathology experience greater clinical deterioration independent of potential confounders. This is of clinical relevance: given the increasing use of neuroimaging, incidental white matter pathology is common; being able to delineate natural trajectories of balance and gait function given ARWMC may improve patient advice and help optimize allocation of care.
  
  
  METHODS
  639 non-disabled elderly individuals with prevalent ARWMC (grading of severity of ARWMC using the Fazekas scale) were followed up yearly for 3 years, as part of the Leukoaraiosis and Disability Study. The primary outcome variable, reflecting the temporal course of gait and balance function, was the change of scores on the Short Physical Performance Battery (SPPB) over time versus the severity of ARWMC. We used linear mixed modelling to analyse change over time. Explorative analysis was carried out investigating the effect of age on potential deterioration of gait and balance function. We used propensity scores to adjust for multiple confounders that affect both the exposure (i.e. ARWMC) and outcome.
  
  
  RESULTS
  Subjects' lower body motor function deteriorated by 2.6% per year. However, after adjustment for baseline motor impairment and potential confounders, only subjects with moderate [-0.22 points per year on the SPPB (equals -2.3%); 95% CI -0.35 to -0.09, p < 0.001] or severe [-0.46 points per year (equals -4.7%); 95% CI -0.63 to -0.28, p < 0.0001] ARWMC show a loss of function. Age shows differential effects: relatively younger elderly subjects have similar temporal dynamics in SPPB change independent of their individual degree of ARWMC severity; however, subjects with severe ARWMC and who are older than 75.9 years deteriorate significantly more rapidly than their counterparts with only mild or moderate white matter pathology.
  
  
  CONCLUSIONS
  Only moderate and severe ARWMC is independently associated - on average - with a deterioration of gait and balance. Albeit the possibility of unmeasured confounding and other methodological constraints, there is nonetheless evidence of large interindividual variability: some subjects with moderate or severe ARWMC stay stable over time or even show improvement. Furthermore, there is explorative analysis showing that younger elderly subjects may be able to better compensate even severe ARWMC. These individuals' gait and balance function stays relatively stable over time, whereas their older counterparts deteriorate significantly. This may point towards a threshold effect given ARWMC.
authors.affiliation: Department of Neurology, University of Heidelberg, UniversitätsMedizin Mannheim, Mannheim, Germany. stefan.kreisel@evkb.de
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Kreisel
authors.forename: Christian
authors.initials: C
authors.lastname: Blahak
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Bäzner
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pantoni
authors.forename: Anna
authors.initials: A
authors.lastname: Poggesi
authors.forename: Hugues
authors.initials: H
authors.lastname: Chabriat
authors.forename: Timo
authors.initials: T
authors.lastname: Erkinjuntti
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.forename: José M
authors.initials: JM
authors.lastname: Ferro
authors.forename: Peter
authors.initials: P
authors.lastname: Langhorne
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Marieke C
authors.initials: MC
authors.lastname: Visser
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.forename: Gunhild
authors.initials: G
authors.lastname: Waldemar
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hennerici
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D006233:Persons with Disabilities / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D005684:Gait / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors