title: Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort.
abstract: OBJECTIVE
  To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes.
  
  
  METHODS
  Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints.
  
  
  METHODS
  11 European centres.
  
  
  METHODS
  639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy.
  
  
  METHODS
  Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score >/=2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke.
  
  
  RESULTS
  Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect.
  
  
  CONCLUSIONS
  The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.
authors: Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Firenze, Italy. inzitari@neuro.unifi.it
authors: Domenico
authors: D
authors: Inzitari
authors: Giovanni
authors: G
authors: Pracucci
authors: Anna
authors: A
authors: Poggesi
authors: Giovanna
authors: G
authors: Carlucci
authors: Frederik
authors: F
authors: Barkhof
authors: Hugues
authors: H
authors: Chabriat
authors: Timo
authors: T
authors: Erkinjuntti
authors: Franz
authors: F
authors: Fazekas
authors: José M
authors: JM
authors: Ferro
authors: Michael
authors: M
authors: Hennerici
authors: Peter
authors: P
authors: Langhorne
authors: John
authors: J
authors: O'Brien
authors: Philip
authors: P
authors: Scheltens
authors: Marieke C
authors: MC
authors: Visser
authors: Lars-Olof
authors: LO
authors: Wahlund
authors: Gunhild
authors: G
authors: Waldemar
authors: Anders
authors: A
authors: Wallin
authors: Leonardo
authors: L
authors: Pantoni
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology; D015331:Cohort Studies; D003704:Dementia / Q000473:pathology; D006233:Persons with Disabilities; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D049292:Leukoaraiosis / Q000473:pathology* / Q000534:rehabilitation; D008279:Magnetic Resonance Imaging; D008297:Male; D012017:Referral and Consultation; D012307:Risk Factors; D020521:Stroke / Q000473:pathology