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.
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.
Inzitari
Domenico
D
Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Firenze, Italy. inzitari@neuro.unifi.it
Pracucci
Giovanni
G
Poggesi
Anna
A
Carlucci
Giovanna
G
Barkhof
Frederik
F
Chabriat
Hugues
H
Erkinjuntti
Timo
T
Fazekas
Franz
F
Ferro
José M
JM
Hennerici
Michael
M
Langhorne
Peter
P
O'Brien
John
J
Scheltens
Philip
P
Visser
Marieke C
MC
Wahlund
Lars-Olof
LO
Waldemar
Gunhild
G
Wallin
Anders
A
Pantoni
Leonardo
L
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