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Published Online
on March 6, 2008

Stroke. 2008
Published online before print March 6, 2008, doi: 10.1161/STROKEAHA.107.498535
A more recent version of this article appeared on May 1, 2008
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Submitted on July 6, 2007
Accepted on September 25, 2007

Progression of White Matter Hyperintensities and Incidence of New Lacunes Over a 3-Year Period. The Leukoaraiosis and Disability Study

Alida A. Gouw MD*; Wiesje M. van der Flier PhD; Franz Fazekas MD; Elisabeth C.W. van Straaten MD; Leonardo Pantoni MD, PhD; Anna Poggesi MD; Domenico Inzitari MD; Timo Erkinjuntti MD, PhD; Lars O. Wahlund MD, PhD; Gunhild Waldemar MD, DMSc; Reinhold Schmidt MD; Philip Scheltens MD, PhD; Frederik Barkhof MD, PhD; on behalf of the LADIS Study Group

From the Alzheimer Center (A.A.G., W.M.v.d.F., E.C.W.v.S., P.S., F.B.), the Departments of Neurology (A.A.G., W.M.v.d.F., E.C.W.v.S., P.S.), and Radiology (F.B.), and the Image Analysis Center (IAC) (A.A.G., E.C.W.v.S., F.B.), Vrije Universiteit Medical Center, Amsterdam, The Netherlands; the Department of Neurological and Psychiatric Sciences (L.P., A.P., D.I.), University of Florence, Florence, Italy; the Memory Research Unit, Department of Clinical Neurosciences (T.E.), Helsinki University, Helsinki, Finland; the Neurotec Department, Section of Clinical Geriatrics (L.O.W.), Karolinska Institute, Huddinge, Sweden; the Memory Disorders Research Unit, Department of Neurology (G.W.), Copenhagen University Hospital, Copenhagen, Denmark; and the Department of Neurology and MRI Institute (F.F., R.S.), Medical University, Graz, Austria.

* To whom correspondence should be addressed. E-mail: AA.Gouw{at}vumc.nl.

Background and Purpose—We studied the natural course of white matter hyperintensities (WMH) and lacunes, the main MRI representatives of small vessel disease, over time and evaluated possible predictors for their development.

Methods—Baseline and repeat MRI (3-year follow-up) were collected within the multicenter, multinational Leukoaraiosis and Disability study (n=396). Baseline WMH were scored on MRI by the Fazekas scale and the Scheltens scale. WMH progression was assessed using the modified Rotterdam Progression scale (absence/presence of progression in 9 brain regions). Baseline and new lacunes were counted per region. WMH and lacunes at baseline and vascular risk factors were evaluated as predictors of WMH progression and new lacunes.

Results—WMH progressed (mean±SD=1.9±1.8) mostly in the subcortical white matter, where WMH was also most prevalent at baseline. The majority of new lacunes, which were found in 19% of the subjects (maximum=9), also appeared in the subcortical white matter, mainly of the frontal lobes, whereas most baseline lacunes were located in the basal ganglia. Baseline WMH and lacunes predicted both WMH progression and new lacunes. Furthermore, previous stroke, diabetes, and blood glucose were risk factors for WMH progression. Male sex, hypertension, systolic blood pressure, previous stroke, body mass index, high-density lipoprotein, and triglyceride levels were risk factors for new lacunes.

Conclusion—WMH and lacunes progressed over time, predominantly in the subcortical white matter. Progression was observed especially in subjects with considerable WMH and lacunes at baseline. Moreover, the presence of vascular risk factors at baseline predicted WMH progression and new lacunes over a 3-year period.


Key words: lacunes • leukoaraiosis • MRI • risk factors • white matter disease