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(Stroke. 2008;39:1414.)
© 2008 American Heart Association, Inc.

Original Contributions

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.

Correspondence to Alida A. Gouw, MD, Department of Neurology, Alzheimer Center and Image Analysis Center, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. 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