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Age, Hypertension, and Lacunar Stroke Are the Major Determinants of the Severity of Age-Related White Matter Changes
The LADIS (Leukoaraiosis and Disability in the Elderly) StudyBasile A.M.a · Pantoni L.a · Pracucci G.a · Asplund K.b · Chabriat H.c · Erkinjuntti T.d · Fazekas F.e · Ferro J.M.f · Hennerici M.G.g · O’Brien J.h · Scheltens P.i · Visser M.C.i · Wahlund L.-O.j · Waldemar G.k · Wallin A.l · Inzitari D.a
aDepartment of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy; bSocialstyrelsen National Board of Health and Welfare, Stockholm, Sweden; cDepartment of Neurology, Hôpital Lariboisière, Paris, France; dMemory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, Finland; eDepartment of Neurology and MRI Institute, Karl-Franzens University Graz, Graz, Austria; fServiço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria Lisboa, Lisboa, Portugal; gDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany; hInstitute for Ageing and Health, University of Newcastle, Newcastle-upon-Tyne, UK; iDepartment of Neurology, VU Medical Center, Amsterdam, The Netherlands; jKarolinska Institutet, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden; kMemory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark; lInstitute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden
Background: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. Methods: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1 ± 5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. Results: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. Conclusions: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.
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