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Leukoaraiosis Predicts Hidden Global Functioning Impairment in Nondisabled Older People: The LADIS (Leukoaraiosis and Disability in the Elderly) Study

Authors

  • Leonardo Pantoni MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Anna Poggesi MD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Anna Maria Basile MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Giovanni Pracucci MD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Frederik Barkhof MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Hugues Chabriat MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Timo Erkinjuntti MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • José M. Ferro MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Michael Hennerici MD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • John O'Brien DM,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Reinhold Schmidt MD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Marieke C. Visser MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Lars-Olof Wahlund MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Gunhild Waldemar MD, DMSc,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Anders Wallin MD, PhD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • Domenico Inzitari MD,

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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  • on behalf of the LADIS Study Group

    1. From the *Department of Neurological and Psychiatric Sciences, University of Florence, Florence, ItalyDepartment of Neurology, VU Medical Center, Amsterdam, the NetherlandsDepartment of Neurology, Hôpital Lariboisiere, Paris, France§Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, FinlandDepartment of Neurology, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, PortugalDepartment of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany#Institute for Aging and Health, University of Newcastle, Newcastle-upon-Tyne, United Kingdom**Department of Neurology and MRI Institute, Medical University Graz, Austria††Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden‡‡Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark§§Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden.
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Address correspondence to Leonardo Pantoni, MD, PhD, Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. E-mail: pantoni@neuro.unifi.it

Abstract

OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients.

DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study.

SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people.

PARTICIPANTS: Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age±standard deviation 74.1±5.0) with magnetic resonance imaging–detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified.

MEASUREMENTS: Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning.

RESULTS: At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score.

CONCLUSION: Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.

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