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The LADIS Study

Domenico Inzitari, MD; Michela Simoni, MD; Giovanni Pracucci, MD; Anna Poggesi, MD; Anna Maria Basile, MD, PhD; Hugues Chabriat, MD, PhD; Timo Erkinjuntti, MD, PhD; Franz Fazekas, MD; José M. Ferro, MD, PhD; Michael Hennerici, MD; Peter Langhorne, MD, BSc, PhD, FRCP; John O'Brien, DM; Frederik Barkhof, MD, PhD; Marieke C. Visser, MD, PhD; Lars-Olof Wahlund, MD, PhD; Gunhild Waldemar, MD, DMSc; Anders Wallin, MD, PhD; Leonardo Pantoni, MD, PhD; for the LADIS Study Group

Arch Intern Med. 2007;167(1):81-88.

Background  Age-related white matter changes (ARWMCs), frequently detected on neuroimaging, are associated with motor, cognitive, urinary, and mood disorders. The LADIS (LeukoAraiosis and DISability) Study primarily aims to assess ARWMCs as a determinant of global functional decline in the elderly population.

Methods  We enrolled 639 patients (mean age, 74.1 ± 5.0 years; 45.1% male) referred for nondisabling complaints, who had ARWMCs detected on brain magnetic resonance imaging (MRI) of mild, moderate, or severe grade according to the Fazekas scale. At the 1-year follow-up, 619 were reassessed using the Instrumental Activities of Daily Living (IADL) scale. Of these, 506 were totally independent at baseline, and 113 were impaired in only 1 item of the IADL scale. We studied the 1-year transition to 2 or more activities limited and selective functional impairments as cofactors of functional decline.

Results  The rate of transition was 9%, 15%, and 26%, in the mild, moderate, and severe ARWMC group, respectively. Comparing the severe with the mild ARWMC groups and adjusting for age and for other predictors of decline, the risk was more than 2-fold higher (odds ratio; 2.38; 95% confidence interval, 1.29-4.38) in patients with 0 or 1 activity limited, and 3-fold higher (odds ratio, 3.02; 95% confidence interval, 1.34-6.78) among patients fully independent at baseline. Both motor and cognitive deterioration predominantly explained the effect of ARWMCs on global functional decline.

Conclusion  Elderly patients who are functionally independent and who have severe ARWMCs are at considerable risk of becoming more dependent in a short period, mostly owing to motor and cognitive deterioration.

Author Affiliations: Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy (Drs Inzitari, Simoni, Pracucci, Poggesi, Basile, and Pantoni); Department of Neurology, Hôpital Lariboisiere, Paris, France (Dr Chabriat); Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, Finland (Dr Erkinjuntti); Department of Neurology and MRI Institute, Medical University Graz, Graz, Austria (Dr Fazekas); Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisboa, Portugal (Dr Ferro); Department of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany (Dr Hennerici); Academic Department for Geriatric Medicine, Glasgow Royal Infirmary, Glasgow, Scotland (Dr Langhorne); Institute for Ageing and Health, University of Newcastle, Newcastle-upon-Tyne, England (Dr O'Brien); Department of Radiology and Neurology, VU Medical Center, Amsterdam, the Netherlands (Drs Barkhof and Visser); Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden (Dr Wahlund,); Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark (Dr Waldemar); and Institute of Clinical Neuroscience, Goteborg University, Goteborg, Sweden (Dr Wallin).

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