Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

doi:10.1136/bmj.b2477

Published 6 July 2009, doi:10.1136/bmj.b2477
Cite this as: BMJ 2009;339:b2477

Research

Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

Domenico Inzitari, full professor of neurology and chairman of the department¹, Giovanni Pracucci, neurologist¹, Anna Poggesi, neurologist PhD student¹, Giovanna Carlucci, assistant professor in neurology¹, Frederik Barkhof, full professor of neuroradiology², Hugues Chabriat, professor of neurology³, Timo Erkinjuntti, full professor of neurology⁴, Franz Fazekas, full professor of neurology⁵, José M Ferro, chairman professor of neurology⁶, Michael Hennerici, full professor of neurology and chairman of the department⁷, Peter Langhorne, full professor of geriatric medicine⁸, John O’Brien, professor of old age psychiatry⁹, Philip Scheltens, full professor of neurology², Marieke C Visser, assistant professor of neurology², Lars-Olof Wahlund, professor of geriatric medicine¹⁰, Gunhild Waldemar, full professor of neurology¹¹, Anders Wallin, full professor of neuropsychiatry¹², Leonardo Pantoni, consultant neurologist¹, on behalf of the LADIS Study Group

¹ Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Firenze, Italy, ² Department of Radiology and Neurology, VU Medical Centre, Amsterdam, Netherlands, ³ Department of Neurology, Hopital Lariboisiere, Paris, France, ⁴ Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, Finland, ⁵ Department of Neurology and MRI Institute, Medical University Graz, Austria, ⁶ Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria Lisboa, Portugal, ⁷ Department of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany, ⁸ Academic Department for Geriatric Medicine, Glasgow Royal Infirmary, Glasgow, ⁹ Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, ¹⁰ Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Karolinska University Hospital Huddinge, Huddinge, Sweden, ¹¹ Memory Disorders Research Unit, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark, ¹² Institute of Clinical Neuroscience, Gothenburg University, Gothenburg, Sweden

Correspondence to: D Inzitari inzitari{at}neuro.unifi.it

Objective To assess the impairment in daily living activitiesin older people with age related changes in white matter accordingto the severity of these changes.

Design Observational data collection and follow-up of a cohortof older people undergoing brain magnetic resonance imagingafter non-disabling complaints.

Setting 11 European centres.

Participants 639 non-disabled older patients (mean age 74.1(SD 5.0), 45.1% men) in whom brain magnetic resonance imagingshowed mild, moderate, or severe age related changes in whitematter (Fazekas scale). Magnetic resonance imaging assessmentalso included cerebral infarcts and atrophy.

Main outcome measure Transition from no disability (definedas a score of 0 or 1 on the instrumental activities of dailyliving scale) to disability (score $≥$ 2) or death over three yearfollow-up. Secondary outcomes were incident dementia and stroke.

Results Over a mean follow-up period of 2.42 years (SD 0.97,median 2.94 years), information on the main outcome was availablefor 633 patients. The annual rate of transition or death was10.5%, 15.1%, and 29.5%, respectively, for patients with mild,moderate, or severe age related changes in white matter (Kaplan-Meierlog rank test P<0.001). In a Cox model comparing severe withmild changes and adjusted for clinical factors of functionaldecline, the risk of transition to disability or death was morethan twofold higher (hazard ratio 2.36, 95% confidence interval1.65 to 3.81). The other predictors were age group, historyof atrial fibrillation, and complaint of gait disturbances.The effect of severe changes remained significant independentlyof baseline degree of atrophy and number of infarcts. Incidentstroke and dementia only slightly modified this effect.

Conclusion The three year results of the LADIS study suggestthat in older adults who seek medical attention for non-disablingcomplaints, severe age related changes in white matter independentlyand strongly predict rapid global functional decline.

© Inzitari et al 2009
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to StumbleUpon StumbleUpon Add to Technorati Technorati What's this?

Relevant Article

Osteoarthritis and protection from global functional decline: David J Robinson and Diarmuid O’Shea
BMJ 2009 339: b3352. [Extract] [Full Text]

This article has been cited by other articles:

Robinson, D. J, O'Shea, D. (2009). Osteoarthritis and protection from global functional decline. BMJ 339: b3352-b3352 [Full text]
(2009). Age-Related White Matter Changes Predict Functional Decline. JWatch General 2009: 6-6 [Full text]

Rapid Responses:

Read all Rapid Responses

Disability in the elderly: the protective effect of osteoarthritis: David J Robinson, et al.
bmj.com, 23 Jul 2009 [Full text]
Leukoaraiosis and Cognitive Fundtion: Rizaldy Pinzon
bmj.com, 3 Aug 2009 [Full text]