Cerebral white matter changes are associated with abnormalities on neurological examination in non-disabled elderly: the LADIS study

Abstract

Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a 3-year period and their possible associations with WMC in a cohort of initially non-disabled elderly subjects. Data from the multicenter Leukoaraiosis And DISability study were used. A standard neurological examination was performed at baseline and at each of the annual follow-up visits. A standard MRI scan was performed at baseline and after 3-years. WMC severity was graded as mild, moderate, or severe on the Fazekas scale, while the Rotterdam scale was used to assess progression. Infarcts and their occurrence were also assessed. Six hundred and thirty-nine non-disabled subjects were enrolled (mean age 74.1 ± 5.0, M/F: 288/351). Severe WMC at baseline were associated with gait and stance abnormalities, upper motor signs, and fingertap slowing. This effect was independent of age, sex, lacunar and non-lacunar infarcts. The occurrence of stance abnormalities, upper motor signs, primitive reflexes and fingertap slowing during the 3-year follow-up period was associated with both baseline WMC load and their progression. The occurrence of the same abnormalities plus extrapyramidal and primitive reflexes was associated with incident lacunar infarcts. In our cohort of non-disabled elders, severe WMC were associated with the presence and the occurrence of neurological signs, independently of other vascular brain lesions, confirming that these lesions have clinical relevance.

Appendix

List of participating centers and personnel

Helsinki, Finland (Department of Neurology, Helsinki University Central Hospital and Department of Neurological Sciences, University of Helsinki, Finland): Timo Erkinjuntti, MD, PhD, Tarja Pohjasvaara, MD, PhD, Pia Pihanen, MD, Raija Ylikoski, PhD, Hanna Jokinen, PhD, Meija-Marjut Somerkoski, MPsych, Riitta Mäntylä, MD, PhD, Oili Salonen, MD, PhD; Graz, Austria (Department of Neurology and Department of Radiology, Division of Neuroradiology, Medical University Graz): Franz Fazekas, MD, Reinhold Schmidt, MD, Stefan Ropele, PhD, Brigitte Rous, MD, Katja Petrovic, MagPsychol, Ulrike Garmehi, Alexandra Seewann, MD; Lisboa, Portugal (Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria): José M. Ferro, MD, PhD, Ana Verdelho, MD, Sofia Madureira, PsyD, Carla Moleiro, PhD; Amsterdam, The Netherlands (Department of Radiology and Neurology, VU Medical Center): Philip Scheltens, MD, PhD, Ilse van Straaten, MD, Frederik Barkhof, MD, PhD, Alida Gouw, MD, Wiesje van der Flier, PhD; Goteborg, Sweden (Institute of Clinical Neuroscience, Goteborg University): Anders Wallin, MD, PhD, Michael Jonsson, MD, Karin Lind, MD, Arto Nordlund, PsyD, Sindre Rolstad, PsyD, Ingela Isblad, RN; Huddinge, Sweden (Karolinska Institutet, Department of Neurobiology, Care Sciences and Society; Karolinska University Hospital Huddinge): Lars-Olof Wahlund, MD, PhD, Milita Crisby, MD, PhD, Anna Pettersson, RPT, PhD, Kaarina Amberla, PsyD; Paris, France (Department of Neurology, Hopital Lariboisiere): Hugues Chabriat, MD, PhD, Karen Hernandez, psychologist, Annie Kurtz, psychologist, Dominique Hervé, MD, Sarah Benisty, MD, Jean Pierre Guichard, MD; Mannheim, Germany (Department of Neurology, University of Heidelberg, Klinikum Mannheim): Michael Hennerici, MD, Christian Blahak, MD, Hansjorg Baezner, MD, Martin Wiarda, PsyD, Susanne Seip, RN; Copenhagen, Denmark (Memory Disorders Research Group, Department of Neurology, Rigshospitalet, and the Danish Research Center for Magnetic Resonance, Hvidovre Hospital, Copenhagen University Hospitals): Gunhild Waldemar, MD, DMSc, Egill Rostrup, MD, MSc; Charlotte Ryberg, MSc, Tim Dyrby MSc, Olaf B. Paulson, MD, DMSc; Ellen Garde, MD, PhD; Kristian Steen Frederiksen, MD; Newcastle-upon-Tyne, UK (Institute for Ageing and Health, Newcastle University): John T. O’Brien, DM, Sanjeet Pakrasi, MRCPsych, Mani Krishnan MRCPsych, Andrew Teodorczuk, MRCPsych, Michael Firbank, PhD, Philip English, DCR, Thais Minett, MD, PhD.

The Coordinating centre is in Florence, Italy (Department of Neurological and Psychiatric Sciences, University of Florence): Domenico Inzitari, MD (Study Coordinator); Luciano Bartolini, PhD, Anna Maria Basile, MD, PhD, Eliana Magnani, MD, Monica Martini, MD, Mario Mascalchi, MD, PhD, Marco Moretti, MD, Leonardo Pantoni, MD, PhD, Anna Poggesi, MD, PhD, Giovanni Pracucci, MD, Emilia Salvadori, PhD, Michela Simoni, MD.

The LADIS Steering Committee is formed by Domenico Inzitari, MD (Study Coordinator), Timo Erkinjuntti, MD, PhD, Philip Scheltens, MD, PhD, Marieke Visser, MD, PhD, and Peter Langhorne, MD, BSC, PhD, FRCP who replaced in this role Kjell Asplund, MD, PhD beginning with 2005.