Physical activity in the elderly is associated with improved executive function and processing speed: the LADIS Study Kristian Steen Frederiksen 1 , Ana Verdelho 2 , Sofia Madureira 2 , Hansjörg Bäzner 3 , John T. O’Brien 4 , Franz Fazekas 5 , Philip Scheltens 6 , Reinhold Schmidt 5 , Anders Wallin 7 , Lars-Olof Wahlund 8 , Timo Erkinjunttii 9 , Anna Poggesi 10 , Leonardo Pantoni 10 , Domenico Inzitari 10 , Gunhild Waldemar 1 and on behalf of the LADIS Study 1 Memory Disorders Research Group, Danish Dementia Research Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark 2 Department of Neurosciences, University of Lisbon, Santa Maria Hospital, Lisbon, Portugal 3 Department of Neurology, University of Heidelberg, Klinikum Mannheim, Mannheim, Germany 4 Department of Psychiatry, University of Cambridge and Cambridgeshire and Peterborough NHS Trust, Cambridge, UK 5 Department of Neurology, Medical University Graz, Austria 6 Department of Neurology, VU Medical Center, Amsterdam, The Netherlands 7 Institute of Clinical Neuroscience, Göteborg University, Göteborg, Sweden 8 Department of Clinical Neuroscience, NEUROTEC, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden 9 Memory Research Unit, Department of Clinical Neurosciences, Helsinki University, Helsinki, Finland 10 Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy Correspondence to: K. S. Frederiksen, E-mail: kristian.steen.frederiksen@regionh.dk Objectives: Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes (ARWMC). Methods: Data from the Leukoaraiosis And DISability (LADIS) study, a multicenter, European prospective co- hort study aimed at examining the role of ARWMC in transition to disability, was used. Subjects in the LADIS study were clinically assessed yearly for 3 years including MRI at baseline and 3-year follow-up. Physical activity was assessed at baseline, and cognitive compound scores at baseline and 3-year assessment were used. Results: Two-hundred-eighty-two subjects (age, y (mean (SD)): 73.1 (±5.1); gender (f/m): 164/118); MMSE (mean (SD)): 28.3 (±1.7)) who had not progressed to MCI or dementia, were included. Multi- ple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3-year follow-up for executive function (baseline: β: 0.39, 95% CI: 0.13–0.90, p = 0.008; follow-up: β: 0.24, 95% CI: 0.10–0.38, p = 0.001) and processing speed (baseline: β: 0.48, 95% CI: 0.14–0.89, p = 0.005; follow-up: β: 0.15, 95% CI: 0.02–0.29, p = 0.02) but not memory. When including baseline cognitive score as a covariate in the analysis of 3-year follow-up scores, executive function remained significant (β: 0.11, 95% CI: 0–0.22, p = 0.04). Conclusion: Our findings confirm previous findings of a positive effect of physical activity on cognitive functions in elderly subjects, and further extends these by showing that the association is also present in patients with ARWMC. Copyright # 2014 John Wiley & Sons, Ltd. Key words: physical activity; cognitive; executive function; memory; processing speed; age-related white matter changes History: Received 25 January 2014; Accepted 5 September 2014; Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/gps.4220 Introduction The benefits of a physically active lifestyle are many including a reduced risk of cardiovascular disease and type 2 diabetes (Warburton et al. 2006). Numer- ous studies have also shown that physical activity reduces the risk of decline in global cognitive function and progression to dementia (Lindsay, 2002; Kivipelto Copyright # 2014 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry 2014 RESEARCH ARTICLE