Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort

Article type: Research Article

Authors: Kramberger, Milica G.^{a; b} | Auestad, Bjørn^c | Garcia-Ptacek, Sara^{d; e} | Abdelnour, Carla^f | Olmo, Josep Garre^g | Walker, Zuzana^h | Lemstra, Afina W.ⁱ | Londos, Elisabet^j | Blanc, Frederic^k | Bonanni, Laura^l | McKeith, Ian^m | Winblad, Bengt^b | de Jong, Frank Janⁿ | Nobili, Flavio^o | Stefanova, Elka^p | Petrova, Maria^q | Falup-Pecurariu, Cristian^r | Rektorova, Irena^s | Bostantjopoulou, Sevasti^t | Biundo, Roberta^u | Weintraub, Daniel^v | Aarsland, Dag^{b; w; x; *} | on behalf of the E-DLB

Affiliations: [a] Department of Neurology, University Medical Centre, Ljubljana, Slovenia | [b] Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden | [c] Research Department, Stavanger University Hospital and Department of Mathematics and Natural Sciences, The University of Stavanger, Stavanger, Norway | [d] Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden | [e] Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden | [f] Fundació ACE Institut Català de Neurociències Aplicades, Barcelona, Spain | [g] Girona Biomedical Research Institute, Girona, Spain | [h] Division of Psychiatry, University College London and North Essex Partnership University NHS Foundation Trust, UK | [i] Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands | [j] Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden | [k] Service of Neurology and Geriatrics, University Hospital of Strasbourg and Icube laboratory, University of Strasbourg, France | [l] Clinical Memory Research Unit, Department of Clinical Sciences, Department of Neuroscience and Imaging and Aging Research Centre, G. d’Annunzio University, Chieti, Italy | [m] Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK | [n] Erasmus MC – University Medical Center, Rotterdam, The Netherlands | [o] Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Italy | [p] Institute of Neurology CCS, School of Medicine, University of Belgrade, Belgrade, Serbia | [q] University Hospital “Alexandrovska”, Department of Neurology, Sofia, Bulgaria | [r] Department of Neurology, County Emergency Clinic Hospital, Faculty of Medicine, Transilvania University, Brasov, Romania | [s] Brain and Mind Research Program, Central European Institute of Technology, Central European Institute of Technology Masaryk University, Masaryk University, Brno, Czech Republic | [t] 3rd Department of Neurology, Medical School, Aristotle University of Thessaloniki, Greece | [u] Center for Parkinson’s disease and Movement Disorder “Fondazione Ospedale San Camillo” - Istituto di Ricovero e Cura a Carattere Scientifico, Venice-Lido, Italy | [v] Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA | [w] Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK | [x] Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway

Correspondence: [*] Correspondence to: Dag Aarsland, Professor and Head of Department, Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, PO. Box P070, De Crespigny Park, London SE5 8AF, UK. Tel.: +44 0207 848 0548; E-mails: [email protected]; [email protected].

Abstract: Background/Objective: The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD) patients. Methods: Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time. Several subgroup analyses were performed, defined by anti-dementia medication use, baseline MMSE score, and DLB core features. Results: The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p = 0.07 compared to DLB) and 1.8 in PDD (p = 0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features. Conclusions: The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.

Keywords: Dementia with Lewy bodies, international cohort, long-term cognitive decline, multicenter study

DOI: 10.3233/JAD-161109

Journal: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 787-795, 2017