Galantamine treatment in Alzheimer’s disease with cerebrovascular disease: responder analyses from a randomized, controlled trial (GAL-INT-6) T Erkinjuntti Memory Research Unit, Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. S Gauthier McGill Center for Studies in Aging, Montreal, QC, Canada. R Bullock Kingshill Research Centre, Department of Old Age Psychiatry, Swindon, UK. A Kurz Technische Universität München, Munich, Germany. G Hammond Janssen-Cilag European Medical Affairs, High Wycombe, UK and Neuss Germany. S Schwalen Janssen-Cilag European Medical Affairs, High Wycombe, UK and Neuss Germany. Y Zhu Ortho-McNeil Janssen Scientific Affairs, L.L.C., Titusville, NJ, USA. R Brashear Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Titusville, NJ, USA. Journal of Psychopharmacology 22(7) (2008) 761–768 © 2008 British Association for Psychopharmacology ISSN 0269-8811 SAGE Publications Los Angeles, London, New Delhi and Singapore 10.1177/0269881107083028 Original Papers Introduction There is growing evidence that Alzheimer’s disease (AD) frequently co-exists with significant cerebrovascular (CVD) pathol- ogy (Jellinger, 2002; Jellinger and Attems, 2006; Jellinger, 2007). Clinically, this overlap is AD with cerebrovascular disease (AD with CVD). The term ‘mixed dementia’ is sometimes used to describe this condition, but is also used to describe vascular demen- tia with both cortical and subcortical features so AD  CVD is more precise. Clinical differentiation of AD from AD with stroke history or vascular risk factors is complicated by symptom overlap (Lopez et al., 2005; Jellinger, 2007). A diagnosis of AD does not preclude the presence of CVD, and dual diagnosis is important. Relative with AD alone, AD with CVD may involve a more Abstract Alzheimer’s disease combined with cerebrovascular disease (AD with CVD) is associated with progressive decline, with CVD impacting AD onset and severity of progression. Subjects with confirmed diagnosis of AD with CVD were treated with galantamine during a six-month, randomized, placebo-controlled trial (N  285). Responder analyses were performed for cognitive, behavioural and functional outcome measures. Galantamine treatment resulted in significantly greater cognitive and functional improvements compared with placebo at six months, and a significantly higher percentage of treatment responders. The proportion of responders demonstrating improved or maintained cognition on the 11-item AD assessment scale-cognitive subscale (ADAS-cog/11) was 60.5% for galantamine versus 46.0% for placebo (P  0.013). The proportion of patients responding by at least four-points on the ADAS-cog/11 was signifi- cantly greater for the galantamine group compared with placebo (33.6% versus 17.2%; P  0.003). Seventy-five percent of galantamine-treated subjects improved or remained stable as assessed by CIBIC-plus compared with 53.6% on placebo (P  0.0006). Significantly higher responder rates were observed with galantamine for behaviour (64.9% versus 56.6%; P  0.024), and numeri- cally favourable responder rates were seen with galantamine for activities of daily living. Treatment-emergent adverse events were generally related with the gastrointestinal system (nausea 20% versus 10%; vomiting 12% versus 5%; galantamine and placebo groups, respectively). Three deaths occurred during double-blind treatment: 2 of 188 subjects receiving galantamine, and 1 of 97 subjects receiving placebo. These findings are consistent with a broad range of cognitive, functional and behavioural benefits with galantamine across the spectrum of AD and AD with CVD. Keywords Alzheimer disease, dementia, cerebrovascular accident, cardiovascular dis- eases, vascular dementias, galantamine Corresponding author: Dr Susanne Schwalen, Janssen-Cilag GmbH, Raiffeisenstrasse 8, 41470 Neuss, Germany. Email: sschwale@jacde.jnj.com at Technical University of Munich University Library on November 3, 2016 jop.sagepub.com Downloaded from