title: Use of benzodiazepines and related drugs is associated with a risk of stroke among persons with Alzheimer's disease.
abstract: The aim of our study was to investigate the risk of any, ischemic, and hemorrhagic stroke associated with incident benzodiazepine and related drug (BZDR) use among community-dwelling individuals with Alzheimer's disease (AD). Data from the MEDALZ cohort including all community-dwelling persons newly diagnosed with AD between 2005 and 2011 in Finland were utilized. Incident BZDR users were identified with a 1-year washout period for previous use. Persons with a previous stroke were excluded, resulting in a final study sample of 45 050 individuals. Incident any, ischemic, and hemorrhagic strokes were identified from the Hospital Discharge and Causes of Death registers. The risk of stroke between time on BZDRs was compared with nonuse time with Cox proportional hazard models. During the follow-up, 21.9% (N=9879) of persons started BZDR use. Compared with nonuse, BZDR use was associated with an increased risk of any stroke [adjusted hazard ratio (aHR): 1.21; 95% confidence interval (CI): 1.04-1.40] and ischemic stroke (aHR: 1.21; 95% CI: 1.02-1.44), but the association between BZDR use and hemorrhagic stroke did not reach significance (aHR: 1.26; 95% CI: 0.91-1.74). Z-drug use was associated with a similar risk as benzodiazepine use. In conclusion, BZDR use was associated with an increased risk of stroke among older individuals with AD.
authors.affiliation: aKuopio Research Centre of Geriatric Care bSchool of Pharmacy cDepartment of Forensic Psychiatry, Niuvanniemi Hospital dResearch Centre for Comparative Effectiveness and Patient Safety (RECEPS) eInstitute of Clinical Medicine, University of Eastern Finland fKuopio University Hospital, Psychiatric Clinic, Kuopio gNational Institute for Health and Welfare hCentre for Research Methods, Department of Social Research, University of Helsinki, Helsinki iDepartment of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland jDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Heidi
authors.initials: H
authors.lastname: Taipale
authors.forename: Marjaana
authors.initials: M
authors.lastname: Koponen
authors.forename: Antti
authors.initials: A
authors.lastname: Tanskanen
authors.forename: Piia
authors.initials: P
authors.lastname: Lavikainen
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Tolppanen
authors.forename: Reijo
authors.initials: R
authors.lastname: Sund
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.forename: Sirpa
authors.initials: S
authors.lastname: Hartikainen
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000453:epidemiology; D001569:Benzodiazepines / Q000009:adverse effects*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D012042:Registries; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology*
chemical_list: D001569:Benzodiazepines