Impact of high risk drug use on hospitalization and mortality in older people with and without Alzheimer's disease: a national population cohort study

Danijela Gnjidic; Sarah N Hilmer; Sirpa Hartikainen; Anna-Maija Tolppanen; Heidi Taipale; Marjaana Koponen; J Simon Bell

doi:10.1371/journal.pone.0083224

Impact of high risk drug use on hospitalization and mortality in older people with and without Alzheimer's disease: a national population cohort study

PLoS One. 2014 Jan 13;9(1):e83224. doi: 10.1371/journal.pone.0083224. eCollection 2014.

Authors

Danijela Gnjidic¹, Sarah N Hilmer², Sirpa Hartikainen³, Anna-Maija Tolppanen⁴, Heidi Taipale³, Marjaana Koponen³, J Simon Bell⁵

Affiliations

¹ Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia ; Departments of Clinical Pharmacology and Aged Care, and Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia ; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia ; Centre for Education and Research on Ageing and Concord RG Hospital, Sydney, New South Wales, Australia.
² Departments of Clinical Pharmacology and Aged Care, and Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia ; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
³ Kuopio Research Centre of Geriatric Care, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
⁴ Department of Neurology, University of Eastern Finland, Kuopio, Finland.
⁵ Kuopio Research Centre of Geriatric Care, School of Pharmacy, University of Eastern Finland, Kuopio, Finland ; Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia ; Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.

Abstract

Background: Evidence is lacking about outcomes associated with the cumulative use of anticholinergic and sedative drugs in people with Alzheimer's disease (AD). This retrospective cohort study investigated the relationship between cumulative exposure to anticholinergic and sedative drugs and hospitalization and mortality in people with and without AD in Finland.

Methods: Community-dwelling people aged 65 years and over, with AD on December 31(st) 2005 (n = 16,603) and individually matched (n = 16,603) comparison persons (age, sex, region of residence) were identified by the Social Insurance Institution of Finland. Drug utilization data were extracted from the Finnish National Prescription Register. Exposure to anticholinergic and sedative drugs was defined using the Drug Burden Index (DBI). Hospitalization and mortality data were extracted from national registers. Cox and zero-inflated negative binomial analyses were used to investigate the relationship between DBI and hospitalization and mortality over a one-year follow-up.

Results: In total, 5.8% of people with AD and 3.7% without AD died during 2006. For every unit increase in DBI, the adjusted hazard ratio for mortality was 1.21 (95% confidence intervals [CI]: 1.09-1.33) among people with AD, and 1.37 (95%CI: 1.20-1.56) among people without AD. Overall, 44.3% of people with AD and 33.4% without AD were hospitalized. When using no DBI exposure as the reference group, the adjusted incidence rate ratio for length of hospital stay among high DBI group (≥1) in people with AD was 1.15 (95%CI: 1.05-1.26) and 1.63 (95%CI: 1.41-1.88) in people without AD.

Conclusion: There is a dose-response relationship between cumulative anticholinergic and sedative drug use and hospitalization and mortality in people with and without AD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / mortality*
Cholinergic Antagonists / adverse effects*
Cohort Studies
Female
Finland / epidemiology
Hospitalization / statistics & numerical data*
Humans
Hypnotics and Sedatives / adverse effects*
Length of Stay / statistics & numerical data
Male
Prescription Drug Misuse / statistics & numerical data*
Regression Analysis
Risk Factors

Substances

Cholinergic Antagonists
Hypnotics and Sedatives

Grants and funding

This study was supported by the Alzheimer’s Australia Dementia Research Foundation. The sponsor had no role in the study design, data collection, data analysis, data interpretation, writing of this report or the decision to submit for publication. Danijela Gnjidic is supported by the Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship. Anna-Maija Tolppanen, Heidi Taipale, Marjaana Koponen and Sirpa Hartikainen acknowledge strategic funding received from the University of Eastern Finland, Faculty of Health Sciences.