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


CONCLUSIONS
There is a dose-response relationship between cumulative anticholinergic and sedative drug use and hospitalization and mortality in people with and without AD.
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.
Danijela
D
Gnjidic
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.
Sarah N
SN
Hilmer
Kuopio Research Centre of Geriatric Care, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Sirpa
S
Hartikainen
Department of Neurology, University of Eastern Finland, Kuopio, Finland.
Anna-Maija
AM
Tolppanen
Kuopio Research Centre of Geriatric Care, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Heidi
H
Taipale
Kuopio Research Centre of Geriatric Care, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Marjaana
M
Koponen
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.
J Simon
JS
Bell
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000401:mortality*; D018680:Cholinergic Antagonists / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D063487:Prescription Drug Misuse / Q000706:statistics & numerical data*; D012044:Regression Analysis; D012307:Risk Factors
D018680:Cholinergic Antagonists; D006993:Hypnotics and Sedatives