Pharmacoepidemiology reportBenzodiazepine use and risk of dementia: A nested case–control study
Introduction
Benzodiazepines (BZDs) are among the most frequently used drugs in the elderly population 1, 2, 3, 4, 5, 6, 7. They have well known acute effects on cognition 8, 9, 10, 11, 12, 13, 14, 15, which may be worse in the elderly because of changes in pharmacokinetic parameters or pharmacodynamic responsiveness 16, 17, 18, 19. Long-term use of benzodiazepines may be associated with impairment of performance [20]. However, Fastbom et al. [21], in a cohort study of 668 persons, aged 75 years and older, followed during 3 years, reported a significantly lower incidence of dementia in elderly persons using BZDs.
The link between BZD and dementia could be multifold: for Fastbom et al. [21], the increased GABAergic transmission associated with BZD opposes the deleterious effects of the neuroexcitotoxicity transmetter glutamate, which may be involved in the emergence of dementia. On the other hand, the cognitive effects of BZD and especially memory impairment closely mimick those observed during dementia [12]. The use of BZD in susceptible patients could trigger the onset or worsen the symptoms of dementia. To help clarify this apparent contradiction, we undertook a nested case–control study in a large representative cohort of French community dwelling elderly, to examine the association between BZD use and the occurrence of dementia.
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Study design and population
The data for this study were obtained from the PAQUID (Personnes Agées Quid) Research Program, a prospective epidemiological survey of a representative noninstitutionalized sample of persons over the age of 65 living in the Bordeaux area (Gironde and Dordogne), France, selected from electoral lists 22, 23. The main objective of the PAQUID study was to determine the incidence, risk factors, and early manifestations of dementia. The sample was stratified according to gender, age, and size of the
Results
Out of the 3,777 subjects recruited in the PAQUID cohort, 3,654 (97.7%) were eligible for the analysis: 102 prevalent cases of dementia identified at baseline and 21 cases identified at the first follow-up 1 year later were excluded. From this eligible population, 150 cases of incident dementia and 3,519 controls were selected. Characteristics of cases and controls are outlined in Table 1. Cases were more likely to be women, to have a depressive symptomatology, to have a lower educational
Discussion
This nested case–control study showed that ever use of benzodiazepines was associated with a small increased risk of dementia. The probable effect could be due to former use, while current use did not seem to increase the risk. If confirmed, the association of BZDs with an increased risk of dementia could be of major consequence because (1) the use of benzodiazepines is high in the elderly, and (2) the incidence of dementia is very high in these age classes. But, like other studies conducted on
Acknowledgements
This study was supported by a grant of the Fondation pour la Recherche Médicale and of l'Agence Française de Sécurité Sanitaire des Produits de Santé. We thank Drs Miriam Sturkenboom, Lucien Abenhaim for their valuable comments.
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