Pharmacoepidemiology report
Benzodiazepine use and risk of dementia: A nested case–control study

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Abstract

The objective of this article was to examine the possible association between benzodiazepine use and the risk of dementia in the elderly. This was a nested case–control study set in community settings in Bordeaux area, France. The participants were a representative sample of 3,777 elderly persons (65 years of age and older) followed from 1989 to 1997. The main outcome measures were the use of benzodiazepines in incident cases of dementia versus nondemented controls. On the basis of medical and psychological data, 150 patients were diagnosed with dementia according to the criteria of the third revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of patient's medicine chest by a trained neuropsychologist. After controlling for age, gender, education level, living alone, wine consumption, psychiatric history, and depressive symptomatology, ever use of benzodiazepines was associated with a significantly increased risk of dementia [adjusted odds ratio (OR), 1.7; 95% confidence interval, 1.2–2.4]. Former use was associated with a significantly increased risk of dementia (adjusted OR, 2.3; 95% CI,1.2–4.5). No association was found between dementia and the current use of benzodiazepines (adjusted OR, 1.0; 95% CI, 0.6–1.6). Our finding suggest that former use of benzodiazepines could be a risk factor for dementia, but more detailed investigation are needed.

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.

Section snippets

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.

References (39)

  • P Cherin et al.

    Risk of syncope in the elderly and consumption of drugsa case–control study

    J Clin Epidemiol

    (1997)
  • O.S Miettinen et al.

    Principles of nonexperimental assessment of excess risk, with special reference to adverse drug reactions

    J Clin Epidemiol

    (1989)
  • P.D Nowell et al.

    Benzodiazepines and zolpidem for chronic insomniaa meta-analysis of treatment efficacy

    JAMA

    (1997)
  • K Morgan

    Hypnotics in the elderly. What cause for concern?

    Drugs

    (1990)
  • G.D Mellinger et al.

    Prevalence and correlates of the long-term regular use of anxiolytics

    JAMA

    (1984)
  • R.I Shorr et al.

    Rational use of benzodiazepines in the elderly

    Drugs Aging

    (1994)
  • Lecomte T. La consommation pharmaceutique en 1988, évolution 1980–1988.Rapport C.R.E.D.E.S, 1991;888. Available at...
  • Guignon N, Mormiche P, Sermet C. La consommation régulière de psychotropes. INSEE Première 1994;310. Available at...
  • E Zarifian

    Presciption of psychotropic drugs; use, misuse and abuse

    Bull Acad Natl Med

    (1998)
  • R.I Shader et al.

    Use of benzodiazepines in anxiety disorders

    N Engl J Med

    (1993)
  • J.M Starr et al.

    Drug-induced dementia

    Drug Saf

    (1994)
  • J.D Bowen et al.

    Drug-induced cognitive impairment. Defining the problem and finding solutions

    Drugs Aging

    (1993)
  • H.S Koelega

    Benzodiazepines and vigilance performancea review

    Psychopharmacology (Berlin)

    (1989)
  • R.I Block et al.

    Memory performance in individuals with primary degenerative dementiaits similarity to diazepam-induced impairments

    Exp Aging Res

    (1985)
  • R.A Bornstein et al.

    Effects of chronic benzodiazepine administration on neuropsychological performance

    Clin Neuropharmacol

    (1985)
  • C.G Swift et al.

    Side-effect “tolerance” in elderly long-term recipients of benzodiazepine hypnotics

    Age Ageing

    (1984)
  • U Busto et al.

    Withdrawal reaction after long-term therapeutic use of benzodiazepines

    N Engl J Med

    (1986)
  • D.J Greenblatt et al.

    Sensitivity to triazolam in the elderly

    N Engl J Med

    (1991)
  • D.J Greenblatt et al.

    Implications of altered drug disposition in the elderlystudies of benzodiazepines

    J Clin Pharmacol

    (1989)
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