Hostname: page-component-76fb5796d-22dnz Total loading time: 0 Render date: 2024-04-29T01:49:26.824Z Has data issue: false hasContentIssue false
  • English
  • Français

Benzodiazepine use and risk of incident MCI and dementia in a community sample

Published online by Cambridge University Press:  26 May 2023

Esther G. Teverovsky Open the ORCID record for Esther G. Teverovsky [Opens in a new window] ,
Ariel Gildengers ,
Xinhui Ran ,
Erin Jacobsen ,
Chung-Chou H. Chang  and
Mary Ganguli Open the ORCID record for Mary Ganguli [Opens in a new window]
Esther G. Teverovsky*
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Ariel Gildengers
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Xinhui Ran
Affiliation:
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
Erin Jacobsen
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Chung-Chou H. Chang
Affiliation:
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Mary Ganguli
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
*
Correspondence should be addressed to: Esther G. Teverovsky, WPH of UPMC, 3811 O’Hara Street, Pittsburgh, PA 15213, USA. Phone: 412-246-6274; Fax: 412-586-9300. Email: teverovskyeg@upmc.edu.
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives:

Older adults commonly take benzodiazepines (BZDs) that may have long-term adverse cognitive effects. We investigated whether BZD use was related to developing mild cognitive impairment (MCI) or dementia in cognitively normal older adults in the community.

Setting/Participants:

A population-based cohort (n = 1959) of adults aged 65 and over, recruited from communities of low socioeconomic status.

Measurements:

BZD use, Clinical Dementia Rating (CDR), anxiety symptoms, depression symptoms, sleep difficulties, and APOE genotype.

Design:

We examined time from study entry to MCI (CDR = 0.5) and time from study entry to dementia (CDR ≥ 1) in participants who were cognitively normal at baseline (CDR = 0). We used survival analysis (Cox model), adjusted for age, sex, education, sleep, anxiety, and depression. For all the models, we included an interaction term between BZD use and APOE*4.

Results:

Taking BZDs was significantly associated with higher risk of developing MCI, but not of developing dementia. The effect was not affected by APOE genotype.

Conclusions:

In a population-based sample of cognitively normal older adults, BZD use is associated with developing MCI, but not dementia. BZD use may be a potentially modifiable risk factor for MCI.

Keywords

anti-anxiety agentsagingepidemiology
Type
Original Research Article
Information
International Psychogeriatrics , Volume 36 , Special Issue 2: Issue Theme: Psycho-Bio-Social Risk Factors and Dementia , February 2024 , pp. 142 - 148
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of International Psychogeriatric Association

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

The work reported here was supported in part by grant R37AG023651 from the National Institute on Aging, National Institutes of Health, US DHHS.

References

Aldaz, P. et al. (2021). |Association between benzodiazepine use and development of dementia. Medicina Clinica, 156, 107–111.CrossRefGoogle ScholarPubMed
Andreescu, C., Teverovsky, E., Fu, B., Hughes, T. F., Chang, C.-C. H. and Ganguli, M. (2014). Old worries and new anxieties: behavioral symptoms and mild cognitive impairment in a population study. The American Journal of Geriatric Psychiatry, 22, 274–284.CrossRefGoogle ScholarPubMed
Baek, Y. H. et al. (2020). Uncertain association between benzodiazepine use and the risk of dementia: a cohort study. Journal of the American Medical Directors Association, 21, 201–211.e2.CrossRefGoogle ScholarPubMed
Billioti de Gage, S. et al. (2012). Benzodiazepine use and risk of dementia: prospective population based study. BMJ, 345, e6231.CrossRefGoogle ScholarPubMed
Brown, T. A., Antony, M. M. and Barlow, D. H. (1992). Psychometric properties of the Penn state worry questionnaire in a clinical anxiety disorders sample. Behaviour Research and Therapy, 30, 33–37.CrossRefGoogle Scholar
Chiu, H. Y. et al. (2021). Comparative efficacy and safety of hypnotics for insomnia in older adults: a systematic review and network meta-analysis. Sleep, 44, zsaa260.CrossRefGoogle ScholarPubMed
Curran, H. V., Collins, R., Fletcher, S., Kee, S. C. Y., Woods, B. and Iliffe, S. (2003). Older adults and withdrawal from benzodiazepine hypnotics in general practice: effects on cognitive function, sleep, mood and quality of life. Psychological Medicine, 33, 1223–1237.CrossRefGoogle ScholarPubMed
Desmidt, T. et al. (2019). Benzodiazepine use and brain amyloid load in nondemented older individuals: a florbetapir PET study in the Multidomain Alzheimer Preventive Trial cohort. Neurobiology of Aging, 84, 61–69.CrossRefGoogle ScholarPubMed
Dyer, A. H. et al. (2021). Long-term anticholinergic, benzodiazepine and Z-drug use in community-dwelling older adults: What is the impact on cognitive and neuropsychological performance? International Journal of Geriatric Psychiatry, 36, 1767–1777.CrossRefGoogle ScholarPubMed
Ferreira, P., Ferreira, A. R., Barreto, B. and Fernandes, L. (2022). Is there a link between the use of benzodiazepines and related drugs and dementia? A systematic review of reviews. European Geriatric Medicine, 13, 19–32.CrossRefGoogle Scholar
Folstein, M. F., Folstein, S. E. and McHugh, P. R. (1975). Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.CrossRefGoogle Scholar
Furukawa, T., Nikaido, Y., Shimoyama, S., Masuyama, N., Notoya, A. and Ueno, S. (2021). Impaired cognitive function and hippocampal changes following chronic diazepam treatment in middle-aged mice. Frontiers in Aging Neuroscience, 13, 777404.CrossRefGoogle ScholarPubMed
Gallacher, J., Elwood, P., Pickering, J., Bayer, A., Fish, M. and Ben-Shlomo, Y. (2012). Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS). Journal of Epidemiology and Community Health, 66, 869–873.CrossRefGoogle ScholarPubMed
Ganguli, M., Chang, C.-C. H., Snitz, B. E., Saxton, J. A., Vanderbilt, J. and Lee, C.-W. (2010). Prevalence of mild cognitive impairment by multiple classifications: the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) project. The American Journal of Geriatric Psychiatry, 18, 674–683.CrossRefGoogle ScholarPubMed
Ganguli, M. et al. (2014). Vascular risk factors and cognitive decline in a population sample. Alzheimer Disease & Associated Disorders, 28, 9–15.CrossRefGoogle Scholar
Ganguli, M., Gilby, J., Seaberg, E. and Belle, S. (1995). Depressive symptoms and associated factors in a rural elderly population: the MoVIES project. The American Journal of Geriatric Psychiatry, 3, 144–160.CrossRefGoogle Scholar
Ganguli, M. et al. (2019). Mild cognitive impairment that does not progress to dementia: a population-based study. Journal of the American Geriatrics Society, 67, 232–238.CrossRefGoogle Scholar
Gerlach, L. B., Myra Kim, H., Ignacio, R. V., Strominger, J. and Maust, D. T. (2021). Use of benzodiazepines and risk of incident dementia: a retrospective cohort study. The Journals of Gerontology: Series A, 77, 1035–1041.Google Scholar
Goddard, A. W., Brouette, T., Almai, A., Jetty, P., Woods, S. W. and Charney, D. (2001). Early coadministration of clonazepam with sertraline for panic disorder. Archives of General Psychiatry, 58, 681–686.CrossRefGoogle ScholarPubMed
Gomm, W. et al. (2016). Regular benzodiazepine and Z-substance use and risk of dementia: an analysis of German claims data. Journal of Alzheimer’s Disease, 54, 801–808.CrossRefGoogle ScholarPubMed
Gray, S. L. et al. (2016). Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ, 352, i90.CrossRefGoogle ScholarPubMed
Grossi, C. M. et al. (2019). Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study. BMC Geriatrics, 19, 276.CrossRefGoogle ScholarPubMed
Hafdi, M., Hoevenaar-Blom, M. P., Beishuizen, C. R. L., Moll van Charante, E. P., Richard, E. and van Gool, W. A. (2020). Association of benzodiazepine and anticholinergic drug usage with incident dementia: a prospective cohort study of community-dwelling older adults. Journal of the American Medical Directors Association, 21, 188–193.e3.CrossRefGoogle ScholarPubMed
Hata, T. et al. (2018). What can predict and prevent the long-term use of benzodiazepines? Journal of Psychiatric Research, 97, 94–100.CrossRefGoogle ScholarPubMed
Hu, C., Yu, D., Sun, X., Zhang, M., Wang, L. and Qin, H. (2017). The prevalence and progression of mild cognitive impairment among clinic and community populations: a systematic review and meta-analysis. International Psychogeriatrics, 29, 1595–1608.CrossRefGoogle ScholarPubMed
Joyce, G., Ferido, P., Thunell, J., Tysinger, B. and Zissimopoulos, J. (2022). Benzodiazepine use and the risk of dementia. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 8, e12309.Google ScholarPubMed
Lagnaoui, R. et al. (2008). The risk of cognitive impairment in older community-dwelling women after benzodiazepine use. Age and Ageing, 38, 226–228.CrossRefGoogle ScholarPubMed
Lin, C. E. et al. (2020). Association between concurrent antidepressant and hypnotic treatment and the risk of dementia: a nationwide cohort study. Journal of Affective Disorders, 277, 549–558.CrossRefGoogle ScholarPubMed
Lucchetta, R. C., da Mata, B. P. M. and Mastroianni, P. C. (2018). Association between development of dementia and use of benzodiazepines: a systematic review and meta-analysis. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 38, 1010–1020.CrossRefGoogle ScholarPubMed
Mitchell, A. J. and Shiri-Feshki, M. (2009). Rate of progression of mild cognitive impairment to dementia – meta-analysis of 41 robust inception cohort studies. Acta Psychiatrica Scandinavica, 119, 252–265.CrossRefGoogle ScholarPubMed
Mitra, P. (2022). A systematic review and meta-analysis of the risk of dementia associated with benzodiazepine use, after controlling for protopathic bias. In: Tampi, R. R., Tampi, D. J., Young, J. J., Balasubramaniam, M. and Joshi, P. (Eds.), Essential Reviews in Geriatric Psychiatry (pp 35–38). Cham: Springer International Publishing.CrossRefGoogle Scholar
Morris, J. C. (1993). Current vision and scoring rules the clinical dementia rating (CDR). Neurology, 43, 2412–2414.CrossRefGoogle Scholar
Mungas, D., Marshall, S., Weldon, M., Haan, M. and Reed, B. R. (1996). Age and education correction of Mini-Mental State Examination for English-and Spanish-speaking elderly. Neurology, 46, 700–706.CrossRefGoogle ScholarPubMed
Nader, D. and Gowing, L. (2020). Is long-term benzodiazepine use a risk factor for cognitive decline? Results of a systematic review. Journal of Addiction, 2020, 1569456.CrossRefGoogle ScholarPubMed
Nafti, M., Sirois, C., Kröger, E., Carmichael, P.-H. and Laurin, D. (2020). Is benzodiazepine use associated with the risk of dementia and cognitive impairment-not dementia in older persons? The Canadian Study of Health and Aging. Annals of Pharmacotherapy, 54, 219–225.CrossRefGoogle ScholarPubMed
Penninkilampi, R. and Eslick, G. D. (2018). A systematic review and meta-analysis of the risk of dementia associated with benzodiazepine use, after controlling for protopathic bias. CNS Drugs, 32, 485–497.CrossRefGoogle ScholarPubMed
Qian, J. et al. (2017). APOE-related risk of mild cognitive impairment and dementia for prevention trials: an analysis of four cohorts. PLoS Medicine, 14, e1002254.CrossRefGoogle ScholarPubMed
R-Core-Team (2020). A Language and Environment For Statistical Computing. Vienna, Austria: R-Core-Team.Google Scholar
Radloff, L. S. (1977). The CES-D Scale: a self-report depression scale for research in the general population. Applied Psychological Measurement, 1, 385–401.CrossRefGoogle Scholar
Shash, D. et al. (2016). Benzodiazepine, psychotropic medication, and dementia: a population-based cohort study. Alzheimer’s & Dementia, 12, 604–613.Google ScholarPubMed