Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia

Objectives: We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5‐year follow‐up. Methods: This is a longitudinal analysis of a Norwegi...

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Autores:
Borda, Miguel Germán
Jaramillo-Jimenez, Alberto
Oesterhus, Ragnhild
Santacruz, José Manuel
Tovar Ríos, Diego Alejandro
Soennesyn, Hogne
Cano-Gutierrez, Carlos
Vik-Mo, Audun Osland
Aarsland, Dag
Tipo de recurso:
Article of journal
Fecha de publicación:
2021
Institución:
Universidad Autónoma de Occidente
Repositorio:
RED: Repositorio Educativo Digital UAO
Idioma:
eng
OAI Identifier:
oai:red.uao.edu.co:10614/13923
Acceso en línea:
https://hdl.handle.net/10614/13923
https://red.uao.edu.co/
Palabra clave:
Estudio caso-control
Case-control method
Activities of daily living
Alzheimer's disease
Antidepressive Agent
Benzodiazepines
Cognitive decline
Dementia
Functional disability
Hypnotics and sedatives
Lewy body dementia
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openAccess
License
Derechos Reservados International Journal of Geriatric Psychiatry
id REPOUAO2_875c2c10164e00f5c30662d64d5b7e97
oai_identifier_str oai:red.uao.edu.co:10614/13923
network_acronym_str REPOUAO2
network_name_str RED: Repositorio Educativo Digital UAO
repository_id_str
dc.title.eng.fl_str_mv Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia
title Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia
spellingShingle Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia
Estudio caso-control
Case-control method
Activities of daily living
Alzheimer's disease
Antidepressive Agent
Benzodiazepines
Cognitive decline
Dementia
Functional disability
Hypnotics and sedatives
Lewy body dementia
title_short Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia
title_full Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia
title_fullStr Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia
title_full_unstemmed Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia
title_sort Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia
dc.creator.fl_str_mv Borda, Miguel Germán
Jaramillo-Jimenez, Alberto
Oesterhus, Ragnhild
Santacruz, José Manuel
Tovar Ríos, Diego Alejandro
Soennesyn, Hogne
Cano-Gutierrez, Carlos
Vik-Mo, Audun Osland
Aarsland, Dag
dc.contributor.author.none.fl_str_mv Borda, Miguel Germán
Jaramillo-Jimenez, Alberto
Oesterhus, Ragnhild
Santacruz, José Manuel
Tovar Ríos, Diego Alejandro
Soennesyn, Hogne
Cano-Gutierrez, Carlos
Vik-Mo, Audun Osland
Aarsland, Dag
dc.subject.armarc.spa.fl_str_mv Estudio caso-control
topic Estudio caso-control
Case-control method
Activities of daily living
Alzheimer's disease
Antidepressive Agent
Benzodiazepines
Cognitive decline
Dementia
Functional disability
Hypnotics and sedatives
Lewy body dementia
dc.subject.armarc.eng.fl_str_mv Case-control method
dc.subject.proposal.eng.fl_str_mv Activities of daily living
Alzheimer's disease
Antidepressive Agent
Benzodiazepines
Cognitive decline
Dementia
Functional disability
Hypnotics and sedatives
Lewy body dementia
description Objectives: We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5‐year follow‐up. Methods: This is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway” (DemVest). We included 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed annually for 5 years. Three prescription groups were defined: only benzodiazepines (BZD), only antidepressants (ADep), and the combination of benzodiazepines and antidepressants (BZD‐ADep). Linear mixed‐effects models were conducted to analyze the effect of the defined groups on the outcomes. The outcomes were functional decline, measured by the Rapid Disability Rating Scale—2, and cognition measured with the Mini‐Mental State Examination. Results: Prescription of the combination of benzodiazepines and antidepressants in LBD was associated with faster functional decline. In AD, the prescription of BZD and BZD‐ADep was associated with greater functional deterioration. ADep alone did not show positive or negative significant associations with the studied outcomes. Conclusions: BZD and especially the combination of BZD and ADep are associated with functional decline in AD and LBD and should be used cautiously
publishDate 2021
dc.date.issued.none.fl_str_mv 2021
dc.date.accessioned.none.fl_str_mv 2022-05-27T18:36:11Z
dc.date.available.none.fl_str_mv 2022-05-27T18:36:11Z
dc.type.spa.fl_str_mv Artículo de revista
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
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dc.type.content.eng.fl_str_mv Text
dc.type.driver.eng.fl_str_mv info:eu-repo/semantics/article
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dc.type.version.eng.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.issn.spa.fl_str_mv 10991166
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10614/13923
dc.identifier.instname.spa.fl_str_mv Universidad Autónoma de Occidente
dc.identifier.reponame.spa.fl_str_mv Repositorio Educativo Digital
dc.identifier.repourl.spa.fl_str_mv https://red.uao.edu.co/
identifier_str_mv 10991166
Universidad Autónoma de Occidente
Repositorio Educativo Digital
url https://hdl.handle.net/10614/13923
https://red.uao.edu.co/
dc.language.iso.eng.fl_str_mv eng
language eng
dc.relation.citationendpage.spa.fl_str_mv 925
dc.relation.citationstartpage.spa.fl_str_mv 917
dc.relation.citationvolume.spa.fl_str_mv 36
dc.relation.cites.eng.fl_str_mv Borda, M. G., Jaramillo Jiménez, A., Djonne Osterhus, R., Santacruz, J.M., Tovar Ríos, D.A., Soennesyn, H., Cano, C., Osland Vik-Mo, A., Aarsland, D. (2021). Benzodiazepines and antidepressants: effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia. International Journal of Geriatric Psychiatry. 36 (6), 917-925.
dc.relation.ispartofjournal.eng.fl_str_mv International Journal of Geriatric Psychiatry
dc.relation.references.none.fl_str_mv 1. Orgeta V, Mukadam N, Sommerlad A, Livingston G. The lancet commission on dementia prevention, intervention, and care: a call for action. Ir J Psychol Med. 2019;36(2):85‐88.
2. Alzheimer’s‐Association. Alzheimer's Disease facts and figures. Alzheimers Dement. 2020;16(2):391+.
3. Mueller C, Ballard C, Corbett A, Aarsland D. The prognosis of dementia with Lewy bodies. Lancet Neurol. 2017;16(5):390‐398.
4. Rongve A, Soennesyn H, Skogseth R, et al. Cognitive decline in dementia with Lewy bodies: a 5‐year prospective cohort study. BMJ Open. 2016;6:e010357.
5. Borda MG, Soennesyn H, Steves CJ, Osland Vik‐Mo A, Pérez‐Zepeda MU, Aarsland D. Frailty in older adults with mild dementia: dementia with Lewy bodies and Alzheimer’s disease. Dementia Geriatric Cognitive Disord Extra. 2019;9(1):176‐183.
6. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89(1):88‐100.
7. Reuben DB, Rubenstein LV, Hirsch SH, Hays RD. Value of functional status as a predictor of mortality: results of a prospective study. Am J Med. 1992;93(6):663‐669.
8. Bierman AS. Functional status: the six vital sign. J general Intern Med. 2001;16(11):785‐786.
9. Wilberforce M, Challis D, Davies L, Kelly MP, Roberts C, Loynes N. Person‐centredness in the care of older adults: a systematic review of questionnaire‐based scales and their measurement properties. BMC Geriatr. 2016;16(1):63.
10. Bjoerke‐Bertheussen BB, Bjoerke‐Bertheussen J, Ehrt U, Rongve A, Ballard C, Aarsland D. Neuropsychiatric symptoms in mild dementia with Lewy bodies and Alzheimer’s disease. Dementia Geriatric Cognitive Disord. 2012;34(1):1‐6.
11. Vik‐Mo AO, Giil LM, Borda MG, Ballard C, Aarsland D. The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12‐year longitudinal cohort study. Br J Psychiatry. 2019;216(1):43‐48. https://www.cambridge.org/core/journals/ the-british-journal-of-psychiatry/article/individual-course-of-neuro psychiatric-symptoms-in-people-with-alzheimers-and-lewy-bodydementia- 12year-longitudinal-cohort-study/03170C0BD3CE227 967FB7E8D296AC9D0
12. Rongve A, Vossius C, Nore S, Testad I, Aarsland D. Time until nursing home admission in people with mild dementia: comparison of dementia with Lewy bodies and Alzheimer's dementia. Int J Geriatr Psychiatry. 2014;29(4):392‐398.
13. Svendsboe E, Terum T, Testad I, et al. Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease. Int J Geriatr Psychiatry. 2016;31(9):1075‐1083.
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19. Patorno E, Glynn RJ, Levin R, Huybrechts KF. Benzodiazepines and the risk of all‐cause mortality in older patients. Innov Aging. 2018; 2(Suppl 1):852‐853.
20. Hessmann P, Dodel R, Baum E, et al. Prescription of benzodiazepines and related drugs in patients with mild cognitive deficits and Alzheimer’s disease. Pharmacopsychiatry. 2019;52(02):84‐91.
21. Alexopoulos GS. Depression in the elderly. Lancet. 2005;365(9475): 1961‐1970.
22. Neutel CI, Skurtveit S, Berg C. What is the point of guidelines? Benzodiazepine and z‐hypnotic use by an elderly population. Sleep Med. 2012;13(7):893‐897.
23. Fride Tvete I, Bjørner T, Skomedal T. Risk factors for excessive benzodiazepine use in a working age population: a nationwide 5‐year survey in Norway. Scand J Prim Health Care. 2015;33(4): 252‐259.
24. Oesterhus R, Aarsland D, Soennesyn H, Rongve A, Selbaek G, Kjosavik SR. Potentially inappropriate medications and drug‐drug interactions in home‐dwelling people with mild dementia. Int J Geriatr Psychiatry. 2017;32(2):183‐192.
25. Dyer AH, Murphy C, Lawlor B, Kennelly SP. Cognitive outcomes of long‐term benzodiazepine and related drug (BDZR) use in people living with mild to moderate Alzheimer's disease: results from NILVAD. J Am Med Dir Assoc. 2020;21(2):194‐200.
26. Baek YH, Lee H, Kim WJ, et al. Uncertain association between benzodiazepine use and the risk of dementia: a cohort study. J Am Med Dir Assoc. 2020;21(2):201‐211:e202.
27. Aarsland D, Rongve A, Nore SP, et al. Frequency and case identification of dementia with Lewy bodies using the revised consensus criteria. Dement Geriatr Cogn Disord. 2008;26(5):445‐452.
28. Vik‐Mo AO, Giil LM, Ballard C, Aarsland D. Course of neuropsychiatric symptoms in dementia: 5‐year longitudinal study. Int J Geriatr Psychiatry. 2018;33(10):1361‐1369.
29. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDSADRDA work group under the auspices of department of health and human services Task force on Alzheimer's disease. Neurology. 1984; 34(7):939‐944.
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35. Borda MG, Aarsland D, Tovar‐Rios DA, et al. Neuropsychiatric symptoms and functional decline in Alzheimer's disease and Lewy body dementia. J Am Geriatr Soc. 2020.
36. Borda MG, Jaramillo‐Jimenez A, Tovar‐Rios DA, et al. Hippocampal subfields and decline in activities of daily living in Alzheimer's disease and dementia with Lewy bodies. Neurodegener Dis Manag. 2020.
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39. Cummings JL, Mega M, Gray K, Rosenberg‐Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12): 2308‐2314.
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47. Tien SC, Chan HY, Hsu CC. The factors associated with inappropriate prescription patterns of benzodiazepines and related drugs among patients with dementia. Psychogeriatrics. 2020.20(4): 447–457. https://onlinelibrary.wiley.com/doi/full/10.1111/psyg. 12527
48. American geriatrics society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227‐2246. https://agsjournals.onlinelibrary.wiley. com/doi/abs/10.1111/jgs.13702
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dc.rights.spa.fl_str_mv Derechos Reservados International Journal of Geriatric Psychiatry
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spelling Borda, Miguel Germán14a783d386e18bc2ad422ed2be6960d8Jaramillo-Jimenez, Alberto7ba56013eca72dee1239149377194737Oesterhus, Ragnhild056afc7f7861d6b2286dc84d9571c546Santacruz, José Manuel7429281c7204977367ae03a2136d81b3Tovar Ríos, Diego Alejandro07060d11b8a5638f64193e3df953c80bSoennesyn, Hognecf99f779bbebbfe02b291dba6c22be51Cano-Gutierrez, Carlos4a7a12e58cc0ced452becd3d7a662272Vik-Mo, Audun Osland04f87172f1233d4dbf62b7ea29b1b95eAarsland, Dag1a74bad426808a6748d681f33fae72c82022-05-27T18:36:11Z2022-05-27T18:36:11Z202110991166https://hdl.handle.net/10614/13923Universidad Autónoma de OccidenteRepositorio Educativo Digitalhttps://red.uao.edu.co/Objectives: We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5‐year follow‐up. Methods: This is a longitudinal analysis of a Norwegian cohort study entitled “The Dementia Study of Western Norway” (DemVest). We included 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed annually for 5 years. Three prescription groups were defined: only benzodiazepines (BZD), only antidepressants (ADep), and the combination of benzodiazepines and antidepressants (BZD‐ADep). Linear mixed‐effects models were conducted to analyze the effect of the defined groups on the outcomes. The outcomes were functional decline, measured by the Rapid Disability Rating Scale—2, and cognition measured with the Mini‐Mental State Examination. Results: Prescription of the combination of benzodiazepines and antidepressants in LBD was associated with faster functional decline. In AD, the prescription of BZD and BZD‐ADep was associated with greater functional deterioration. ADep alone did not show positive or negative significant associations with the studied outcomes. Conclusions: BZD and especially the combination of BZD and ADep are associated with functional decline in AD and LBD and should be used cautiously9 páginasapplication/pdfengInternational journal of geriatric psychiatryDerechos Reservados International Journal of Geriatric Psychiatryhttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)http://purl.org/coar/access_right/c_abf2Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementiaArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Estudio caso-controlCase-control methodActivities of daily livingAlzheimer's diseaseAntidepressive AgentBenzodiazepinesCognitive declineDementiaFunctional disabilityHypnotics and sedativesLewy body dementia92591736Borda, M. G., Jaramillo Jiménez, A., Djonne Osterhus, R., Santacruz, J.M., Tovar Ríos, D.A., Soennesyn, H., Cano, C., Osland Vik-Mo, A., Aarsland, D. (2021). Benzodiazepines and antidepressants: effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia. International Journal of Geriatric Psychiatry. 36 (6), 917-925.International Journal of Geriatric Psychiatry1. Orgeta V, Mukadam N, Sommerlad A, Livingston G. The lancet commission on dementia prevention, intervention, and care: a call for action. Ir J Psychol Med. 2019;36(2):85‐88.2. Alzheimer’s‐Association. Alzheimer's Disease facts and figures. Alzheimers Dement. 2020;16(2):391+.3. Mueller C, Ballard C, Corbett A, Aarsland D. The prognosis of dementia with Lewy bodies. Lancet Neurol. 2017;16(5):390‐398.4. Rongve A, Soennesyn H, Skogseth R, et al. Cognitive decline in dementia with Lewy bodies: a 5‐year prospective cohort study. BMJ Open. 2016;6:e010357.5. Borda MG, Soennesyn H, Steves CJ, Osland Vik‐Mo A, Pérez‐Zepeda MU, Aarsland D. Frailty in older adults with mild dementia: dementia with Lewy bodies and Alzheimer’s disease. Dementia Geriatric Cognitive Disord Extra. 2019;9(1):176‐183.6. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89(1):88‐100.7. Reuben DB, Rubenstein LV, Hirsch SH, Hays RD. Value of functional status as a predictor of mortality: results of a prospective study. Am J Med. 1992;93(6):663‐669.8. Bierman AS. Functional status: the six vital sign. J general Intern Med. 2001;16(11):785‐786.9. Wilberforce M, Challis D, Davies L, Kelly MP, Roberts C, Loynes N. Person‐centredness in the care of older adults: a systematic review of questionnaire‐based scales and their measurement properties. BMC Geriatr. 2016;16(1):63.10. Bjoerke‐Bertheussen BB, Bjoerke‐Bertheussen J, Ehrt U, Rongve A, Ballard C, Aarsland D. Neuropsychiatric symptoms in mild dementia with Lewy bodies and Alzheimer’s disease. Dementia Geriatric Cognitive Disord. 2012;34(1):1‐6.11. Vik‐Mo AO, Giil LM, Borda MG, Ballard C, Aarsland D. The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12‐year longitudinal cohort study. Br J Psychiatry. 2019;216(1):43‐48. https://www.cambridge.org/core/journals/ the-british-journal-of-psychiatry/article/individual-course-of-neuro psychiatric-symptoms-in-people-with-alzheimers-and-lewy-bodydementia- 12year-longitudinal-cohort-study/03170C0BD3CE227 967FB7E8D296AC9D012. Rongve A, Vossius C, Nore S, Testad I, Aarsland D. Time until nursing home admission in people with mild dementia: comparison of dementia with Lewy bodies and Alzheimer's dementia. Int J Geriatr Psychiatry. 2014;29(4):392‐398.13. Svendsboe E, Terum T, Testad I, et al. Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease. 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Neurotherapeutics. 2020;17(1):156‐164.Comunidad generalPublicationLICENSElicense.txtlicense.txttext/plain; charset=utf-81665https://dspace7-uao.metacatalogo.com/bitstreams/47cc3b63-1159-455b-b2d8-28b8458c382a/download20b5ba22b1117f71589c7318baa2c560MD52ORIGINALBenzodiazepines and antidepressants - effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia.pdfBenzodiazepines and antidepressants - effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia.pdfTexto archivo completo del artículo de revista, PDFapplication/pdf417666https://dspace7-uao.metacatalogo.com/bitstreams/2f2466c9-caff-4770-9bab-d8ecaf287dad/download9f31668bafe2a56282522627b82732acMD53TEXTBenzodiazepines and antidepressants - effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia.pdf.txtBenzodiazepines and antidepressants - effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia.pdf.txtExtracted texttext/plain41391https://dspace7-uao.metacatalogo.com/bitstreams/158db228-2a60-4df3-a29a-736cffaf4ee8/download6d30d157be89881eafaf8dbe3793b948MD54THUMBNAILBenzodiazepines and antidepressants - effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia.pdf.jpgBenzodiazepines and antidepressants - effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia.pdf.jpgGenerated Thumbnailimage/jpeg17049https://dspace7-uao.metacatalogo.com/bitstreams/d837f3b6-89e9-4cc3-9475-d9832fa61685/downloadbb3ff06c1a49dd75b0184d8e8ed6c9d9MD5510614/13923oai:dspace7-uao.metacatalogo.com:10614/139232024-01-19 17:20:35.62https://creativecommons.org/licenses/by-nc-nd/4.0/Derechos Reservados International Journal of Geriatric Psychiatryopen.accesshttps://dspace7-uao.metacatalogo.comRepositorio UAOrepositorio@uao.edu.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