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Preliminary Findings: Behavioral Worsening on Donepezil in Patients With Frontotemporal Dementia
Abstract
Objective The objective of this study was to evaluate donepezil, an acetylcholinesterase inhibitor, in the treatment of frontotemporal dementia (FTD). Methods Twelve patients with FTD who received donepezil for six months were compared with 12 FTD controls on behavioral measures. Results The groups did not differ on most variables at baseline or at six months; however, the donepezil group had greater worsening on the FTD Inventory. Four treated patients had increased disinhibited or compulsive acts, which abated with discontinuation of the medication. Conclusion There were no changes in global cognitive performance or dementia severity; however, a subgroup of patients with FTD can experience worsening of symptoms with donepezil.
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“In fact, some bvFTD patients may experience behavioral or cognitive deterioration when exposed to these agents [37].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [37]
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Khalili, E., Sodaei, F., Noroozıan, M., Michel, T. M., & Vafaee, M. S. (2026) · Journal of Neural Transmission · doi:10.1007/s00702-026-03158-4 · Cited by 1
“…indicated for AD and are not expected to benefit patients with FTD. Conversely, inappropriate treat - ment of FTD patients with AD-directed therapies, including acetylcholinesterase inhibitors, may exacerbate behavioral symptoms and worsen clinical outcomes (Wolz et al. 2016; Mendez et al. 2007).”
Emerging Symptomatic Treatment of Chronic Traumatic Encephalopathy (CTE): a narrative review
Rossi, C. A., Campese, N., & Colosimo, C. (2023) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2023.2224501 · Cited by 2
Update on Therapeutic Strategies for Atypical Parkinsonian Syndromes
Maghbooli, M., Mohammadzadeh, V., & Yousefi, M. (2020) · Türk Nöroloji Dergisi · doi:10.4274/tnd.2020.45467 · Cited by 1
“Acetylcholinesterase inhibitors (AChEIs) are sometimes used in CBD, it seems likely that the response to AChEIs in patients with CBD is related to phenotypes.”
BackgroundA case of frontotemporal dementia
Ting, H., Yashodhara, B., Yousuf, U. A. M., Dar, B., & Abas, A. (2013) · International Journal of Case Reports and Images · doi:10.5348/ijcri-2013-03-288-cr-9 · Cited by 1
Hashimoto, M. (2010) · Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics · doi:10.3143/geriatrics.47.294 · Cited by 1
Behavior Symptoms in Primary Progressive Aphasia Variants
Maruta, C., Marôco, J. P., de Mendonça, A., & Guerreiro, M. (2016) · Neuropsychiatric symptoms of neurological disease · doi:10.1007/978-3-319-39138-0_3 · Cited by 2
Dementia, Delirium, and Depression
Anderson, H. S. (2014) · Springer eBooks · doi:10.1007/978-1-4614-9047-0_6
Síntomas neuropsiquiátricos en la afasia progresiva primaria
Serrano, C. M., Dillon, C., Muñoz, D. M. C., Iturry, M., López, G. J. R., Bartoloni, L. C., Taragano, F. E., & Allegri, R. (2010) · Revista de Neurología · doi:10.33588/rn.5001.2009127 · Cited by 4
Boeve, B. F., & Boxer, A. L. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511581410.016 · Cited by 3
Dementia and Cognitive Impairment
Hugo, J., & Ganguli, M. (n.d.) · doi:10.4324/9780203047910-16 · Cited by 1
“In frontotemporal dementia, there is no convincing evidence of benefits from these drugs, and there are reports that they worsen behavior symptoms.(106,107)”
BackgroundOcampo, E., & Casas, B. (2026) · Journal of The American Geriatrics Society · doi:10.1111/jgs.70776
Zdunek, J., & Grodner, B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27209094
“Moreover, some clinical studies have reported worsening of behavioural symptoms in patients with FTD treated with cholinesterase inhibitors, including increased disinhibition and compulsive behaviours with donepezil [32].”
Iddir, S. P., Troy, E. A., Soble, J., & Kimchi, E. (2026) · Journal of Psychiatric Practice · doi:10.1097/pra.0000000000000934
Executive function and the feasibility of clinical trials for frontotemporal dementia
Coleman, K., & Finger, E. C. (2025) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2025.101466
“These include trials of memantine 2,5,6 and cholinesterase inhibitors, 7,8 in which symptomatic medications were effective for people with Alzheimer’s disease but not for those with FTD.”
Optineurin mutation-associated language variant frontotemporal dementia
Park, A., West, K., Darby, D. G., & Brodtmann, A. (2025) · BMJ Case Reports · doi:10.1136/bcr-2025-266544
“15 Although her FDG-PET scan was markedly asymmetric at the time of presentation, our patient was initially able to comprehend conversations.”
Early-Onset Alzheimer’s Disease, APOE4 And C9orf72 Expansion: A Case Report
Enrique-Benedito, T., Senoret, V., Sanchis, M., Penacho, V., Caracuel, Z., Arrizabalaga, M., Campoy, M. B., & Alcaraz, L. A. (2024) · Annals of Case Reports · doi:10.29011/2574-7754.101812
“The early and adequate diagnosis of these diseases is a challenge and to achieve this, it is essential to investigate the genetic bases of neurodegenerative pathologies in order to move towards personalized medicine [26,27].”
BackgroundDeath Toll by Dementia DrugPreprint
Lee, J.-H. (2021) · Research Square · doi:10.21203/rs.3.rs-384861/v4
Dementia Management Act and Death Toll by Dementia DrugPreprint
Lee, J.-H. (2021) · Research Square · doi:10.21203/rs.3.rs-384861/v2
Metadata
- Authors
- Mendez, M. F., Shapira, J. S., McMurtray, A., & Licht, E.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Mendez, Mario F.
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 15
- Issue
- 1
- Pages
- 84-87
- ISSN
- 1064-7481 (ISSN-L)
- OpenAlex
- W2058247742
- Cited by
- 267
- References
- 0
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 9 · 2023: 13 · 2022: 11 · 2021: 23 · 2020: 14 · 2019: 19 · 2018: 13 · 2017: 16 · 2016: 19 · 2015: 6 · 2014: 19 · 2013: 18 · 2012: 11
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG19724-01, P01AG019724)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- donepezil, frontotemporal dementia, acetylcholinesterase inhibitors, behavioral disinhibition, compulsive behavior, adverse drug reactions, cognitive performance
- MeSH terms
- Donepezil, Behavioral Symptoms, Cholinesterase Inhibitors, Compulsive Behavior, Dementia, Female, Humans, Indans, Male, Middle Aged, Piperidines
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