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Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial

BACKGROUND: Dementia greatly contributes to poor prognosis in patients with Parkinson's disease (PD). We previously reported that severe olfactory dysfunction may be a good predictor of Parkinson's disease dementia (PDD). In this trial, we investigated whether early administration of donep...

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Autores principales: Baba, Toru, Takeda, Atsushi, Murakami, Aya, Koga, Tadashi, Isomura, Tatsuya, Mori, Etsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289637/
https://www.ncbi.nlm.nih.gov/pubmed/35860451
http://dx.doi.org/10.1016/j.eclinm.2022.101571
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author Baba, Toru
Takeda, Atsushi
Murakami, Aya
Koga, Tadashi
Isomura, Tatsuya
Mori, Etsuro
author_facet Baba, Toru
Takeda, Atsushi
Murakami, Aya
Koga, Tadashi
Isomura, Tatsuya
Mori, Etsuro
author_sort Baba, Toru
collection PubMed
description BACKGROUND: Dementia greatly contributes to poor prognosis in patients with Parkinson's disease (PD). We previously reported that severe olfactory dysfunction may be a good predictor of Parkinson's disease dementia (PDD). In this trial, we investigated whether early administration of donepezil to patients with severe hyposmia can reduce the development of PDD. METHODS: This was a multi-centre, randomized, double-blind, parallel group, placebo-controlled trial in patients with non-demented PD with severe hyposmia (The Donepezil Application for Severe Hyposmic Parkinson's Disease [DASH-PD] study). A total of 201 patients were randomly allocated to receive donepezil or placebo in addition to standard therapy for PD. Patients were followed up every 6 months until the onset of PDD or for a maximum of 4 years. The primary endpoint was the onset of dementia. The secondary endpoint was cognitive impairment measured by Addenbrooke's Cognitive Examination-Revised (ACE-R) and the Clinical Dementia Rating (CDR). (UMIN000009958: February 2013 to May 2019). FINDINGS: A total of 201 hyposmic patients with PD were randomly assigned to a treatment: 103 to donepezil and 98 to placebo. Overall, 141 (70%) patients completed the 4-year intervention. During follow-up, 7 of 103 (6.8%) patients in the donepezil group and 12 of 98 (12.2%) patients in the placebo group developed PDD; however, the hazard ratio of PDD incidence was not statistically significant (hazard ratio (HR), 0.609; 95% confidence interval, 0.240 to 1.547; p = 0.2969). At week 208, the patients in the donepezil group had better scores on the ACE-R (p < 0.005) and the CDR (p < 0.005) than those taking placebo. INTERPRETATION: Administration of donepezil to PD patients with severe olfactory dysfunction for 4 years did not change the incidence of dementia but had a beneficial effect on neuropsychological function, with good tolerability. FUNDING: The Ministry of Health Labour and Welfare and the Japan Agency for Medical Research and Development provided funding for this study.
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spelling pubmed-92896372022-07-19 Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial Baba, Toru Takeda, Atsushi Murakami, Aya Koga, Tadashi Isomura, Tatsuya Mori, Etsuro eClinicalMedicine Articles BACKGROUND: Dementia greatly contributes to poor prognosis in patients with Parkinson's disease (PD). We previously reported that severe olfactory dysfunction may be a good predictor of Parkinson's disease dementia (PDD). In this trial, we investigated whether early administration of donepezil to patients with severe hyposmia can reduce the development of PDD. METHODS: This was a multi-centre, randomized, double-blind, parallel group, placebo-controlled trial in patients with non-demented PD with severe hyposmia (The Donepezil Application for Severe Hyposmic Parkinson's Disease [DASH-PD] study). A total of 201 patients were randomly allocated to receive donepezil or placebo in addition to standard therapy for PD. Patients were followed up every 6 months until the onset of PDD or for a maximum of 4 years. The primary endpoint was the onset of dementia. The secondary endpoint was cognitive impairment measured by Addenbrooke's Cognitive Examination-Revised (ACE-R) and the Clinical Dementia Rating (CDR). (UMIN000009958: February 2013 to May 2019). FINDINGS: A total of 201 hyposmic patients with PD were randomly assigned to a treatment: 103 to donepezil and 98 to placebo. Overall, 141 (70%) patients completed the 4-year intervention. During follow-up, 7 of 103 (6.8%) patients in the donepezil group and 12 of 98 (12.2%) patients in the placebo group developed PDD; however, the hazard ratio of PDD incidence was not statistically significant (hazard ratio (HR), 0.609; 95% confidence interval, 0.240 to 1.547; p = 0.2969). At week 208, the patients in the donepezil group had better scores on the ACE-R (p < 0.005) and the CDR (p < 0.005) than those taking placebo. INTERPRETATION: Administration of donepezil to PD patients with severe olfactory dysfunction for 4 years did not change the incidence of dementia but had a beneficial effect on neuropsychological function, with good tolerability. FUNDING: The Ministry of Health Labour and Welfare and the Japan Agency for Medical Research and Development provided funding for this study. Elsevier 2022-07-14 /pmc/articles/PMC9289637/ /pubmed/35860451 http://dx.doi.org/10.1016/j.eclinm.2022.101571 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Baba, Toru
Takeda, Atsushi
Murakami, Aya
Koga, Tadashi
Isomura, Tatsuya
Mori, Etsuro
Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial
title Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial
title_full Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial
title_fullStr Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial
title_full_unstemmed Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial
title_short Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial
title_sort effect of donepezil for dementia prevention in parkinson's disease with severe hyposmia (the dash-pd study): a randomized long-term placebo-controlled trial
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289637/
https://www.ncbi.nlm.nih.gov/pubmed/35860451
http://dx.doi.org/10.1016/j.eclinm.2022.101571
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