Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial. (September 2022)

• Record Type: Journal Article
• Authors: Baba, Toru; Takeda, Atsushi; Murakami, Aya; Koga, Tadashi; Isomura, Tatsuya; Mori, Etsuro; Hisanaga, Kinya; Ugawa, Yoshikazu; Hattori, Nobutaka; Murata, Miho; Hasegawa, Kazuko; Sobue, Gen; Ito, Hidefumi; Yabe, Ichiro; Yamamoto, Tatsuya; Iijima, Mutsumi; Orimo, Satoshi; Okuma, Yasuyuki; Tokuda, Takahiko; Sugawara, Masahiro; Maeda, Tetsuya; Suzuki, Yoshihiro; Ishida, Yoshinori; Tanaka, Makoto; Saiki, Hidetsugu; Kashihara, Kenichi
• Is Part Of: EClinicalMedicine. Volume 51(2022)
• Publication Date: 2022-09
• Subjects: Parkinson's disease -- Hyposmia -- Cholinesterase inhibitor -- Dementia -- Prevention; Medicine -- Research -- Periodicals; Medical policy -- Periodicals; Clinical Medicine; Health Policy; Public Health; Medical policy; Medicine -- Research; Periodical; Electronic journals; Periodicals; 613
• DOI: 10.1016/j.eclinm.2022.101571
• Languages: English
• ISSNs: 2589-5370

Abstract

Summary: 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.