Early-start vs delayed-start donepezil against cognitive decline in Parkinson disease: a randomized clinical trial. (11th February 2021)

• Record Type: Journal Article
• Authors: Sawada, Hideyuki; Oeda, Tomoko; Kohsaka, Masayuki; Tomita, Satoshi; Umemura, Atsushi; Park, Kwiyoung; Yamamoto, Kenji; Kiyohara, Kosuke
• Is Part Of: Expert opinion on pharmacotherapy. Volume 22:Number 3(2021)
• Page Start: 363
• Page End: 371
• Publication Date: 2021-02-11
• Subjects: Cholinergic inflammatory reflex -- dementia -- apolipoprotein ε4; Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1080/14656566.2020.1814255
• Languages: English
• ISSNs: 1465-6566

Abstract

ABSTRACT: Background: Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). Research design and methods: The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. Results: A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant ( P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group ( P = 0.048). Conclusions: Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.