Donepezil Combined with DL-3-n-Butylphthalide Delays Cognitive Decline in Patients with Mild to Moderate Alzheimer’s Disease: A Multicenter, Prospective Cohort Study

Article type: Research Article

Authors: Wang, Jin^a | Guo, Xiaojuan^a | Lu, Wenhui^a | Liu, Jie^a | Zhang, Hong^b | Quan, Qingyun^c | Su, Hang^d | Ma, Li^e | Gao, Fan^f | Qu, Qiumin^{a; *}

Affiliations: [a] Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China | [b] Department of Neurology, Shaanxi Provincial People’s Hospital, Xi’an, China | [c] Department of Gerontology, Shaanxi Provincial Corps Hospital, Chinese People’s Armed Police Forces, Xi’an, China | [d] Department of Neurology, XiDian Group Hospital, Xi’an, China | [e] Department of Gerontology, The Ninth Hospital of Xi’an, Xi’an, China | [f] Clinical Research Central, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Correspondence: [*] Correspondence to: Qiumin Qu, Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, Xi’an 710061, China. Tel./Fax: +86 29 8532 4083; E-mail: [email protected].

Abstract: Background:Vascular factors and mitochondria dysfunction contribute to the pathogenesis of Alzheimer’s disease (AD). DL-3-n-butylphthalide (NBP) has an effect in protecting mitochondria and improving microcirculation. Objective:The aim was to investigate the effect of donepezil combined NBP therapy in patients with mild-moderate AD. Methods:It was a prospective cohort study. 92 mild-moderate AD patients were classified into the donepezil alone group (n = 43) or the donepezil combined NBP group (n = 49) for 48 weeks. All patients were evaluated with Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog), Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC-plus), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI) every 12 weeks. All patients were monitored for adverse events (AEs). The efficacy was analyzed using multivariate logistic regression analysis. Results:The multivariate logistic regression analysis showed that the changes of ADAS-cog score (OR = 2.778, 95% CI: [1.087, 7. 100], p = 0.033) and ADCS-ADL score (OR = 2.733, 95% CI: [1.002, 7.459], p = 0.049) had significant difference between donepezil alone group and donepezil combined NBP group, while the changes of NPI (OR = 1.145, 95% CI: [0.463, 2.829], p = 0.769), MMSE (OR = 1.563, 95% CI: [0.615, 3.971], p = 0.348) and CIBIC-plus (OR = 2.593, 95% CI: [0.696, 9.685], p = 0.156) had no significant difference. The occurrence of AEs was similar in the two groups. Conclusion:Over the 48-week treatment period, donepezil combined NBP group had slower cognitive decline and better activities of daily living in patients with mild to moderate AD. These indicated that the multi-target therapeutic effect of NBP may be a new choice for AD treatment.

Keywords: Alzheimer’s disease, clinical trial, DL–3-n-butylphthalide, drug treatment, prospective cohort study

DOI: 10.3233/JAD-201381

Journal: Journal of Alzheimer's Disease, vol. 80, no. 2, pp. 673-681, 2021