Plasma Concentration of Donepezil to the Therapeutic Response of Alzheimer's Disease in Taiwanese

Article type: Research Article

Authors: Yang, Yuan-Han^{a; b; d; 1} | Wu, Shey-Lin^{e; f; g; 1} | Chou, Mei-Chuan^d | Lai, Chiou-Lian^{a; d} | Chen, Su-Hwei^c | Liu, Ching-Kuan^{a; b; h; *}

Affiliations: [a] Department of and Master's Program in Neurology, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan | [b] Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan | [c] Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan | [d] Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan | [e] Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan | [f] Department of Bioindustry Technology, Dayeh University, Changhua, Taiwan | [g] Center of General Education Central Taiwan, University of Science and Technology, Taiwan | [h] Department of Neurology, Kaohsiung Municipal, Hsiaokang Hospital, Kaohsiung City, Taiwan

Correspondence: [*] Correspondence to: Ching-Kuan Liu MD, PhD, No. 100, Tzyou 1 Rd, Kaohsiung City, Taiwan. Tel.: +88673121101 6760; Fax: +88673162158; Email: ckliu@kmu.edu.tw.

Note: [1] These authors contributed equally to the manuscript.

Abstract: Donepezil has been approved for the treatment for mild-to-moderate Alzheimer's disease (AD), but the therapeutic response rate varies from 20 to 60%. A higher oral dosage was suggested to have a better therapeutic response in reported results, but the plasma concentration of donepezil was not examined with respect to the therapeutic outcomes in those studies. Therefore, we analyzed the therapeutic responses, measured by neuropsychological assessments, among 70 newly diagnosed AD patients taking donepezil (5 mg daily) in relation to their plasma concentration of donepezil, apolipoprotein E genotype, and demographic characteristics. Our results have showed 60% of recruited AD patients improved in cognition, measured by Mini-Mental Status Examination (MMSE), and 57.1% in global status, by Clinical Dementia Rating Scale (CDR) sum of boxes (CDR-SB). In cognition, compared to the improving group, the clinically worsening group had a significantly higher donepezil concentration [p = 0.022, odds ratio (OR) = 1.024, 95% CI = 1.003–1.045] and higher initial MMSE score (p = 0.007, OR = 1.330, 95% CI = 1.080–1.639). In global status, initially higher CDR-SB (p = 0.028, OR = 2.318, 95% CI = 1.096–4.903) and initially higher MMSE (p = 0.036, OR = 1.201, 95% CI = 1.012–1.425), not donepezil concentration (p = 0.883), were significantly associated with clinical worsening. Our results have indicated that the dosage of donepezil should be reconsidered for AD patients, especially those clinically worsening in cognition.

Keywords: Alzheimer's disease, Clinical Dementia Rating Scale sum of boxes, donepezil, Mini-Mental Status Examination, Taiwanese

DOI: 10.3233/JAD-2010-100936

Journal: Journal of Alzheimer's Disease, vol. 23, no. 3, pp. 391-397, 2011