title: Metrifonate enhances the ability of Alzheimer's disease patients to initiate, organize, and execute instrumental and basic activities of daily living.
abstract: The objective of this analysis was to evaluate comprehensively the efficacy of metrifonate, a long-acting acetylcholinesterase inhibitor, in improving the ability of mild-to-moderate Alzheimer's disease (AD) patients to perform activities of daily living (ADLs). Alzheimer's disease patients with Mini-Mental State Examination scores of 10 to 26 were enrolled in three 26-week trials to receive once-daily placebo (n = 430) or metrifonate 30 to 60 mg (by weight, n = 650) or 60/80 mg (by weight, n = 197). Metrifonate efficacy was assessed using the Disability Assessment for Dementia scale. Data from the three studies were pooled and analyzed retrospectively. The intent-to-treat analysis (last observation carried forward) at 26 weeks demonstrated that metrifonate significantly improved the ability of AD patients to perform ADLs when compared with placebo (30-60 mg dose, delta = 3.03; P = .002; 60/80 mg dose, delta = 5.25; P = .0002). Metrifonate significantly improved the ability of the AD patients to perform instrumental ADLs, those abilities typically lost first during the disease process (30-60 mg dose, delta = 3.88, P = .002; 60/80 mg dose, delta = 5.79, P = .003). Metrifonate also tended to improve, relative to placebo, the ability of AD patients to use three levels of executive skills when performing ADLs: initiation (30-60 mg dose, delta = 3.45, P = .001; 60/80 mg dose, delta = 5.44, P = .003), planning/organization (30-60 mg dose, delta = 4.50, P = .004; 60/80 mg dose, delta = 4.89, P = .014), and effective execution (30-60 mg dose, delta = 1.80, P = .076; 60/80 mg dose, delta = 4.06, P = .030). These results indicate that metrifonate has a beneficial effect on the ADLs in mild-to-moderate AD patients.
authors.affiliation: School of Physical and Occupational Therapy, McGill University, Montreal, Quebec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Gélinas
authors.forename: S
authors.initials: S
authors.lastname: Gauthier
authors.forename: P A
authors.initials: PA
authors.lastname: Cyrus
mesh_terms: D000203:Activities of Daily Living / Q000523:psychology; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D011446:Prospective Studies; D016896:Treatment Outcome; D014236:Trichlorfon / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D002800:Cholinesterase Inhibitors; D014236:Trichlorfon