The effects of metrifonate on the cognitive, behavioral, and functional performance of Alzheimer's disease patients. Metrifonate Study Group.
BACKGROUND
The objective of this study was to evaluate the efficacy and safety of metrifonate, a long-acting acetylcholinesterase inhibitor, in patients clinically diagnosed with probable Alzheimer's disease of mild-to-moderate severity.


METHODS
This was a prospective, multicenter, 26-week, double-blind, parallel group study. The 264 randomized patients met diagnostic criteria of the National Institute of Neurological and Communicative Diseases and Stroke and the Alzheimer's Disease and Related Disorders Association for probable Alzheimer's disease. Patients had Mini-Mental State Examination (MMSE) scores of 10-26 and ischemic scores (Rosen modification) of <4. Metrifonate-treated patients received a single 50-mg dose once daily. The efficacy of metrifonate was investigated with respect to 3 symptom domains. Cognitive performance was analyzed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the MMSE. Psychiatric and behavioral disturbances were analyzed using the Neuropsychiatric Inventory (NPI) and the ADAS-Noncognitive subscale (ADAS-Noncog). The ability to perform instrumental and basic activities of daily living was evaluated using the Disability Assessment for Dementia (DAD) scale. Additionally, global state was assessed using the Clinician Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus) scale.


RESULTS
After 26 weeks of metrifonate therapy, a statistically significant benefit of metrifonate was observed in the cognitive performance of Alzheimer's disease patients (ADAS-Cog, t = 2.55, df = 237, p = .012; MMSE, t = 4.60, df = 237, p = .0001). Metrifonate also significantly attenuated the deterioration in activities of daily living of the patients (DAD total score, t = -2.11, df = 233, p = .036) and relieved patients' psychiatric and behavioral disturbances (NPI total score, t = 2.51, df = 233, p = .013). In addition, metrifonate significantly improved the scores for the global state of the patients (CIBIC-Plus, t = 2.07, df = 232, p = .039). Metrifonate was well tolerated; adverse events were predominantly mild in intensity, and no hepatotoxicity was observed.


CONCLUSIONS
In this study, metrifonate was safe and well tolerated. It benefited the cognitive decline, psychiatric and behavioral disturbances, impaired ability to perform instrumental and basic activities of daily living, and global state of patients diagnosed with mild-to-moderate Alzheimer's disease.
Raskind
M A
MA
Department of Veterans Affairs, Northwest Mental Illness Research, Education and Clinical Center, Seattle, Wash, USA.
Cyrus
P A
PA
Ruzicka
B B
BB
Gulanski
B I
BI
D000203:Activities of Daily Living / Q000523:psychology*; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000188:drug therapy*; D018579:Patient Selection; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014236:Trichlorfon / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D002800:Cholinesterase Inhibitors; D014236:Trichlorfon