Metrifonate treatment of AD influence of APOE genotype

Martin Farlow, P. A. Cyrus, A. Nadel, Debomoy Lahiri, A. Brashear, B. Gulanski

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Objective: To investigate whether an interaction exists between APOE genotype and the response of AD patients to metrifonate treatment and whether APOE genotype independently affects the rate of AID progression. Background: Metrifonate is a new acetylcholinesterase inhibitor for the treatment of AD symptoms. Methods: Data were pooled from four prospective, randomized, double-blind, placebo-controlled clinical trials and analyzed retrospectively. A total of 959 patients who received once-daily placebo (n = 374) or metrifonate (30 to 60 mg based on weight or a 50-mg fixed dose, n = 585) for up to 26 weeks agreed to APOE genotyping. Results: Metrifonate clearly improved the cognitive performance of the AD patients when compared with placebo (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS- Cog], p = 0.0001). The interaction of APOE genotype and the metrifonate effect on cognitive performance were not significant (p = 0.25). Metrifonate also clearly improved the global function of the AD patients when compared with placebo (Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus], p = 0.0001). The interaction of APOE genotype with the metrifonate effect on global function also was not significant (p = 0.70). No significant three-way interactions were observed among APOE genotype, gender, and response to metrifonate treatment (AI)AS-Cog, p = 0.68; CIBIC-Plus, p = 0.26). APOE genotype did not influence disease progression as evaluated by either cognitive performance (ADAS-Cog, p = 0.93) or global function (CIBIC- Plus, p = 0.64). Conclusions: The findings from these studies of up to 26 weeks' duration do not clearly support an interaction between APOE genotype and metrifonate treatment effects. They suggest that APOE genotypes do not necessarily predict an AD patient's response to metrifonate treatment and that APOE genotype may not influence the rate of disease progression for patients with mild to moderate AD.

Original languageEnglish
Pages (from-to)2010-2016
Number of pages7
JournalNeurology
Volume53
Issue number9
StatePublished - Dec 10 1999

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Trichlorfon
Genotype
Placebos
Therapeutics
Disease Progression
Cholinesterase Inhibitors
Controlled Clinical Trials
Caregivers
Alzheimer Disease

Keywords

  • Acetylcholinesterase inhibitor
  • APOE genotype
  • Clinical trial
  • Cognition
  • Dementia
  • Global function

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Farlow, M., Cyrus, P. A., Nadel, A., Lahiri, D., Brashear, A., & Gulanski, B. (1999). Metrifonate treatment of AD influence of APOE genotype. Neurology, 53(9), 2010-2016.

Metrifonate treatment of AD influence of APOE genotype. / Farlow, Martin; Cyrus, P. A.; Nadel, A.; Lahiri, Debomoy; Brashear, A.; Gulanski, B.

In: Neurology, Vol. 53, No. 9, 10.12.1999, p. 2010-2016.

Research output: Contribution to journalArticle

Farlow, M, Cyrus, PA, Nadel, A, Lahiri, D, Brashear, A & Gulanski, B 1999, 'Metrifonate treatment of AD influence of APOE genotype', Neurology, vol. 53, no. 9, pp. 2010-2016.
Farlow M, Cyrus PA, Nadel A, Lahiri D, Brashear A, Gulanski B. Metrifonate treatment of AD influence of APOE genotype. Neurology. 1999 Dec 10;53(9):2010-2016.
Farlow, Martin ; Cyrus, P. A. ; Nadel, A. ; Lahiri, Debomoy ; Brashear, A. ; Gulanski, B. / Metrifonate treatment of AD influence of APOE genotype. In: Neurology. 1999 ; Vol. 53, No. 9. pp. 2010-2016.
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AU - Gulanski, B.

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N2 - Objective: To investigate whether an interaction exists between APOE genotype and the response of AD patients to metrifonate treatment and whether APOE genotype independently affects the rate of AID progression. Background: Metrifonate is a new acetylcholinesterase inhibitor for the treatment of AD symptoms. Methods: Data were pooled from four prospective, randomized, double-blind, placebo-controlled clinical trials and analyzed retrospectively. A total of 959 patients who received once-daily placebo (n = 374) or metrifonate (30 to 60 mg based on weight or a 50-mg fixed dose, n = 585) for up to 26 weeks agreed to APOE genotyping. Results: Metrifonate clearly improved the cognitive performance of the AD patients when compared with placebo (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS- Cog], p = 0.0001). The interaction of APOE genotype and the metrifonate effect on cognitive performance were not significant (p = 0.25). Metrifonate also clearly improved the global function of the AD patients when compared with placebo (Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus], p = 0.0001). The interaction of APOE genotype with the metrifonate effect on global function also was not significant (p = 0.70). No significant three-way interactions were observed among APOE genotype, gender, and response to metrifonate treatment (AI)AS-Cog, p = 0.68; CIBIC-Plus, p = 0.26). APOE genotype did not influence disease progression as evaluated by either cognitive performance (ADAS-Cog, p = 0.93) or global function (CIBIC- Plus, p = 0.64). Conclusions: The findings from these studies of up to 26 weeks' duration do not clearly support an interaction between APOE genotype and metrifonate treatment effects. They suggest that APOE genotypes do not necessarily predict an AD patient's response to metrifonate treatment and that APOE genotype may not influence the rate of disease progression for patients with mild to moderate AD.

AB - Objective: To investigate whether an interaction exists between APOE genotype and the response of AD patients to metrifonate treatment and whether APOE genotype independently affects the rate of AID progression. Background: Metrifonate is a new acetylcholinesterase inhibitor for the treatment of AD symptoms. Methods: Data were pooled from four prospective, randomized, double-blind, placebo-controlled clinical trials and analyzed retrospectively. A total of 959 patients who received once-daily placebo (n = 374) or metrifonate (30 to 60 mg based on weight or a 50-mg fixed dose, n = 585) for up to 26 weeks agreed to APOE genotyping. Results: Metrifonate clearly improved the cognitive performance of the AD patients when compared with placebo (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS- Cog], p = 0.0001). The interaction of APOE genotype and the metrifonate effect on cognitive performance were not significant (p = 0.25). Metrifonate also clearly improved the global function of the AD patients when compared with placebo (Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus], p = 0.0001). The interaction of APOE genotype with the metrifonate effect on global function also was not significant (p = 0.70). No significant three-way interactions were observed among APOE genotype, gender, and response to metrifonate treatment (AI)AS-Cog, p = 0.68; CIBIC-Plus, p = 0.26). APOE genotype did not influence disease progression as evaluated by either cognitive performance (ADAS-Cog, p = 0.93) or global function (CIBIC- Plus, p = 0.64). Conclusions: The findings from these studies of up to 26 weeks' duration do not clearly support an interaction between APOE genotype and metrifonate treatment effects. They suggest that APOE genotypes do not necessarily predict an AD patient's response to metrifonate treatment and that APOE genotype may not influence the rate of disease progression for patients with mild to moderate AD.

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