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Pharmacological strategies for the prevention of Alzheimer's disease.

Publication ,  Journal Article
Doraiswamy, PM; Xiong, GL
Published in: Expert Opin Pharmacother
January 2006

This review examines key pharmacological strategies that have been clinically studied for the primary or secondary prevention of Alzheimer's disease. Much information (neuropsychological, genetic and imaging) is already available to characterise an individual's risk for developing Alzheimer's disease. However, regulatory pathways for obtaining a prevention indication are less well charted, and such trials tend to involve 3- to 7-year studies of 1000 - 5000 individuals, depending on baseline status. Treatments developed for prevention will also need to have superior safety. For these reasons, > 100 proprietary pharmacological products are currently being developed for an Alzheimer's disease treatment, but only a few are being studied for prevention. Randomised trial data are available for antihypertensive agents (calcium channel blockers, angiotensin-converting enzyme inhibitors), pravastatin, simvastatin, conjugated oestrogen, raloxifene, rofecoxib, CX516 (AMPA agonist) and cholinesterase inhibitors regarding efficacy for Alzheimer's disease prevention. At least four large prevention trials of conjugated oestrogen, selenium and vitamin E, Ginkgo biloba and statins are currently underway. Strategies using other agents have not yet been evaluated in Alzheimer's disease prevention clinical trials. These include anti-amyloid antibodies, active immunisation, selective secretase inhibitors and modulators, microtubule stabilisers (e.g., paclitaxel), R-flurbiprofen, xaliproden, ONO-2506, FK962 (somatostatin releaser), SGS 742 (GABA(B) antagonist), TCH 346 (apoptosis inhibitor), Alzhemedtrade mark, phophodiesterase inhibitors, rosiglitazone, leuprolide, interferons, metal-protein attenuating compounds (e.g., PBT2), CX717, rasagaline, huperzine A, antioxidants and memantine. Studies combining lifestyle modification and drug therapy have not been conducted. Full validation of surrogate markers for disease progression (such as amyloid imaging) should further facilitate drug development. Reducing the complexity of prevention trials and gaining regulatory consensus of design is a high priority for the field.

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Published In

Expert Opin Pharmacother

DOI

EISSN

1744-7666

Publication Date

January 2006

Volume

7

Issue

1

Start / End Page

1 / 10

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • Pharmaceutical Preparations
  • Humans
  • Drug Delivery Systems
  • Clioquinol
  • Alzheimer Disease
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Doraiswamy, P. M., & Xiong, G. L. (2006). Pharmacological strategies for the prevention of Alzheimer's disease. Expert Opin Pharmacother, 7(1), 1–10. https://doi.org/10.1517/14656566.7.1.1
Doraiswamy, P Murali, and Glen L. Xiong. “Pharmacological strategies for the prevention of Alzheimer's disease.Expert Opin Pharmacother 7, no. 1 (January 2006): 1–10. https://doi.org/10.1517/14656566.7.1.1.
Doraiswamy PM, Xiong GL. Pharmacological strategies for the prevention of Alzheimer's disease. Expert Opin Pharmacother. 2006 Jan;7(1):1–10.
Doraiswamy, P. Murali, and Glen L. Xiong. “Pharmacological strategies for the prevention of Alzheimer's disease.Expert Opin Pharmacother, vol. 7, no. 1, Jan. 2006, pp. 1–10. Pubmed, doi:10.1517/14656566.7.1.1.
Doraiswamy PM, Xiong GL. Pharmacological strategies for the prevention of Alzheimer's disease. Expert Opin Pharmacother. 2006 Jan;7(1):1–10.

Published In

Expert Opin Pharmacother

DOI

EISSN

1744-7666

Publication Date

January 2006

Volume

7

Issue

1

Start / End Page

1 / 10

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • Pharmaceutical Preparations
  • Humans
  • Drug Delivery Systems
  • Clioquinol
  • Alzheimer Disease
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences