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What constitutes clinical evidence for neuroprotection in Alzheimer disease: support for the cholinesterase inhibitors?

Publication ,  Journal Article
Mori, E; Hashimoto, M; Krishnan, KR; Doraiswamy, PM
Published in: Alzheimer Dis Assoc Disord
2006

The progression of Alzheimer disease (AD) corresponds to a prolonged course of neuronal loss in the cerebral cortex. Strategies aimed at reducing the rates of neuronal loss are therefore particularly important. The clinical measures to evaluate the disease-modifying effect of an intervention are readily confounded by any symptomatic benefit of the intervention. Thus, when testing putative neuroprotective agents that are known to have symptomatic effects, it can be difficult to separate the 2 effects. The hypothesis that cholinesterase inhibitors (ChEIs) only treat symptoms caused by cholinergic imbalances in AD is overly simplistic. Evidence has now accumulated that ChEIs have a neuroprotective, disease-modifying property. In this paper, to answer the question of what constitutes clinical evidence for neuroprotection in AD, we have reviewed clinical studies with specific designs, including "delaying end point," "withdrawal," and "randomized start" designs. We have also reviewed data on surrogate biomarkers of disease progression that may indicate a disease-modifying action. In addition, we have reviewed evidence indicating that ChEIs may protect cells in the brain of patients with AD. Among the clinical data suggesting a possible neuroprotective effect of ChEIs, the most rigorous published evidence comes from magnetic resonance imaging (MRI) hippocampal volumetric studies with donepezil.

Duke Scholars

Published In

Alzheimer Dis Assoc Disord

DOI

ISSN

0893-0341

Publication Date

2006

Volume

20

Issue

2 Suppl 1

Start / End Page

S19 / S26

Location

United States

Related Subject Headings

  • Neuroprotective Agents
  • Magnetic Resonance Imaging
  • Humans
  • Hippocampus
  • Geriatrics
  • Clinical Trials as Topic
  • Cholinesterase Inhibitors
  • Brain
  • Atrophy
  • Apoptosis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Mori, E., Hashimoto, M., Krishnan, K. R., & Doraiswamy, P. M. (2006). What constitutes clinical evidence for neuroprotection in Alzheimer disease: support for the cholinesterase inhibitors? Alzheimer Dis Assoc Disord, 20(2 Suppl 1), S19–S26. https://doi.org/10.1097/01.wad.0000213805.66811.31
Mori, Etsuro, Mamoru Hashimoto, K Ranga Krishnan, and P Murali Doraiswamy. “What constitutes clinical evidence for neuroprotection in Alzheimer disease: support for the cholinesterase inhibitors?Alzheimer Dis Assoc Disord 20, no. 2 Suppl 1 (2006): S19–26. https://doi.org/10.1097/01.wad.0000213805.66811.31.
Mori E, Hashimoto M, Krishnan KR, Doraiswamy PM. What constitutes clinical evidence for neuroprotection in Alzheimer disease: support for the cholinesterase inhibitors? Alzheimer Dis Assoc Disord. 2006;20(2 Suppl 1):S19–26.
Mori, Etsuro, et al. “What constitutes clinical evidence for neuroprotection in Alzheimer disease: support for the cholinesterase inhibitors?Alzheimer Dis Assoc Disord, vol. 20, no. 2 Suppl 1, 2006, pp. S19–26. Pubmed, doi:10.1097/01.wad.0000213805.66811.31.
Mori E, Hashimoto M, Krishnan KR, Doraiswamy PM. What constitutes clinical evidence for neuroprotection in Alzheimer disease: support for the cholinesterase inhibitors? Alzheimer Dis Assoc Disord. 2006;20(2 Suppl 1):S19–S26.

Published In

Alzheimer Dis Assoc Disord

DOI

ISSN

0893-0341

Publication Date

2006

Volume

20

Issue

2 Suppl 1

Start / End Page

S19 / S26

Location

United States

Related Subject Headings

  • Neuroprotective Agents
  • Magnetic Resonance Imaging
  • Humans
  • Hippocampus
  • Geriatrics
  • Clinical Trials as Topic
  • Cholinesterase Inhibitors
  • Brain
  • Atrophy
  • Apoptosis