Linked Life Data

16697488

Source:http://linkedlifedata.com/resource/pubmed/id/16697488

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-3-12
pubmed:abstractText
This review reports correlations between four independent fields related to inflammation and Alzheimer disease: fundamental pathology, epidemiology, transgenic animal studies and clinical trials. Activated microglia, along with a spectrum of inflammatory mediators, have been identified in association with the lesions of Alzheimer disease (AD), suggesting that antiinflammatory agents such as NSAIDs should protect against the disease. In multiple epidemiological investigations testing this hypothesis, a significant risk reduction, or a trend towards such a reduction has been observed in long term as opposed to short term users of traditional NSAIDs. In studies where such NSAIDs have been administered to AD transgenic mice, a dose dependent reduction in pathology was observed. The selective C0X-2 inhibitors were ineffective. Results of clinical investigations have so far been disappointing but have nevertheless correlated with fundamental pathological findings and with transgenic mouse results. Four clinical trials using selective COX-2 inhibitors failed which is in keeping with the animal results and is consistent with pathological findings demonstrating that COX-1 and not COX-2 is the appropriate target in activated human microglia. A low dose trial of the traditional NSAID naproxen also failed, but pilot trials using therapeutically established doses of indomethacin and diclofenac/misoprostol showed promise. Further clinical investigations with relatively high doses of traditional NSAIDs might be warranted, although significant side effects should be anticipated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1558-1497
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
639-47
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies.
pubmed:affiliation
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada. mcgeerpl@interchange.ubc.ca
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't