Clinical trial of indomethacin in Alzheimer's disease

Rogers, Jospeh; Kirby, L.; Hempelman, S. R.; Berry, DA; McGeer, Patrick L.; Kaszniak, Alfred W.; Zalinski, J.; Cofield, M.; Mansukhani, L.; Willson, P. D.; Kogan, Frederick J.

doi:10.1212/wnl.43.8.1609

Cited by 950 publications

(439 citation statements)

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“…But these drugs only offer a symptomatic approach and are of limited effect in long term administration. Other drugs have been reported to at least delay the progression of AD, like indomethacin (McGeer and McGeer, 1999;Rogers et al, 1993), selegilin and vitamin E (Sano et al, 1997), suggesting that anti-inflammatory and antioxidant agents can be beneficial in the treatment of AD patients.…”

Section: Discussionmentioning

confidence: 99%

Alpha-lipoic acid as a new treatment option for Azheimer type dementia

Häger¹,

Marahrens²,

Kenklies³

et al. 2001

Archives of Gerontology and Geriatrics

167

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Oxidative stress and energy depletion are characteristic biochemical hallmarks of Alzheimer's disease (AD), thus antioxidants with positive effects on glucose metabolism such as thioctic (a-lipoic) acid should exert positive effects in these patients. Therefore, 600 mg a-lipoic acid was given daily to nine patients with AD and related dementias (receiving a standard treatment with acetylcholinesterase inhibitors) in an open study over an observation period of, on avarage, 337 980 days. The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (mini-mental state examination: MMSE and AD assessment scale, cognitive subscale: ADAScog). Despite the fact that this study was small and not randomized, this is the first indication that treatment with a-lipoic acid might be a successful 'neuroprotective' therapy option for AD and related dementias.

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Section: Discussionmentioning

confidence: 99%

Alpha-lipoic acid as a new treatment option for Azheimer type dementia

Häger¹,

Marahrens²,

Kenklies³

et al. 2001

Archives of Gerontology and Geriatrics

167

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“…All groups involved case-controlled studies except where population based is specified. study in which AD cases given indomethacin maintained their Mini Mental Status for the 6-month period of the trial, whereas those on placebo showed the expected 10-12% loss [50].…”

Section: Epidemiological Evidence That Nsaids May Be Useful In Admentioning

confidence: 99%

Inflammation of the brain in Alzheimer's disease: implications for therapy

McGeer

1999

Journal of Leukocyte Biology

202

117

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We briefly describe the similarities and differences between a systemic and a local immune reaction and review the evidence that the latter occurs in Alzheimer's disease (AD) brains. The evidence comes mainly from studies on the complement system, microglia, and cytokines, all of which are important actors in the inflammatory process. The evidence is now overwhelming that the complement proteins and many of the mediators of inflammation are produced locally by brain cells. We will mention briefly the many epidemiological studies indicating that the use of anti-inflammatory drugs reduces the incidence and slows the progress of AD. Mention will also be made of some recent work on animal models of possible relevance to AD and inflammation. J. Leukoc. Biol. 65: 409-415; 1999.

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“…Ibuprofen possesses preferential Abeta-42 lowering activity not related to the inhibition of cyclooxygenases, but altering gamma-secretase activity (Leuchtenberger et al, 2006;Weggen et al, 2001). Indomethacin, also shown to lower Abeta-42, stabilizes cognitive decline in clinical trials of AD patients, perhaps independently of its Cox-2 inhibitory properties (Rogers et al, 1993;Weggen et al, 2001). Negative studies may have resulted from use of NSAIDs relatively late in the disease process or imprecise targeting of the inflammation response.…”

Section: Inflammation In Neurodegenerative Disordersmentioning

confidence: 99%

Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

Conejero-Goldberg

Davies

Ulloa

2008

Neuroscience & Biobehavioral Reviews

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Alzheimer's disease (AD) is the leading cause of dementia affecting over 25 million people worldwide. Classical studies focused on the description and characterization of the pathological hallmarks found in AD patients including the neurofibrillary tangles and the amyloid plaques. Current strategies focus on the etiology of these hallmarks and the different mechanisms contributing to neurodegeneration. Among them, recent studies reveal the close interplay between the immunological and the neurodegenerative processes. This article examines the implications of the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) as a critical link between inflammation and neurodegeneration in AD. Alpha7nAChRs are not only expressed in neurons but also in Glia cells where they can modulate the immunological responses contributing to AD. Successful therapeutic strategies against AD should consider the connections between inflammation and neurodegeneration. Among them, alpha7nAChR may represent a pharmacological target to control these two mechanisms during the pathogenesis of neurodegenerative and behavioral disorders.

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Clinical trial of indomethacin in Alzheimer's disease

Cited by 950 publications

References 1 publication

Alpha-lipoic acid as a new treatment option for Azheimer type dementia

Alpha-lipoic acid as a new treatment option for Azheimer type dementia

Inflammation of the brain in Alzheimer's disease: implications for therapy

Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration

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