Protective effects of NSAIDs on the development of Alzheimer disease

Vlad, Steven C.; Miller, Donald R.; Kowall, Neil W.; Felson, David T.

doi:10.1212/01.wnl.0000311269.57716.63

Cited by 442 publications

(345 citation statements)

References 17 publications

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“…This is consistent with many epidemiological reports that positive effects of NSAIDS when used on for long-term treatment (US Veterans Affairs Health Care System Study (25), Cache County Study (26), Cardiovascular Health Cognition Study (27), Chicago Health and Aging Project (28)). It is also quite interesting to note that in several clinical trials involving patients who already display mild to moderate cognitive decline (Alzheimer Disease Cooperative Study (ADCS) group (29)) NSAIDs showed no benefit.…”

Section: Discussionsupporting

confidence: 91%

Identification of Small Molecule Inhibitors of Neurite Loss Induced by Aβ peptide using High Content Screening

Ofengeim

Shi

Miao

et al. 2012

Journal of Biological Chemistry

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Background: Amyloid-␤-induced degeneration of neurites is a key event in Alzheimer disease. Results: We describe NeuriteIQ high content screening platform for analysis of neurite degeneration. Conclusion: We identified multiple cyclooxygenase inhibitors and agonists of PPAR␥ as suppressors of A␤-induced neurite loss. Significance: Our study demonstrates the feasibility of using NeuriteQ to discover inhibitors of neurite loss and provide a new insight into neurite degeneration.

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Section: Discussionsupporting

confidence: 91%

Identification of Small Molecule Inhibitors of Neurite Loss Induced by Aβ peptide using High Content Screening

Ofengeim

Shi

Miao

et al. 2012

Journal of Biological Chemistry

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“…In observational studies, exposure to NSAID were possibly associated with decreased risk for cognitive decline and AD, depending on class and dose, longer duration or younger age at intake, and APO4 vulnerability (Szekely et al, 2004;Szekely et al, 2008;Vlad et al, 2008;de Craen et al, 2005;Gorelick, 2010;Szekely and Zandi, 2010). Conversely, the three randomized controlled trials performed using rofecoxib, celecoxib and naproxen, suggested an increased risk in AD and no consistent association or worsening of cognitive function with naproxen (in global summary scores and verbal fluency) (Thal et al, 2005;Lyketsos et al, 2007;Martin et al, 2008).…”

Section: Nsaid Use Cognitive Decline and Dementiamentioning

confidence: 99%

Steroid and nonsteroidal anti-inflammatory drugs, cognitive decline, and dementia

Ancelin

Carrière

Helmer

et al. 2012

Neurobiology of Aging

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“…The results of the 8-arm radial maze task indicate that telmisartan alleviated spatial memory impairment in CI+ Aβ-aggregate-treated rats. The ameliorative effect of telmisartan on spatial memory impairment via the reduction of neuronal cell death is indicated from the following findings: reduction of neuronal cell death in the hippocampal CA1 region and improvement of impaired spatial memory in rats with repeated cerebral ischemia (cerebrovascular dementia model) 23) ; lack of improvement in spatial memory impairment in CI+ Aβ-oligomer rats that did not exhibit hippocampal neuronal cell death.…”

Section: Discussionmentioning

confidence: 99%

“…29) Furthermore, the epidemiological survey shows that rheumatic patients who took non-steroidal anti-inflammatory drugs (NSAIDs) for extended periods of time have lower risks of developing AD. 23) Accordingly, telmisartan is expected to reduce the risk of AD owing to its inflammation-suppressing effect. In fact, telmisartan was reported to reduce the expression of TNFα mRNA in mice.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effects of Telmisartan on the Inflammatory Response and Impaired Spatial Memory in a Rat Model of Alzheimer’s Disease Incorporating Additional Cerebrovascular Disease Factors

Shindo

Takasaki

Uchida

et al. 2012

Biological & Pharmaceutical Bulletin

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Telmisartan, an angiotensin type 1 receptor blocker, is used in the management of hypertension to control blood pressure. In addition, telmisartan has a partial agonistic effect on peroxisome proliferator activated receptor γ (PPARγ). Recently, the effects of telmisartan on spatial memory or the inflammatory response were monitored in a mouse model of Alzheimer's disease (AD). However, to date, no studies have investigated the ameliorative effects of telmisartan on impaired spatial memory and the inflammatory response in an AD animal model incorporating additional cerebrovascular disease factors. In this study, we examined the effect of telmisartan on spatial memory impairment and the inflammatory response in a rat model of AD incorporating additional cerebrovascular disease factors. Rats were subjected to cerebral ischemia and an intracerebroventricular injection of oligomeric or aggregated amyloid-β (Aβ). Oral administration of telmisartan (0.3, 1, 3 mg/kg/d) seven days after ischemia and Aβ treatment resulted in better performance in the eight arm radial maze task in a dose-dependent manner. Telmisartan also reduced tumor necrosis factor α mRNA expression in the hippocampal region of rats with impaired spatial memory. These effects of telmisartan were antagonized by GW9662, an antagonist of PPARγ. These results suggest that telmisartan has ameliorative effects on the impairment of spatial memory in a rat model of AD incorporating additional cerebrovascular disease factors via its anti-inflammatory effect. Key words telmisartan; tumor necrosis factor α; Alzheimer disease; inflammatory; ratThe epidemiological survey findings indicate that the Alzheimer's disease (AD) rapidly progresses in case of which elderly people have a history of lifestyle-related diseases such as hypertension, lipid abnormality, diabetes and cerebrovascular disease (e.g., brain infarction). [1][2][3][4][5] The clinical report also indicates that the AD patients with a history of cerebrovascular disease exhibit a more rapid progression of dementia.6) Overall, 47% of demented participants in that clinical study had AD and/or additional brain infarcts, suggesting that the mixed form of such dementia may be very common in the elderly.Based on the context of the above clinical studies, we have developed several AD-like animal models incorporated additional lifestyle-related disease factors, where the model animals in various clinical states were obtained by imposing the altering aggregate morphology of amyloid-β (Aβ) on naïve animals. 7,8) Since theses animal models reveal that administration of aggregated Aβ could induce neuronal cell death and spatial memory impairment, we have used them to evaluate the related-drug efficacy. Our pharmacological study indicates that the hypoxia treatment enhances Aβ-induced apoptosis in cultured hippocampal neurons. 9)

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Protective effects of NSAIDs on the development of Alzheimer disease

Abstract: Long-term nonsteroidal anti-inflammatory drug (NSAID) use was protective against Alzheimer disease. Findings were clearest for ibuprofen. A beta (1-42)-suppressing NSAIDs did not differ from others.

Cited by 442 publications

References 17 publications

Identification of Small Molecule Inhibitors of Neurite Loss Induced by Aβ peptide using High Content Screening

Identification of Small Molecule Inhibitors of Neurite Loss Induced by Aβ peptide using High Content Screening

Steroid and nonsteroidal anti-inflammatory drugs, cognitive decline, and dementia

Ameliorative Effects of Telmisartan on the Inflammatory Response and Impaired Spatial Memory in a Rat Model of Alzheimer’s Disease Incorporating Additional Cerebrovascular Disease Factors

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