Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease

McGeer, Patrick L.; Schulzer, Michael; McGeer, Edith G.

doi:10.1212/wnl.47.2.425

Cited by 1,274 publications

(708 citation statements)

References 14 publications

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“…Earlier, we had reported that sustained use of NSAID might contribute to the development of renal cell carcinoma, and that such exposure might explain approximately 20% of the cases diagnosed in Los Angeles County (Gago-Dominguez et al, 1999). On the other hand, there is growing evidence that NSAID use protects against colorectal cancer, Alzheimer's disease and ischaemic heart disease (Steering Committee of the Physicians' Health Study Research Group, 1989;Giovannucci et al, 1995;McGeer et al, 1996). This study suggests that NSAID use also may protect against another relatively common cancer in the USA as well as worldwide.…”

Section: Discussionmentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

et al. 2000

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Summary Inclusion of phenacetin among 'proven' human carcinogens by the IARC in 1987, raised concerns about the carcinogenic potential of acetaminophen, its major metabolite. Acetaminophen has been implicated as a possible causal agent in the development of cancer of the renal pelvis. The bladder and renal pelvis, which derive from the same embryological structure, share the same transitional type of epithelium. Past studies have been inconclusive on the possible relationship among these analgesics and bladder cancer but no large, highly detailed study of this association has been conducted. A population-based case-control study conducted in Los Angeles, California, involved 1514 incident bladder cancer cases and an equal number of controls who were matched to the index cases by sex, date of birth (within 5 years) and race. Detailed information on medication use and prior medical conditions was collected through in-person interviews. Regular use of analgesics was not associated with an increased risk of bladder cancer in either men or women. In fact, compared with non-or irregular users, regular analgesic users were at a decreased risk of bladder cancer overall (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.96). However, there were clear differences in both the direction and strength of the associations between the different formulation classes of analgesics and bladder cancer risk. Intake of phenacetin was positively related to bladder cancer risk in a dose-dependent manner while intake of its major metabolite in humans, acetaminophen, was unrelated to risk. Intake of all classes of NSAIDs, except pyrazolon derivatives, were negatively associated with bladder cancer risk, with suggestive evidence that the protective effect varies in strength by subcategories of formulation. Acetic acids seemed to exhibit the strongest protective effect, whereas aspirin/other salicylic acids and oxicam showed the weakest protection.

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Section: Discussionmentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

et al. 2000

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“…Recent evidence suggests that inflammatory processes play an active role in AD; epidemiological studies reported that the use of nonsteroidal anti-inflammatory drugs is associated with marked reduction in the risk of AD ( [106,154,156,219,225]). Following this initial observation, additional reports were published that witnessed the involvement of neuroinflammation in AD pathogenesis and progression.…”

Section: Alzheimer's Disease and Neuroinflammationmentioning

confidence: 99%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

278

206

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a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

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“…Neuropathological and epidemiological data suggest that inflammatory mediators and immune mechanisms may play a role in the pathogenesis of Alzheimer's disease (AD) (McGeer et al, 1996;Cagnin et al, 2001;Ho et al, 2001;in 't Veld et al, 2002;Etminan et al, 2003). It has been proposed that these effects may be mediated via the COX-2 enzyme (Pasinetti, 2001).…”

Section: Introductionmentioning

confidence: 99%

A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

Thal

Ferris

Kirby

et al. 2005

Neuropsychopharmacol

371

219

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Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and might be mediated via the COX-2 enzyme. Previous studies with the selective COX-2 inhibitors, rofecoxib and celecoxib, have shown that they do not alter the progression of AD. We conducted a double-blind study to investigate whether rofecoxib could delay a diagnosis of AD in patients with mild cognitive impairment (MCI), a group with an expected annual AD diagnosis rate of 10-15%. MCI patients X65 years were randomized to rofecoxib 25 mg (N ¼ 725) or placebo (N ¼ 732) daily for up to 4 years. The primary end point was the percentage of patients with a clinical diagnosis of AD. The estimated annual AD diagnosis rate was lower than the anticipated 10-15%: 6.4% in the rofecoxib group vs 4.5% in the placebo group (rofecoxib : placebo hazard ratio ¼ 1.46 (95% CI: 1.09, 1.94), p ¼ 0.011). Analyses of secondary end points, including measures of cognition (eg the cognitive subscale of the AD Assessment Scale (ADAS-Cog)) and global function (eg the Clinical Dementia Rating (CDR)), did not demonstrate differences between treatment groups. There was also no consistent evidence that rofecoxib differed from placebo in post hoc analyses comparing ADAS-Cog and CDR-sum of boxes scores in overlapping subgroups of patients who had Mini Mental State Exam scores of 24-26 in the present MCI study and in a previous AD treatment study with a similar design. The results from this MCI study did not support the hypothesis that rofecoxib would delay a diagnosis of AD. In conjunction with the lack of effects observed in previous AD studies, the findings suggest that inhibition of COX-2 is not a useful therapeutic approach in AD.

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Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease

Cited by 1,274 publications

References 14 publications

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment

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