Protective effects of NSAIDs on the development of Alzheimer disease

Boston University School of Medicine, Clinical Epidemiology Research and Training Unit, 650 Albany St., Suite X200, Boston, MA 02118, USA.
Neurology (Impact Factor: 8.3). 05/2008; 70(19):1672-7. DOI: 10.1212/01.wnl.0000311269.57716.63
Source: PubMed

ABSTRACT Nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD), but observational studies and trials have offered contradictory results. Prior studies have also been relatively short and small. We examined the effects on AD risk of NSAID use for >5 years and of NSAIDs that suppress formation of A beta (1-42) amyloid in a large health care database.
Cases were veterans aged 55 years and older with incident AD using the US Veterans Affairs Health Care system. Matched controls were drawn from the same population. NSAID exposure was categorized into seven time periods: no use, <or=1 year, >1 but <or=2 years, and so on. Using conditional logistic regression, adjusted for race and comorbidities, we tested the association between AD development and the use of 1) any NSAID, 2) any NSAID excluding nonacetylated salicylates, 3) each NSAID class, 4) each individual NSAID, and 5) A beta (1-42)-suppressing NSAIDs.
We identified 49,349 cases and 196,850 controls. Compared with no NSAID use, the adjusted odds ratios for AD among NSAID users decreased from 0.98 for <or=1 year of use (95% CI 0.95-1.00) to 0.76 for >5 years of use (0.68-0.85). For users of ibuprofen, it decreased from 1.03 (1.00-1.06) to 0.56 (0.42-0.75). Effects of other NSAID classes and individual NSAIDs were inconsistent. There was no difference between a group of A beta (1-42)-suppressing NSAIDs and others. Discussion: 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.

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    • "Aging has been associated with an increasing neuroinflammatory process (Richwine et al., 2005; Ye and Johnson, 1999), and systemic inflammation may be associated with several pathologies, such as, coronary heart disease, diabetes, multiple sclerosis, Alzheimer's disease, and Parkinson's disease (Fito et al., 2007). However, anti-inflammatory therapies have shown mixed and discouraging results (Imbimbo et al., 2010; In t' Veld et al., 2001; Stewart et al., 1997; Vlad et al., 2008). Dietary strategies visibly influence inflammation, as related through both observational studies and controlled feeding trials in which subjects had limited food consumption (Giugliano et al., 2006; Harvie et al., 2011; Johnson et al., 2007; Mozaffarian et al., 2009). "
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    Neurobiology of aging 02/2015; 36(5). DOI:10.1016/j.neurobiolaging.2015.02.020 · 4.85 Impact Factor
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    • "There is much evidence that inflammation can accelerate neuronal cell death ongoing in AD; however it is also associated with amyloid removal by microglia and so modulation of inflammation has to be a balanced approach (Chakrabarty et al., 2010a, 2010b). To date, clinical trials of anti-inflammatory agents for treating AD have not proven to have significant disease-slowing effects, but epidemiological data suggest that long-term manipulation of inflammation may be neuroprotective (Szekely and Zandi, 2010; Vlad et al., 2008). "
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    Neurobiology of Aging 10/2014; 36(2). DOI:10.1016/j.neurobiolaging.2014.09.023 · 4.85 Impact Factor
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    • "Further evidence was provided by several population-based cohorts and case-control studies that revealed a decreased risk for AD when comparing (long-term) NSAID-users to non-users [94] [95] [96] [97] [98] [99]. However, when examined in humans based on medical records or self-reports of NSAID use, NSAID-based γ-secretase modulators (Aβ-lowering drugs) such as ibuprofen, indomethacin or sulindac sulphide were not shown to be advantageous over normal NSAIDs [100] [101]. "
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