The present invention provides compositions and methods for inhibiting progressive cognitive impairment in persons at risk of developing dementia, for example patients suffering from MCI. It is based, at least in part, on the discovery that nimesulide, at extremely low concentrations, has a number of anti-amyloid effects, including decreasing the level of AbetaSUB40/SUB, inhibiting the activity of secretase-gamma, and favoring the formation of sAPPalpha. As extracellular beta-amyloid accumulation is associated with pathologic cognitive deterioration, nimesulide may be used to intervene in amyloid plaque formation and thereby retard cognitive decline.
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