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Denbufylline, a xanthine derivative and PDE4 inhibitor, has effects such as vasodilatation of cerebral vessels (Willette et al., 1997) and potent activation of the hypothalamic–pituitary–adrenal axis. PDE4 is one of the cyclic adenosine monophosphate (cAMP)–specic phosphodiesterases whose tissue distribution is important in pathologies related to the central nervous and immune systems. In experimental animals, denbufylline increases adrenocorticotropic hormone (ACTH), circulating corticosterone, luteinizing hormone, corticotrophin-releasing hormone, and cAMP content of the hypothalamic tissue, but is without effect on arginine vasopressin (Kumari et al., 1997). Treves and Korczyn (1999) studied patients with AD, mixed dementia, and VaD treated with denbufylline. No signicant differences were found in comparison with placebo for the treatment of AD or VaD, although patients who received denbufylline tended to improve their cognitive scores.