155 Since there was no benefit at 2 to 3 years, these results for donepezil are consistent with a symptomatic effect that lasts for up to 18 months. A similar 2-year trial of galantamine in MCI failed to show

a benefit on the primary end points, but there was some benefit on a secondary cognitive measure.156 Results of a 3- to 4-year conversion trial of rivastigmine have not as yet been reported, but a similar 4-year trial of the anti-inflammatory drug rofecoxib failed to show any clinical efficacy157 Despite the mixed and generally disappointing results of these initial MCI clinical trials, an important general finding is that Inhibitors,research,lifescience,medical when the patients progressed to Regorafenib dementia over the course of the trial, the specific diagnosis was almost always AD. This result provides some validation for the Inhibitors,research,lifescience,medical operational criteria used to select cases with “amnestic/AD type” MCI. Conclusion The concept of MCI in the elderly has evolved over the past 40 years to the point where study of MCI is at the cutting edge of research on the early pathology, early diagnosis, Inhibitors,research,lifescience,medical and early treatment of AD. The broad syndrome of MCI, defined clinically as a state of mild impairment that is intermediate between the decline associated with brain

aging and the clear deficits that occur in dementia, is clearly heterogeneous with respect to outcome and underlying etiology. However, it is apparent that the major MCI subgroup consists of individuals destined to progress to a diagnosis Inhibitors,research,lifescience,medical of AD. As reviewed above, this conclusion is supported by growing number of cross-sectional and longitudinal studies, as well as by studies examining postmortem neuropathology and in vivo neuroimaging and biomarker

correlates of AD. Furthermore, Inhibitors,research,lifescience,medical since it is feasible clinically to operationalize the identification “amnestic” MCI cases who are likely to have very early AD, such individuals have become an important research group for inclusion in clinical trials designed to examine agents that may slow the progression of AD. Although clearly valuable as a research tool, it may be debated whether physicians in clinical practice should consider a diagnosis of MCI for individual patients. Because MCI is a heterogeneous entity comprising a variety of neuropathological and psychiatric disorders, and because dementia is not an inevitable outcome, the over term may carry too little prognostic and diagnostic weight to legitimize its widespread use on a case-by-case basis. Furthermore, the lack of universally agreed upon criteria and the public’s unfamiliarity with the concept could result in increasing uncertainty, anxiety, and misunderstanding. Rather than invoking MCI, patients might be better served if their physicians simply conveyed an opinion regarding the most likely underlying pathological mechanism.