To treat or not to treat?
This is the question in the mild cognitive impairment

Dementia News 78, December 2007

The November issue of PloS Medicine, an open-access source, reports an interesting article by Raschetti et al. dealing with the problem of MCI diagnosis and treatment. MCI refers to a conditions at the fuzzy border normal aging and dementia. In spite of the uncertainties about the clinical diagnosis of MCI, trials have been done in the attempt to study the role of acetylcholinesterase inhibitors in order to assess their effects on the mild cognitive symptoms of MCI and on the progression of MCI to AD. The article reviews and analyzes published and unpublished randomized clinical trials (RCTs) conducted on subjects who had received a diagnosis of MCI and/or abnormal memory function documented by a neuropsychological assessment. All studies were required to have as an outcome measure the time to development of dementia or of possible or probable AD, or the improvement of measurement concerning cognitive/clinical/neuropsychiatric domains, and/or improvements based on neuroimaging examinations The information extracted by the authors included several parameters such as: doses of medication; duration of the trial; number, age, and gender of participants; primary and secondary outcomes; adverse events and deaths occurring during the study period. Of the 157 potentially relevant citations only 8 RCTs satisfied the inclusion criteria, 3 published and 5 unpublished, totalling some 4100 patients, roughly equally divided between active treatment (donepezil, galantamine, rivastigmine) and placebo.

On the basis of their analisys the authors conclude that the use of AChEIs in MCI patients, for periods ranging from few months up to 3 years, was not associated with delay in the onset of AD or dementia. Furthermore, among the various surrogate measures used in the trials, only neuroimaging showed a significant difference in favour of the drug being studied; the clinical implications of this finding are unclear. In addition, the analyzed data showed that the risks associated with ChEIs were not negligible. As the authors comment, MCI seems to be a clinical entity still too heterogeneous and unpredictable underscoring the need of additional research for clearly defining MCI before testing new pharmacological treatments.

As the editor’s summary concludes in pragmatic manner: “Thus, further clinical trials are needed to clarify whether cholinesterase inhibitors can delay the progression of MCI to dementia, but these additional trials should not be done until the diagnosis of MCI has been standardized”. From the point of view of the biologist the analysis reported in this paper underscores the need of the search of biological markers for MCI and a better definition of the biological events associated with the very early stage of Alzheimer disease.


prof. Stefano Govoni
Department of Experimental and Applied Pharmacology, University of Pavia, Italy

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