Vol 6 n° 4 - Mild Cognitive Impairment
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here is great interest in mild cognitive impair- ment (MCI) as an intermediate state between normal aging and dementia. In its broadest sense, the term MCI encompasses a number of causes of cognitive decline, each with their own symptomatic treatment (Table I). This list is not exhaustive, but includes the most common causes of consultation in memory clinics for cognitive decline over age 50: MCI of dysthymic, vascular, and amnestic etiologies.1 This article will focus on the phar- macotherapy of the amnestic type of MCI because of the associated high risk of conversion to Alzheimer’s disease (AD) and the availability of randomized clinical trials (RCTs) studying the safety and efficacy of a number of medications, over  periods  ranging  from  6  months  to 4 years. What is amnestic MCI? Amnestic MCI was defined by Petersen et al2 in the con- text of a natural observation study, which demonstrated a rate of conversion to AD that was well above the inci- dence of age-matched populations. The original amnes- tic MCI criteria are as follows2: • Memory  complaint, preferably  corroborated  by  an informant. • Memory impairment relative to age- and education- matched normal subjects. • Relatively normal general cognitive function. • Largely intact activities of daily living (ADL). • Not demented. A more recent subclassification of MCI has been pro- posed by Petersen3 on the basis of findings from cogni- tive testing in larger number of subjects: • Amnestic or single-memory MCI. • Multiple-domain MCI. • Single non–memory-domain MCI. The first two groups (single-memory MCI and multiple- domain [including memory] MCI) seem to share the 3 9 1 P h a r m a c o l o g i c a l   a s p e c t s T Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org Pharmacotherapy of mild cognitive impairment Serge Gauthier, MD, FRCPC Amnestic mild cognitive impairment (MCI) can be consid- ered as a state with a high risk of developing Alzheimer’s disease within 5 years, or as a prodromal stage of this con- dition. Randomized clinical trials comparing the acetyl- cholinesterase  inhibitor  donepezil  with  placebo  have shown some symptomatic benefit on (i) cognition in one short-term (6-month) study; and (ii) conversion to demen- tia in one long-term (3-year) study, but not for the full duration   of   the   study,   except   in   subjects   with   the apolipoprotein E4 (APOE-4) mutation, in whom the ben- efit was sustained throughout the 3 years. Results from studies on galantamine are still being analyzed; and a rivastigmine study will close in the fall of 2004. It is pre- mature to recommend that acetylcholinesterase inhibitors be used systematically in amnestic MCI. However, impor- tant lessons have been learned from studies in this pro- dromal stage of AD, allowing the testing of hypotheses for disease modification.   © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:391-395. Keywords:  mild  cognitive  impairment;  amnestic  subtype;  clinical  trial;
 acetylcholinesterase inhibitor Author affiliations:  Director, Alzheimer Disease Research Unit, McGill Centre for Studies in Aging, Montreal, Canada Address for correspondence:  McGill Centre for Studies in Aging, 6825 LaSalle Blvd, Verdun (Montreal), Quebec, Canada H4H 1R3 (e-mail: serge.gauthier@mcgill.ca)