Pierre N. Tariot, MD
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Because of the mild symptomatology associated with its earlier stages, Alzheimer’s disease (AD)
is most commonly diagnosed in an intermediate to late stage of progression. Patients with moderate to
severe AD at diagnosis have already experienced appreciable losses in cognition and functioning.
However, such patients may still benefit greatly from the use of antidementia agents such as cholinesterase
inhibitors (ChEIs) and the N-methyl-D-aspartate (NMDA) receptor open-channel antagonist
memantine. Monotherapy regimens involving a ChEI or memantine have been shown to slow the progression
of cognitive symptoms in patients with moderate to severe AD, although memantine is currently
the only agent approved for use in this setting. Furthermore, combination therapy involving
memantine and a ChEI has been shown to yield increased cognitive benefits relative to ChEI monotherapy,
a result that is believed to be attributable to the distinct therapeutic mechanisms associated
with NMDA receptor open-channel antagonists and ChEIs. Nonetheless, recent findings indicate that
the therapeutic effects of these antidementia agents are not limited to cognition. For example, emerging
data highlight the efficacy of ChEIs and memantine, used either alone or in combination, in improving
outcomes related to patient functioning and behavior, 2 domains that may have a great deal of
significance for patients and caregivers. Furthermore, recent clinical trial data suggest that antidementia
agents may significantly delay nursing home placement, a unique endpoint that can be tremendously
distressing to patients with AD and their caregivers. Thus, it is clear that the ChEIs and
memantine provide substantial benefits that extend across the spectrum of symptoms of AD, improving
outcomes for those who are affected, either directly or indirectly, by this debilitating condition.
J Clin Psychiatry 2006;67(suppl 3):15-22
© Copyright 2006 Physicians Postgraduate Press, Inc.