Maintaining
cognitive function in Alzheimer disease:
how effective are current treatments?
Tariot PN
Department of Psychiatry,
University of Rochester Medical Center
New York, USA. Pierre_Tariot@URMC.Rochester.edu
Alzheimer Dis Assoc Disord 2001 Aug;15 Suppl 1:S26-33
ABSTRACT
Cognitive impairment, a core feature of Alzheimer
disease (AD), is highly correlated with functional decline and caregiver
time. Over 12 months, patients with mild-to-moderate AD deteriorate by
5-6 points from baseline on the Alzheimer's Disease Assessment
Scale-cognitive subscale (ADAS-cog). Stabilizing cognitive decline is,
therefore, an important treatment outcome in AD. Cognitive deficits are
thought to result in part from central cholinergic impairment, which
provides the rationale for the enhancement of cholinergic
neurotransmission as a treatment approach for AD. Acetylcholinesterase (AChE)
inhibition has, to date, produced the most promising outcomes in
clinical trials. Galantamine appears to be
novel among marketed agents in that it inhibits AChE and modulates
cholinergic nicotinic receptors, perhaps increasing neurotransmission
via both mechanisms. Long-term effects of AChE inhibitors and galantamine
on ADAS-cog scores of patients with mild-to-moderate AD have been
studied in placebo controlled trials as well as open-extension studies
that followed randomized, double-blind studies for up to 6 months.
Conventional AChE inhibitors (rivastigmine and donepezil) have
maintained ADAS-cog baseline scores for up to 40 weeks in open extension
studies, and Mini-Mental State Examination (MMSE) scores for up to 52
weeks in a placebo-controlled study. The mean ADAS-cog score of galantamine
-treated patients did not change from baseline at 12 months (6 months
double-blind study followed by 6 months open-label extension),
suggesting that cognitive function had been maintained. These results
suggest that cholinergic treatments, including galantamine,
may stabilize cognitive decline of AD patients. This outcome is likely
to make an important difference to patients and caregivers.
