Maintaining cognitive function in Alzheimer disease: how effective are current treatments?
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.
Tariot
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Department of Psychiatry, University of Rochester Medical Center, New York, USA. Pierre_Tariot@URMC.Rochester.edu
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005702:Galantamine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D018697:Nootropic Agents; D005702:Galantamine