Maintaining cognitive function in Alzheimer disease: How effective are current treatments?

Cognitive impairment, a core feature of Alzheimer disease (AD), is highly c orrelated with functional decline and caregiver time. Over 12 months, patie nts with mild-to-moderate AD deteriorate by 5-6 points from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Stabil izing 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 cholinergi c neurotransmission as a treatment approach for AD. Acetylcbolinesterase (A ChE) inhibition has, to date, produced the most promising outcomes in clini cal trials. Galantamine appears to be novel among marketed agents in that i t inhibits AChE and modulates cholinergic nicotinic receptors, perhaps incr easing neurotransmission via both mechanisms. Long-term effects of AChE inh ibitors and galantamine on ADAS-cog scores of patients with mild-to-moderat e AD have been studied in placebo controlled trials as well as open-extensi on studies that followed randomized, double-blind studies for up to 6 month s. Conventional AChE inhibitors (rivastigmine and donepezil) have maintaine d ADAS-cog baseline scores for up to 40 weeks in open extension studies, an d Mini-Mental State Examination (MMSE) scores for up to 52 weeks in a place bo-controlled study. The mean ADAS-cog score of galantamine-treated patient s did not change from baseline at 12 months (6 months double-blind study fo llowed by 6 months open-label extension), suggesting that cognitive functio n had been maintained. These results suggest that cholinergic treatments, i ncluding galantamine, may stabilize cognitive decline of AD patients. This outcome is likely to make an important difference to patients and caregiver s.