Do extrapyramidal features in Alzheimer patients treated with acetylcholinesterase inhibitors predict disease progression?

The objective of the study is to explore the longitudinal course of patients with Alzheimer's disease (AD) with and without extrapyramidal signs (EPS) taking donepezil. A cohort of 106 community-dwelling patients with probable AD receiving donepezil in Sydney, Australia (n = 52) and Manchester, UK (n = 54) was followed over 12 months. Cognition was measured by the Mini-Mental State Exam (MMSE) and the Alzheimer Disease Assessment Scale - Cognitive test (ADAS-Cog) and function by the Alzheimer Disease Cooperative Study - Activities of Daily Living Scale (ADCS-ADL). A further follow-up at five years was conducted to examine mortality and institutionalisation. At baseline, EPS were correlated with MMSE (r=-0.467, P < 0.01), ADAS-Cog (r=0.485, p < 0.01) and ADCS-ADL (r=-0.526, p < 0.01) scores. Patients with EPS had lower MMSE (F=9.95, df= 1, p=0.002) and ADCS-ADL (F=9.41, df=l, p=0.003) scores than patients without EPS. Over one year no time main effects or time x group interaction effects were observed for either dependent variable. At five years patients with EPS were found to have a hazard of institution or death :2.2 times higher than those without EPS (p = 0.018; 95% Cl: 1.2, 4.4). There was a positive association between EPS and cognitive and functional impairment. However, EPS did not predict more rapid cognitive or functional decline of patients taking donepezil or response to donepezil. The presence of EPS was a risk factor both for institutionalisation and for death.