[P3.208] Cognitive and Functional Decline and their Relationship in Patients with Mild Alzheimer's Disease

Hong Liu-Siefert,1Eric Siemers,1Karen Sundell,1Karen L. Price,1Baoguang Han,1Katherine Selzler,1Joel Raskin,2Richard Mohs1
1Indianapolis, IN, USA, 2Toronto, ON, Canada


OBJECTIVE: This post-hoc analysis assesses the relationship between cognitive and functional impairment in mild Alzheimer's disease (AD) patients participating in 18-month clinical trials.
BACKGROUND: In patients with AD, the relationship between cognitive and functional progression is not fully understood; however, functional decline has been postulated to follow cognitive decline.
DESIGN/METHODS: Data of patients with mild AD (Mini-Mental State Examination score 20 to 26) were pooled from two multicenter, double-blind, Phase 3 studies (EXPEDITION and EXPEDITION2). Patients were randomized to infusions of 400-mg solanezumab (N=654), a monoclonal antibody binding soluble amyloid beta, or placebo (N=660) every 4 weeks for 18 months. Cognitive and functional outcome measures were assessed using the AD Assessment Scale-Cognitive subscale (ADAS-Cog) and the AD Cooperative Study-Activities of Daily Living (ADCS-ADL). Analyses included comparisons among the normalized scales, correlations between outcome measures, and path analyses to model the relationship of treatment effect on cognition and function.
RESULTS: In placebo-treated patients, normalized ADAS-Cog and ADCS-ADL scales showed that cognitive impairment may precede functional impairment. Additionally, the correlation between cognition and function increased over time (Spearman rank correlation = -0.34 at baseline to -0.62 after 18 months, p<0.001 for both). Solanezumab-treated patients exhibited a 34% reduction in cognitive decline (p=0.001) and an 18% reduction in functional decline (p=.045) compared with placebo-treated patients after 18 months. Path analyses demonstrated that 87% of the treatment effect on function was driven by the treatment effect on cognition, with the remaining 13% due to direct treatment effect.
CONCLUSIONS: Findings from this study are consistent with the hypothesis that functional impairment is primarily related to and follows cognitive decline. The increasing correlation between cognition and function over time suggests that as cognition worsens, function is more directly affected. The cognitive treatment effect appeared to explain the majority of the functional treatment effect.
Study Supported by: Eli Lilly and Company
Category - Aging, Dementia, and Cognitive and Behavioral Neurology: Clinical Trials

Tuesday, April 29, 2014 3:00 PM

P3: Poster Session III: Aging, Dementia, and Cognitive and Behavioral Neurology: Clinical Aspects (3:00 PM-6:30 PM)

 

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