Cognitive and functional decline and their relationship in patients with mild Alzheimer's dementia

J Alzheimers Dis. 2015;43(3):949-55. doi: 10.3233/JAD-140792.


Background: In patients with Alzheimer's disease (AD), the relationship between cognitive and functional progression is not fully understood; however, functional decline has been postulated to follow cognitive decline.

Objective: To assess the relationship between cognitive and functional treatment effects in mild AD dementia patients.

Methods: Data of patients with mild AD were pooled from two multicenter, double-blind, Phase 3 studies. Patients were randomized to infusions of 400-mg solanezumab (n = 654), 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), respectively. Analyses included comparisons among normalized scales, correlations between outcome measures, and path analyses to model the relationship of treatment effect on cognition and function.

Results: Normalized ADAS-Cog and ADCS-ADL scales showed cognitive impairment was more evident than functional impairment in mild AD. The correlation between cognition and function increased over time. 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.

Conclusion: Findings from this study are consistent with the hypothesis that functional impairment is primarily driven by and follows cognitive decline in mild AD dementia. The cognitive treatment effect appeared to explain the majority of the functional treatment effect. It is possible that a cognitive treatment effect may be considered as a leading indicator for functional outcomes in an 18-month clinical trial for milder stages of AD.

Trial registration: NCT00904683 NCT00905372.

Keywords: Activities of daily living; Alzheimer's disease; Phase 3; clinical trials; cognition; correlation of data; dementia; solanezumab.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Activities of Daily Living / psychology*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / psychology*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Cognition / drug effects
  • Cognition / physiology*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / psychology*
  • Disease Progression
  • Humans
  • Neuropsychological Tests


  • Antibodies, Monoclonal, Humanized
  • solanezumab

Associated data