Correlation between Cognition and Function across the Spectrum of Alzheimer's Disease
- PMID: 29205252
- DOI: 10.14283/jpad.2016.99
Correlation between Cognition and Function across the Spectrum of Alzheimer's Disease
Abstract
Background: Both cognitive and functional deterioration are characteristic of the clinical progression of Alzheimer's disease (AD).
Objectives: To systematically assess correlations between widely used measures of cognition and function across the spectrum of AD.
Design: Spearman rank correlations were calculated for cognitive and functional measures across datasets from various AD patient populations.
Setting: Post-hoc analysis from existing databases.
Participants: Pooled data from placebo-treated patients with mild (MMSE score ≥20 and ≤26) and moderate (MMSE score ≥16 and ≤19) AD dementia from two Phase 3 solanezumab (EXPEDITION/2) and two semagecesatat (IDENTITY/2) studies and normal, late mild cognitive impairment (LMCI) and mild AD patients from the Alzheimer's Disease Neuroimaging Initiative 2-Grand Opportunity (ADNI-2/GO). Intervention (if any): Placebo (EXPEDITION/2 and IDENTITY/2 subjects).
Measurements: Cognitive and functional abilities were measured in all datasets. Data were collected at baseline and every three months for 18 months in EXPEDITION and IDENTITY studies; and at baseline, 6, 12, and 24 months in the ADNI dataset.
Results: The relationship of cognition and function became stronger over time as AD patients progressed from preclinical to moderate dementia disease stages, with the magnitude of correlations dependent on disease stage and the complexity of functional task. The correlations were minimal in the normal control population, but became stronger with disease progression.
Conclusions: This analysis found that measures of cognition and function become more strongly correlated with disease progression from preclinical to moderate dementia across multiple datasets. These findings improve the understanding of the relationship between cognitive and functional clinical measures during the course of AD progression and how cognition and function measures relate to each other in AD clinical trials.
Keywords: Alzheimer’s diseases; Cognition; correlation; function.
Conflict of interest statement
Drs. Liu-Seifert, Siemers, Selzler, Raskin, and Ms. Sundell are employees and minor shareowners of Eli Lilly and Company. Dr. Aisen serves on a scientific advisory board for NeuroPhage; has served as a consultant to Elan, Wyeth, Eisai, Schering-Plough, Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck, Roche, Amgen, Genentech, Abbott, Pfizer, Novartis, Bayer, Astellas, Dainippon, Biomarin, Solvay, Otsuka, Daiichi, AstraZeneca, Janssen, Medivation, Ichor, Toyama, Lundbeck, Biogen Idec, iPerian, Probiodrug, Somaxon, Biotie, Cardeus, Anavex, Kyowa Hakko Kirin Pharma, Medtronic; and receives research support from Eli Lilly and Baxter, and the NIH [NIA U01-AG10483 (PI), NIA U01-AG024904 (Coordinating Center Director), NIA R01-AG030048 (PI), and R01-AG16381 (Co-I)]. Dr. Cummings has provided consultation to Acadia, ADAMAS, Anavex, Avanir, Baxter, Boehinger-Ingelheim, Bristol-Myers Squibb, Eisai, EnVivo, Genentech, GE Healthcare, GlaxoSmithKline, Lilly, Lundbeck, Medavante, Merck, Novartis, Otsuka, Pfizer, Prana, QR Pharma, Resverlogix, Roche, Sonexa, Suven, Takeda, and Toyoma. Dr. Mohs is a minor shareholder and a retired employee of Eli Lilly and Company.