Background: The adipokine adiponectin (APN)'s role in Alzheimer's disease (AD) is controversial. Some studies suggest APN is neuroprotective while others propose it has harmful effects. We have used Multiple Indicators Multiple Causes (MIMIC) models to evaluate the effects of serum protein biomarkers on cognitive performance in the Texas Alzheimer's Research and Care Consortium (TARCC) (Royall DR, Bishnoi RJ, Palmer RF. Serum IGF-BP2 strongly moderates age's effect on cognition: a MIMIC analysis. Neurobiol Aging. 2015;36:2232-2240; Bishnoi RJ, Palmer RF, Royall DR. Vitamin D binding protein as a serum biomarker of Alzheimer's disease. J Alzheimers Dis. 2015;43:37-45; Bishnoi RJ, Palmer RF, Royall DR. Serum interleukin (IL)-15 as a biomarker of Alzheimer's disease. PLoS One. 2015;10:e0117282).
Methods: MIMIC models were constructed and replicated in randomly selected 50% splits of TARCC's data (Group 1 N = 1,691; Group 2 N = 1,690) and used to evaluate the relationship between serum APN levels and cognition. Our approach has been to divide general intelligence (Spearman's g) (Spearman C. The Abilities of Man: Their Nature and Measurement. 1932) into two latent variables, δ (ie, a dementia-specific phenotype representing the disabling fraction of cognitive variance) and g prime (g') (ie, the residual non-disabling fraction). Only effects on δ are likely to be dementing.
Results: Serum APN was significantly related to δ scores (r = .10, p = .015). APN had no significant effect on g' (r = -.25, p = .66), nor did it have any independent direct effects on cognitive performance. These results were replicated across random subsets (ΔCHISQ = 2.8(7), p > .90).
Conclusions: APN's effect on cognition is mediated through intelligence (ie, δ), likely to be disabling, and therefore to mediate one or more dementing processes. We have previously shown APN to partially mediate age's-specific effect on δ (Royall DR, Al-Rubaye S, Bishnoi R, Palmer RF. Serum protein mediators of dementia and aging proper. Aging (Albany NY). 2016;8:3241-3254). However, because the current model is age adjusted, APN must mediate one or more additional age-independent dementing process(es), possibly AD.
Keywords: Biomarkers; Cognition; Functional performance; Metabolism.
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