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. 2015 May;29(3):368-81.
doi: 10.1037/neu0000133. Epub 2014 Sep 15.

Alzheimer disease biomarkers, attentional control, and semantic memory retrieval: Synergistic and mediational effects of biomarkers on a sensitive cognitive measure in non-demented older adults

Andrew J Aschenbrenner  1 , David A Balota  1 , Chi-Shing Tse  2 , Anne M Fagan  3 , David M Holtzman  3 , Tammie L S Benzinger  4 , John C Morris  3
Affiliations

Alzheimer disease biomarkers, attentional control, and semantic memory retrieval: Synergistic and mediational effects of biomarkers on a sensitive cognitive measure in non-demented older adults

Andrew J Aschenbrenner et al. Neuropsychology. 2015 May.

Abstract

Objective: Past studies have shown that measures of attentional control and semantic memory are sensitive markers of Alzheimer's disease (AD). The effects of established biomarkers of AD (cerebrospinal fluid tau and amyloid-beta42, positron emission tomography Pittsburgh compound-B, and apolipoprotein E [APOE] genotype) on concurrent cognitive performance in cognitively normal individuals have been mixed. The present study examined the utility of combining attentional control with semantic retrieval as a sensitive correlate of AD biomarkers and used mediation analyses to examine possible mechanisms by which the biomarkers influence cognition.

Method: Three hundred sixty-three participants completed a category verification task (CVT), and 113 of them concurrently underwent biomarker assessments. On each trial, participants viewed a category (e.g., "unit of time") and verified whether a subsequent target item was an exemplar of the category ("hour") or not ("clock"). Importantly, the nonmembers of the category were associatively related to the category (e.g., "clock" is not "a unit of time," but is highly related), and demanded attentional control to reject.

Results: Accuracy to the foil items was the strongest discriminator between healthy aging and very mild symptomatic AD. Cerebrospinal fluid biomarkers had independent yet synergistic influence on CVT performance in cognitively healthy older adults. Furthermore, the influence of the biomarkers and APOE genotype was mediated primarily through increased levels of PIB.

Conclusion: The combined influence of attentional control with semantic retrieval is a marker of symptomatic AD and a sensitive correlate of established biomarkers for AD risk in cognitively healthy participants. The biomarkers influenced cognition primarily through increased levels of amyloid in the brain.

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Figures

Figure 1
Figure 1
Mean RTs as a function of group and condition. Error bars represent the standard error of the mean.
Figure 2
Figure 2
Mean z-scored RTs as a function of group and condition. Error bars represent the standard error of the mean.
Figure 3
Figure 3
Mean percent correct as a function of group and condition. Error bars represent the standard error of the mean.
Figure 4
Figure 4
Standardized residual plots relating CVT accuracy to the biomarkers after controlling for age and education.
Figure 5
Figure 5
Interaction between CSF tau and Aβ42 as related to associate accuracy. Lines represent simple slopes of AB42 at tertiles of tau.
Figure 6
Figure 6
Final model depicting the relationships between AD biomarkers and CVT performance * p < .05 ** p < .01
Figure 7
Figure 7
Model showing the relationship of APOE on CVT performance is mediated by Aβ42 and PIB. * p < .05 ** p < .01
See this image and copyright information in PMC

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