Failure to Recover from Proactive Semantic Interference Differentiates Amnestic Mild Cognitive Impairment and PreMCI from Normal Aging after Adjusting for Initial Learning Ability

Abstract

Background: There is increasing evidence that the failure to recover from proactive semantic interference (frPSI) may be an early cognitive marker of preclinical Alzheimer's disease (AD). However, it is unclear whether frPSI effects reflect deficiencies in an individual's initial learning capacity versus the actual inability to learn new semantically related targets. Objective: The current study was designed to adjust for learning capacity and then to examine the extent to which frPSI, proactive semantic interference (PSI) and retroactive semantic interference (RSI) effects could differentiate between older adults who were cognitively normal (CN), and those diagnosed with either Pre-Mild Cognitive Impairment (PreMCI) or amnestic MCI (aMCI). Methods: We employed the LASSI-L cognitive stress test to examine frPSI, PSI and RSI effects while simultaneously controlling for the participant's initial learning capacity among 50 CN, 35 aMCI, and 16 PreMCI participants who received an extensive diagnostic work-up. Results: aMCI and PreMCI participants showed greater frPSI deficits (50% and 43.8% respectively) compared to only 14% of CNparticipants. PSI effects were observed for aMCI but not PreMCI participants relative to their CN counterparts. RSI failed to differentiate between any of the study groups. Conclusion: By using participants as their own controls and adjusting for overall learning and memory, it is clear that frPSI deficits occur with much greater frequency in individuals at higher risk for Alzheimer's disease (AD), and likely reflect a failure of brain compen-How to cite this paper:

Vulnerability to semantic and phonological interference in normal aging and amnestic mild cognitive impairment (aMCI).

“…Our results differ from those reported in previous studies using the LASSI-L (E. Crocco et al, 2014; R. E. Curiel et al, 2018), which showed a greater vulnerability to semantic proactive interference and a higher failure to recover from semantic PI in aMCIs compared to older controls.…”

“…Taken together, these studies suggest that the vulnerability to semantic interference observed in aMCI by Lowenstein and colleagues (R. E. Curiel, Crocco, Acevedo, et al, 2013;R. Curiel, Crocco, Czaja, et al, 2013;E. A. Crocco et al, 2018;Snitz et al, 2010) may be explained, at least in part, by executive weaknesses (e.g., inhibitory and monitoring process) above and beyond semantic deficits.…”

“…We performed a mixed ANOVA (2 × 2) on the memory scores (number of words correctly recalled in every trial) and percentage of intrusion errors, using the group (two levels: NC, aMCI) as the between-group factor and the condition (two levels: semantic, phonological) as withinsubjects factor. In addition, we performed a mixed analysis of covariance (ANCOVA; 2 × 2) on the interference score ratios using the group (two levels: NC, aMCI) as the between-group factor and the condition (two levels: semantic, phonological) as within-subjects factor, this time controlling for the initial learning capacity (performance on List A recall) to isolate the vulnerability to interference effect (as in R. E. Curiel et al, 2018). Finally, we also performed ROC (receiver operating characteristic) curves analysis for discriminating between groups on all variables of both tests (semantic and phonological).…”

“…This test also distinguished individuals with subjective cognitive decline (SCD) who will further progress to aMCI from those who will revert to normal on longitudinal follow-up (E. A. E. A. Crocco et al, 2018;D.…”

A review of novel Cognitive Challenge Tests for the assessment of preclinical Alzheimer’s disease.

“…A number of studies employing the LASSI-L have confirmed the unique importance of frPSI in differentiating between aMCI and normal control groups, even after adjusting for initial learning (Crocco et al, 2014;Curiel et al, 2013Curiel et al, , 2018Loewenstein et al, 2021). There are intriguing results across a wide variety of studies conducted both nationally and internationally on frPSI that is uniquely assessed by the LASSI-L.…”