Amnestic Mild Cognitive Impairment is Characterized by the Inability to Recover from Proactive Semantic Interference across Multiple Learning Trials



Difficulties in inhibition and self-monitoring are early features of incipient Alzheimer’s disease and may manifest as susceptibility to proactive semantic interference. However, due to limitations of traditional memory assessment paradigms, recovery from interference effects following repeated learning opportunities has not been explored. OBJECTIVE: This study employed a novel computerized list learning test consisting of repeated learning trials to assess recovery from proactive and retroactive semantic interference. DESIGN: The design was cross-sectional.


Participants were recruited from the community as part of a longitudinal study on normal and abnormal aging. Participants: The sample consisted of 46 cognitively normal individuals and 30 participants with amnestic mild cognitive impairment.


Participants were administered the Cognitive Stress Test and traditional neuropsychological measures. Step-wise logistic regression was applied to determine which Cognitive Stress Test measures best discriminated between diagnostic groups. This was followed by receiver operating characteristic analyses.


Cued A3 recall, Cued B3 recall and Cued B2 intrusions were all independent predictors of diagnostic status. The overall predictive utility of the model yielded 75.9% sensitivity, 91.1% specificity, and an overall correct classification rate of 85.1%. When these variables were jointly entered into receiver operating characteristic analyses, the area under the curve was.923 (p<.001).


This novel paradigm’s use of repeated learning trials offers a unique opportunity to assess recovery from proactive and retroactive semantic interference. Participants with mild cognitive impairment exhibited a continued failure to recover from proactive interference that could not be explained by mere learning deficits.

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Funding: R01AG061106-02 Loewenstein, David, PI; Florida Department of Health Ed and Ethel Moore Grant #8AZ23. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript

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Correspondence to David A. Loewenstein.

Ethics declarations

Conflict of interest: This study was. supported by the National Institute on Aging (NIA). The CST measure was developed by and is intellectual property held by Drs. Loewenstein and Curiel at the University of Miami.

Ethical standards: This study was IRB approved and met all national and international standards for the protection of human subjects.

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Loewenstein, D.A., Curiel Cid, R.E., Kitaigorodsky, M. et al. Amnestic Mild Cognitive Impairment is Characterized by the Inability to Recover from Proactive Semantic Interference across Multiple Learning Trials. J Prev Alzheimers Dis 8, 181–187 (2021).

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Key words

  • Proactive semantic interference
  • retroactive semantic interference
  • prodromal Alzheimer’s disease
  • mild cognitive impairment
  • intrusions