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

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 compensatory mechanisms.Fil: Curiel, Rosie E.. University of Miami; Estados UnidosFil: Crocco, Elizabeth A.. University of Miami; Estados UnidosFil: Raffo, Arlene. University of Miami; Estados UnidosFil: Guinjoan, Salvador Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Nemeroff, Charles B.. University of Miami; Estados UnidosFil: Penate, Ailyn. Mount Sinai Medical Center; Estados Unidos. University of Miami; Estados UnidosFil: Piña, Daema. University of Miami; Estados UnidosFil: Loewenstein, David A.. Mount Sinai Medical Center; Estados Unidos. University of Miami; Estados Unido

A cognitive stress test for prodromal Alzheimer's disease: Multiethnic generalizability

Culturally fair cognitive assessments sensitive to detecting changes associated with prodromal Alzheimer's disease are needed. Performance of Hispanic and non-Hispanic older adults on the Loewenstein-Acevedo Scale of Semantic Interference and Learning (LASSI-L) was examined in persons with amnestic mild cognitive impairment (aMCI) or normal cognition. The association between a novel cognitive marker, the failure to recover from proactive semantic interference (frPSI), and cortical thinning was explored. English-speaking aMCI participants scored lower than cognitively normal participants on all LASSI-L indices, while Spanish-speaking aMCI participants scored lower in learning, frPSI, and delayed recall. Healthy controls obtained equivalent scores on all indices except retroactive semantic interference. English-speaking and Spanish-speaking aMCI participants had equivalent scores except English speaker's greater vulnerability to frPSI. Across aMCI groups, frPSI was associated with cortical thinning of the entorhinal cortex and precuneus (r = −0.45 to r = 0.52; P < .005). In diverse populations, LASSI-L performance differentiated patients with aMCI from cognitively normal older adults and was associated with thinning in Alzheimer's disease–prone regions, suggesting its clinical utility. •Culturally fair outcome measures sensitive to detecting prodromal Alzheimer's disease are needed.•The Loewenstein-Acevedo Scale of Semantic Interference and Learning differentiates amnestic mild cognitive impairment from cognitively normal Hispanic elderly, a growing minority group.•A sensitive marker, failure to recover from proactive semantic interference, was implicated in amnestic mild cognitive impairment, regardless of culture/language.•The failure to recover from proactive semantic interference was associated with cortical thinning in Alzheimer's disease–prone regions