Background: Accumulating evidence indicates that the failure to recover from the effects of
proactive semantic interference [frPSI] represents an early cognitive manifestation of preclinical Alzheimer's
disease. A limitation of this novel paradigm has been a singular focus on the number of targets
correctly recalled, without examining co-occurring semantic intrusions [SI] that may highlight specific
breakdowns in memory.
Objectives: We focused on SI and their relationship to amyloid load and regional cortical thickness
among persons with amnestic mild cognitive impairment (aMCI).
Methods: Thirty-three elders diagnosed with aMCI underwent F-18 florbetaben amyloid PET scanning
with MRI scans of the brain. We measured the correlation of SI elicited on cued recall trials of the
Loewenstein-Acevedo Scales for Semantic Interference and Learning [LASSI-L] with mean cortical
amyloid load and regional cortical thickness in AD prone regions.
Results: SI on measures sensitive to frPSI was related to greater total amyloid load and lower overall
cortical thickness [CTh]. In particular, SI were highly associated with reduced CTh in the left entorhinal
cortex [r=-.71; p<.001] and left medial orbital frontal lobe [r=-.64; p<.001]; together accounting for 66%
of the explained variability in regression models.
Conclusion. Semantic intrusions on measures susceptible to frPSI related to greater brain amyloid load
and lower cortical thickness. These findings further support the hypothesis that frPSI, as expressed by
the percentage of intrusions, may be a cognitive marker of initial neurodegeneration and may serve as an
early and distinguishing test for preclinical AD that may be used in primary care or clinical trial settings.