P1‐479: RELATIONSHIPS BETWEEN ALZHEIMER'S DISEASE BIOMARKERS ON SEMANTIC CUEING AND TOTAL RECALL IN THE FREE AND CUED SELECTIVE REMINDING TEST (FSCRT)

Abstract

Semantic cueing (SC) can enhance performance on learning and recall tasks. SC may be a sensitive measure for detecting early neurocognitive changes in individuals with preclinical Alzheimer's disease (pAD). While free delayed recall is dependent on both the Papez circuit and distributed cortical networks, SC is especially sensitive to deficits in the Papez circuit that is affected early in AD. The present study examined SC in a series of cognitively normal subjects that had undergone structural MRI and CSF analyses for Aβ and tau in order to test the hypothesis that SC deficits can predict pAD. Inclusion/exclusion criteria included Mini-Mental Status Exam (MMSE) score of ≥26 (indicating intact global cognition), a Hachinski Ischemic Scale (HIS) score <4 (indicating low cerebrovascular risk), and no significant medical or neurologic disease that could cause cognitive deficits. The Free and Cued Selective Reminding Test (FCSRT), 3D-MPRAGE T1 sequences on MRI, and CSF were collected on 66 cognitively normal participants seen at the University of Kentucky Alzheimer's Disease Center. Linear regression was used to examine relationships between SC recall, cortical thickness, and CSF. Participants had a mean MMSE score of 28.7 ± 1.8, age of 73.9 ± 5.7 years, an education of 16.6 ± 2.5 years, and were 52.9% female. None of these variables were significant predictors of pAD. While higher CSF Aβ levels were significantly associated with free recall (β=0.025, p=0.01), they showed no association with SC. In contrast, increased levels of CSF tau were significantly associated with decreased SC recall performance (β=0.001, p=0.002). The association of decreased CSF Aβ with free delayed recall but not SC suggests dysfunction in cortical and other brain regions, with relative sparing of the Papez circuit. In contrast, the present data demonstrates that SC is associated with both the presence of tau abnormalities in CSF and entorhinal cortex atrophy, which is indicative of active neurofibrillary tangle pathology. While SC recall does not appear to predict amyloid positivity, it appears to be associated with neuropsychological change early in the neurofibrillary tangle cascade. These results allow for the development of more effective neuropsychological assessments for individuals with preclinical Alzheimer's disease.