P2-462: semantic richness in people with preclinical alzheimer's disease

Patients with preclinical Alzheimer's disease display evidence of cerebral amyloid, but perform normally on neuropsychological assessment. Measures sensitive to subtle cognitive change early in the disease would have significant impact for screening and measuring outcomes in intervention studies. We tested the hypothesis that semantic richness changes early in the AD trajectory, using tests adapted from the psycholinguistic and language-learning literatures, and relate performance to structural imaging in MTL regions and to amyloid status. We tested cognitively normal (CN) older adults (n = 39) and MCI patients (n = 34) on tests of semantic processing predicted to be sensitive to early cognitive dysfunction including (1) a receptive measure of depth of vocabulary, the Word Associates Test (WAT) in which participants choose four correctly matching synonyms or collocates from eight possibilities for each item; (2) A senses-listing task, in which participants are given one minute to list as many senses as possible for target words chosen from normed databases; and (3) a non-semantic, visual-spatial analogy task requiring participants to identify patterns in sets of colored geometric shapes. MTL segmentation was performed in T1-weighted MRI using an analysis pipeline prescribed for subregional MTL measures, including anterior/posterior hippocampus, entorhinal cortex (ERC), BA35 (i.e. tansentorhinal cortex), BA36, and parahippocampus. Amyloid PET was dichotomized as positive or negative. Linear mixed-effects models related test scores to MTL measures and amyloid status. Performance across semantic tasks differentiated MCI patients from CN participants (ps < 0.05). Integrity of MTL subregions vulnerable to earliest AD pathology, including BA35, predicted performance on the semantic tasks (Figures 1 and 2, ps < 0.01) in the CN group. Amyloid positive CN adults (i.e. preclinical AD; n=12) displayed a trend of poorer performance on semantic tasks relative to amyloid negative CN adults (n=27, p < 0.1). The visual-spatial analogy task didn't differentiate groups, relate to MTL atrophy, or amyloid status, reflecting the specificity of the semantic tasks.