Relatively spared during most of the timeline of normal aging, semantic memory shows a subtle yet measurable decline even during the pre-clinical stage of Alzheimer's disease. This decline is thought to reflect early neurofibrillary changes and impairment is detectable using tests of language relying on lexical-semantic abilities. A promising approach is the characterization of semantic parameters such as typicality and age of acquisition of words, and propositional density from verbal output. Seminal research like the Nun Study or the analysis of the linguistic decline of famous writers and politicians later diagnosed with Alzheimer's disease supports the early diagnostic value of semantic processing and semantic memory. Moreover, measures of these skills may play an important role for the prognosis of patients with mild cognitive impairment.

Objective: Given that lexical-semantic decline precedes episodic memory deficits in the Alzheimer disease (AD) timeline, it is expected that performance on a lexical-semantic task would be associated with mediotemporal volumes independently of the association this region has with episodic memory in the early stage of AD. Methods: Fifty patients with MCI due to AD and fifty healthy adults completed tests of lexical-semantic skills (Category Fluency), episodic memory for semantically-relevant material (Prose Memory), episodic memory for non-semantically-relevant material (Rey-Osterrieth Figure) and lexical-executive abilities (Letter Fluency), and a neurostructural MRI. Hippocampal, perirhinal, entorhinal, temporopolar and orbitofrontal volumes were extracted. The association between test performance and volume of each region was tested using partial correlations (age-education corrected). The improvement (r-squared change) at predicting volumetric indices offered by episodic memory/lexical-semantic processing, once accounting for their counterpart was tested using hierarchical regressions. Results: There were no significant findings for control indices. Prose Memory accounted for independent portions of volumetric variability within almost all regions. Category Fluency accounted for independent portions of volumetric variability of left/right hippocampus and left perirhinal cortex additional to the predictive strength of the Rey-Osterrieth Figure, and for an independent portion of volumetric variability in the left hippocampus additional to the predictive strength of Prose Memory. Conclusions: There was an association between hippocampal and perirhinal volume and lexicalsemantic processing, additional to the contribution given by episodic memory. This statistical separation supports the importance of lexical-semantic processing as independent indicator of AD.