An Emerging Model of Word Retrieval in Preclinical Alzheimer ’s Disease

Abstract

IntroductionWord retrieval deficit in persons on the Alzheimer's disease (AD) spectrum [1] has been investigated mostly in AD dementia and, to a smaller degree, in patients with mild cognitive impairment (MCI). In contrast, word retrieval abilities in persons at the presumably earliest stage of AD, i.e. in preclinical AD have not been systematically investigated so far. Even though these persons do not present with cognitive symptoms characteristic of MCI and AD, they do exhibit subtle cognitive changes and changes in brain activation patterns [2]. Therefore, the preclinical stage of AD is a unique window into the earliest dynamics of cognitive deterioration emerging under the burden of Alzheimer's pathology.One particularly intriguing question regarding initial cognitive deterioration in AD is how the ability to retrieve words from memory relates to structural and functional changes that have already taken place in the brain at this presumably earliest point in the AD trajectory. Among the brain changes that have been associated with preclinical AD are increased cortical levels of the amyloid-β (Aβ) protein and decreasedCSF amyloid levels together with high levels of tau proteins, considerable temporo-parietal hypometabolism spreading to the frontal lobe, less pronounced grey matter volume reductions and cortical thinning, changes in white matter integrity, and aberrant resting-state functional connectivity patterns [2][3][4][5][6]. This phase of illness may take more than 10 years [7] and "losing words" may begin at any point during this time. When and how this happens is currently not clear.One part of the problem pertains to the fact that word retrieval is a complex process that requires fine-tuning of memory, attention, and language processes. Current theories of the human word-store postulate that the mental lexicon contains information on words' meanings (semantics), their role in a sentence (syntax), and what they sound like (phonology). The mental lexicon of a normal adult literate person contains 50-100 thousand words. The average rate of word production is 2-3 words per second, with only one or two errors occurring in 1000 words [8]. Most researchers agree that retrieving a word from the mental lexicon requires a preliminary conceptual step, followed by a lexical selection (which means access to semantic and syntactic features of the target word), and retrieval of its phonological code, with further steps involving the specifics leading to the word's articulation [9,10]. AbstractWord retrieval deficit in persons on the Alzheimer's disease (AD) spectrum has been investigated mostly in AD dementia and, to a smaller degree, in patients with mild cognitive impairment. However, recent evidence suggests that changes in word retrieval abilities are also present in persons at the presumably earliest stage of AD, i.e. in preclinical AD. Considering this evidence as well as previous findings on word retrieval difficulties in cognitively healthy elderly persons, the present paper outlines a novel model of word ...