Effects of transcranial direct current stimulation in spoken and written production in primary progressive aphasia

Johns Hopkins University, Baltimore MD

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Abstract

Project Summary Logopenic variant Primary Progressive Aphasia (lvPPA) constitutes a progressive language disorder due to atypical Alzheimer's disease (AD). It is mainly characterized by word finding and repetition deficits. In the parent grant of this supplement we seek to determine the effects of tDCS in PPA including its effects on lvPPA that constitutes approximately one third of PPA cases. In this Administrative Supplement, we extend our focus to the language deficits in typical AD. In general, AD is the most common underlying cause of dementia and one of the most debilitating and costly diseases. Language difficulties are common in patients with AD and in early stages they are manifested as word-retrieval (naming) deficits and in later stages as sentence processing deficits as well. The language deficits in typical AD are usually considered as epiphenomena of primary short- term memory (STM) and working memory (WM) deficits, although this has not been shown to be the case. The main objective of this supplement is to better understand the relationship between STM/WM impairments and language deficits in typical AD and to identify the brain mechanisms involved. In this supplement we will adapt existing tools used for investigating the effects of verbal STM deficits in post-stroke aphasia to address the effects of STM/WM impairments on language in AD. In Specific Aim 1, we will examine the effect of STM/WM impairments on language deficits in people with typical AD compared to age and education matched controls. Patients and controls will undergo a series of language and cognitive evaluations as in the protocol of the parent grant but will additionally also be asked to perform a series of verbal STM tasks with varying degrees of STM load in language as well as visuo-spatial STM tasks. In Specific Aim 2 we will identify the neural substrates involved in the verbal STM (semantic and phonological) and determine whether they predict language performance in AD. We will use MRI structural measures (volumetric, DTI) and dynamic functional connectivity measures (i.e., resting-state fMRI (rsfMRI) focusing on the language, verbal and visuo-spatial STM and the default mode networks). The results from the proposed supplement will inform our understanding of the relationship between STM and language in typical AD both at the behavioral and neural levels. We will be able to better characterize the STM and language deficits in individuals with AD and therefore target rehabilitation efforts on the deficits themselves. Better understanding of the effects of STM/WM on language and vice versa will help optimize and extend the non-invasive treatments investigated tDCS in the parent grant to the language deficits of individuals with typical AD.