LANGUAGE NETWORK ALTERATIONS IN ALZHEIMER’S DISEASE AND A SEMANTIC VARIANT OF PRIMARY PROGRESSIVE APHASIA PATIENTS

Abstract

Both patients with semantic variant primary progressive aphasia (svPPA) and Alzheimer's disease (AD) can present with similar language impairments. It has been hypothesized that these deficits are associated with different brain mechanisms in each disease, but no previous study has used a network approach to explore this hypothesis. The aim of this study is to investigate and directly compare the resting-state functional magnetic resonance imaging (rs-fMRI) language network in AD, svPPA patients and cognitively unimpaired elderly adults (CTRL). In this study, 9 svPPA patients, 10 AD patients and 11 CTRL, matched on age, gender, and education, were recruited. rs-fMRI preprocessing and seed-based analyses were conducted using the CONN toolbox in SPM12. Seed regions (8-mm spheres) were placed in the left posterior middle temporal gyrus (pMTG), left inferior frontal gyrus (IFG) and left anterior temporal lobe (ATL), consistently with recent descriptions of the language rs-fMRI network. Functional networks were obtained for each group and contrasts were established to map the voxels that expressed a stronger functional association between groups (p≤.05 cluster-level FDR corrected). In svPPA patients, decreased functional connectivity was observed in the left ATL in comparison to CTRL and AD patients, while the pMTG, the IFG and the other language regions remained functionally interconnected. In AD patients, significant decreased functional connectivity was observed between the left pMTG and right-hemisphere language regions, in comparison to CTRL. Interestingly, while CTRL presented significant connectivity between language regions and key regions of the default-mode network (DMN), AD patients did not, although this result did not reach statistical significance in the direct comparison between groups. Overall, the complete isolation of the left ATL in svPPA is consistent with the semantic breakdown observed in these patients and support the role of this region as the epicenter of this disease. In AD, decreased long-range functional connectivity between the left pMTG and the right hemisphere language regions might be related to semantic access impairments. The fact that the DMN is the main targeted network in AD and that it presents overlap with the language network might also contribute to language symptoms.