Tehran University of Medical Sciences Frontiers in Biomedical Technologies 2345-5837 0 0 2026 06 16 1079 1079 EN Leila Golchin Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Maryam Noroozian Professor of neurology, Director; Cognitive Neurology, Dementia and Neuropsychiatry (CNNRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran Seyed Amir Hossein Batouli Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran. Mohammad Ali Oghabian Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran. Research Center for Molecular and Cellular Imaging (RCMCI), Tehran, Iran, http://Rcmci.tums.ac.ir 2024 08 04 2025 01 08 Purpose: Primary Progressive Aphasia (PPA) is a neurodegenerative syndrome characterized by progressive language impairment. The present study investigated white matter (WM) microstructural changes in PPA patients and their relationship with language and neuropsychological functions. Materials and Methods: Diffusion tensor imaging (DTI) was used to examine 29 PPA patients and 13 healthy controls, focusing on 18 white matter tracts in both hemispheres. Results: Significant differences in diffusivity values were observed between PPA patients and controls in multiple tracts, including the Cingulum, Arcuate Fasciculus (AF), Superior Longitudinal Fasciculus (SLF), Inferior Fronto-Occipital Fasciculus (IFOF), Inferior Longitudinal Fasciculus (ILF) bilaterally, as well as the left Uncinate Fasciculus (UF). Correlations between WM integrity and language functions were found in both hemispheres, with the left Cingulum showing positive correlations with various language measures. Notably, right hemisphere tracts (IFOF, ILF, SLF) positively correlated with several language domains, suggesting a potential compensatory role. White matter microstructural changes also correlated with neuropsychological functions, highlighting PPA's interconnections of language and cognitive domains. Conclusion: To our knowledge, the present study is the first to identify specific correlations between right hemisphere tracts, language domains, and cognitive functions in PPA patients. Our findings contribute to understanding the neural basis of language impairment in PPA, emphasizing the bilateral nature of language processing in neurodegenerative disorders. The results have implications for diagnosis, prognosis, and treatment planning in PPA, suggesting the need for therapeutic approaches that consider both hemispheres and the interplay between language and broader cognitive functions. https://fbt.tums.ac.ir/index.php/fbt/article/view/1079 https://fbt.tums.ac.ir/index.php/fbt/article/download/1079/569