Tabriz Valiasr International Hospital Publication International Journal of Aging 2980-9827 3 1 2025 01 12 Association of Aging and Structure Connectome With Cognitive Performance: A Systematic Review e9125 e9125 10.34172/ija.9125 EN Mahdi Zahmatyar https://orcid.org/0000-0001-9719-6844 Pedram Heidari‎ Alireza Motamedi ‎ Fatemeh Abbasi Salva Ilkhani Sama Rahnemayan Mahsa Karbasi Atena Akbari Sahar Rezaei https://orcid.org/0000-0002-2746-6594 Esmaeil Gharepapagh https://orcid.org/0000-0002-3864-6304 Journal Article 10.34172/ija.9125 2025 08 01 2025 10 01 Objectives: To systematically review evidence on the association between aging-related alterations in the structural connectome, particularly white matter microstructure, and cognitive performance. Design: Systematic review. Participants: Older adults without clinically diagnosed neurological disorders from 24 eligible studies. Outcome Measures: Diffusion tensor imaging (DTI)-derived indices of white matter microstructure, including fractional anisotropy and mean diffusivity, and cognitive outcomes encompassing working memory, attention, processing speed, and executive function. Results: The majority of included studies demonstrated that advancing age was associated with reduced white matter integrity. These alterations were consistently linked to poorer performance across multiple cognitive domains, particularly processing speed, executive function, and working memory. Multimodal studies integrating DTI with functional MRI further suggested that aging weakens structural–functional coupling and reduces network efficiency, which may contribute to less effective cognitive and spatial processing. However, substantial heterogeneity in sample characteristics, imaging protocols, and analytic approaches limited direct comparison across studies. Conclusions: The current evidence supports a robust association between age-related white matter microstructural changes and cognitive decline. These alterations may represent early markers of cognitive vulnerability and could help identify individuals at increased risk for future cognitive impairment or dementia. Larger longitudinal studies with standardized acquisition and analytic methods are needed to clarify the predictive value of these markers and strengthen causal inference.