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The fact that a wide range of neuropathologies could only explain up to 43% of the variation in age-related cognitive impairment suggests that other factors, such as cognitive reserve, may play a role in the brain\u2019s resilience against aging-related cognitive decline. This study aims to examine the relationship between structural\u2013functional-connectivity coupling (SFC), and aging, cognitive abilities and reserve, and SVD-related neuropathologies using a cohort of <jats:italic>n<\/jats:italic>\u2009=\u2009176 healthy elders from the Harvard Aging Brain Study. The SFC is a recently proposed biomarker that reflects the extent to which anatomical brain connections can predict coordinated neural activity. After controlling for the effect of age, sex, and years of education, global SFC, as well as the intra-network SFC of the dorsolateral somatomotor and dorsal attention networks, and the inter-network SFC between dorsolateral somatomotor and frontoparietal networks decreased with age. The global SFC decreased with total cognitive score. There were significant interaction effects between years of education versus white matter hyperintensities and between years of education versus cerebral microbleeds on inter-network SFC. Enlarged perivascular space in basal ganglia was associated with higher inter-network SFC. Our results suggest that cognitive ability is associated with brain coupling at the global level and cognitive reserve with brain coupling at the inter-functional-brain-cluster level with interaction effect from white matter hyperintensities and cerebral microbleed in a cohort of healthy elderlies.<\/jats:p>","DOI":"10.1007\/s11357-024-01106-2","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T01:02:06Z","timestamp":1709686926000},"page":"3875-3887","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The structural\u2013functional-connectivity coupling of the aging brain"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8313-0756","authenticated-orcid":false,"given":"Hui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry K. 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