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DL-3-n-butylphthalide (NBP) has been confirmed to exert neuroprotective effects through multiple pathways and thereby enhance cognitive function. However, the role of NBP in the ChP volume remains unclear at present.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This trial aimed to explore the clinical efficacy of NBP in patients with mild cognitive impairment (MCI) and its corresponding ChP imaging characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This randomized, double-masked, placebo-controlled study included 270 MCI patients, randomly assigned in a 1:1 ratio to receive either NBP or placebo. Concurrently, all participants received clinical cognitive evaluations and 3D T1-weighted magnetic resonance imaging scans at both baseline and post-treatment phases. The objective was to evaluate the efficacy of 12-month NBP treatment on cognitive impairment and investigate the neuroimaging correlates of NBP therapy, focusing specifically on longitudinal alterations in ChP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The NBP treatment significantly improved the cognitive symptoms of MCI patients, which was strongly correlated with the decrease in ChP volume in the drug group. Moreover, subgroup analysis indicated that cognitive enhancement was closely related to changes in ChP volume in the effective group. Mediation effect analysis revealed that ChP volume partially mediated the enhancement of cognitive symptoms in MCI patients undergoing NBP treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This research provided evidence that NBP may improve cognitive symptoms in MCI patients by regulating changes in ChP volume, as well as offered insight into identifying early neuroimaging markers of MCI and drug targets for NBP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registry name<\/jats:title>\n                    <jats:p>Efficacy and safety of butylphthalide on patients with mild cognitive impairment; Registration number: ChiCTR1800018362<\/jats:p>\n                  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