Background <p>Mild cognitive impairment (MCI) is prevalent in patients with coronary heart disease (CHD) and has been linked to alterations in memory-related brain networks. Although computerized cognitive training (CCT) may enhance cognition by promoting neuroplasticity. It remains unknown whether multidomain adaptive CCT can induce structural and functional plasticity within specific memory circuits in patients with CHD and MCI, and whether such neural changes relate to cognitive and cardiovascular outcomes.</p> Methods <p>In this secondary analysis of a multicenter, randomized trial, CHD patients with MCI received either multidomain adaptive CCT or basic CCT as active control. Multimodal MRI, cognitive testing, and blood pressure measurement were conducted at baseline after 12-week intervention. Outcome measures were functional connectivity (FC) of the two memory-related networks included the Parietal Memory Network (PMN) and Context Association Network (CAN), grey matter volume as well as structural connectivity of their key regions, and the association of FC changes with cognitive and blood pressure changes.</p> Results <p>A total of 185 participants (95 in the adaptive CCT group, 90 in the active control group) were eligible. The multidomain training significantly increased hypothesis-driven outcomes, including within-memory network FC (left CAN: <i>p</i> = 0.045; right CAN: <i>p</i> = 0.031; left PMN: <i>p</i> = 0.028) and right PMN whole-brain connectivity (<i>p</i> = 0.010). Exploratory analysis revealed that training-induced FC increased between PMN/CAN and multiple other networks (<i>p</i>_FDR &lt; 0.05). Multidomain CCT also increased grey matter volume in the right precuneus (<i>p</i> = 0.048) and parahippocampal cortex (<i>p</i> = 0.032), and strengthened structural connectivity in the right precuneus–inferior parietal lobule (<i>p</i> = 0.016) and parahippocampal–superior frontal gyrus (<i>p</i> = 0.044) pathways. Improvements in global cognition and working memory were positively associated with changes in FC of PMN (<InlineEquation ID="IEq1"><EquationSource Format="TEX">\(\beta\)</EquationSource></InlineEquation> = 0.23 to 0.36, <i>p</i>s &lt; 0.05) in treatment group. Reductions in systolic blood pressure and pulse pressure were linked to changes in FC of right PMN (<InlineEquation ID="IEq2"><EquationSource Format="TEX">\(\:\beta\:\)</EquationSource></InlineEquation> = -0.25 to 0.31, <i>p</i>s &lt; 0.05), and mediation analyses indicated that FC of right PMN and the cingulo-opercular networks mediated the treatment effect on pulse pressure (<i>p</i> = 0.040).</p> Conclusions <p>Multidomain adaptive CCT promotes functional and structural neuroplasticity in memory-related circuits in CHD patients with MCI. The alterations in functional connectivity were linked to cognitive gains and appeared to mediate the reduction in blood pressure as a modifiable cardiovascular risk factor, indicating that CCT may engage in the brain-heart axis.</p> Trial registration <p>ClinicalTrials.gov, NCT05735041; Registered on Jan. 18, 2023.</p>