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However, substantial interindividual variability in response persists, and identifying individuals more likely to benefit from the intervention remains challenging. Blood\u2010based biomarkers (BBMs), which provide a minimally invasive means of assessing Alzheimer's disease (AD)\u2010related pathological processes, may help identify biologically distinct subgroups of individuals with mild cognitive impairment (MCI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Blood\u2010based biomarkers\u2014including amyloid\u2010\u03b242\/40 ratio, phosphorylated tau\u2010217, neurofilament light chain, and glial fibrillary acidic protein (GFAP)\u2014were measured in J\u2010MINT participants. Hierarchical clustering based on BBM profiles was used to identify biologically defined subgroups. Whole\u2010genome sequencing data were analyzed using genome\u2010wide association analysis (GWAS) to identify genetic variants associated with the BBM\u2010based subgroup. A prediction model for the subgroup assignment was constructed using the associated incorporating the genetic variants, age, sex, and apolipoprotein E4 (\n                      <jats:italic>APOE4)<\/jats:italic>\n                      allele count. Model performance was evaluated using five\u2010fold cross\u2010validation repeated 1000 times.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      BBM\u2010based clustering identified a subgroup characterized by elevated GFAP and multiple biomarker abnormalities. Within this subgroup, the change in cognitive performance from baseline to 18 months differed significantly between intervention and control groups, with greater decline observed in the control group. GWAS identified four variants showing suggestive association with the subgroup, two of which were located in intronic regions of genes associated with hearing loss (\n                      <jats:italic>PCDH15<\/jats:italic>\n                      and\n                      <jats:italic>ATP11A<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>BBM\u2010based clustering identified biologically distinct subgroups among individuals with MCI. The subgroup characterized by multiple biomarker abnormalities and elevated GFAP showed differential cognitive trajectories between the intervention and control groups. These findings suggest that BBMs, potentially in combination with genetic information, may help identify individuals with a more progressive AD\u2010related biological profile who may derive greater benefit from multidomain intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70329","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:01:03Z","timestamp":1792148463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integration of blood\u2010based biomarkers and genomic variants identifies individuals with mild cognitive impairment who benefit from multidomain intervention"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2010-104X","authenticated-orcid":false,"given":"Tetsuaki","family":"Kimura","sequence":"first","affiliation":[{"name":"Medical Genome Center Research Institute, National Center for Geriatrics and 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