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We analyzed blood DNAm samples from &gt; 1000 cognitively unimpaired subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Meta\u2010analysis identified 44 CpGs and 44 differentially methylated regions consistently associated with time to dementia in both cohorts. Our integrative analysis identified early processes in dementia, such as immune responses and metabolic dysfunction. Furthermore, we developed a methylation\u2010based risk score, which successfully predicted future cognitive decline in an independent validation set, even after accounting for age, sex, apolipoprotein E \u03b54, years of education, baseline diagnosis, and baseline Mini\u2010Mental State Examination score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>DNAm offers a promising source as a biomarker for dementia risk assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Blood DNA methylation (DNAm) differences at individual CpGs and differentially methylated regions are significantly associated with incident dementia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pathway analysis revealed DNAm differences associated with incident dementia are significantly enriched in biological pathways involved in immune responses and metabolic processes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Out\u2010of\u2010sample validation analysis demonstrated that a methylation\u2010based risk score successfully predicted future cognitive decline in an independent dataset, even after accounting for age, sex, apolipoprotein E \u03b54, years of education, baseline diagnosis, and baseline Mini\u2010Mental State Examination score.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14496","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T02:10:45Z","timestamp":1743127845000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Blood DNA methylation signature for incident dementia: Evidence from longitudinal cohorts"],"prefix":"10.1002","volume":"21","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Biostatistics Department of Public Health Sciences Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan I.","family":"Young","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics Miller School of Medicine University of Miami  Miami Florida USA"},{"name":"John P. Hussman Institute for Human Genomics Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lissette","family":"Gomez","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics Miller School of Medicine University of Miami  Miami Florida USA"},{"name":"John P. 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Steven","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Biostatistics Department of Public Health Sciences Miller School of Medicine University of Miami  Miami Florida USA"},{"name":"Sylvester Comprehensive Cancer Center Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eden R.","family":"Martin","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics Miller School of Medicine University of Miami  Miami Florida USA"},{"name":"John P. Hussman Institute for Human Genomics Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics Department of Public Health Sciences Miller School of Medicine University of Miami  Miami Florida USA"},{"name":"Dr. John T. 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