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Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010114","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer's disease and coronary artery disease are common late-life chronic conditions and share multiple risk factors, including the apolipoprotein E (APOE) \u03b54 allele. A meta-analysis of two multidomain lifestyle intervention trials found greater cognitive benefits in APOE4 carriers compared with non-carriers. This study investigated the impact of genetic risk scores for Alzheimer's disease and coronary artery disease (AD-GRS, CAD-GRS) on cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) randomized controlled trial.<\/jats:p>\n                  <jats:p>FINGER included 1259 at-risk individuals without dementia from the general population, aged 60\u201377 years. Participants were randomized 1:1 to a 2-year multidomain lifestyle intervention or regular health advice. The primary outcome was change in cognition based on a modified Neuropsychological Test Battery (14 tests). Previous comprehensive AD-GRS and CAD-GRS were calculated using genome-wide association study data (1177 participants, with 585 in the control and 592 in the intervention groups, exploratory analysis).<\/jats:p>\n                  <jats:p>The intervention-control difference in annual overall cognition change (95% confidence interval) for participants with AD-GRS above\/below the median (i.e. higher\/lower risk) was 0.032 (0.002\u20130.063) versus 0.017 (\u22120.011 to 0.045), and for CAD-GRS above\/below the median was 0.031 (0.002 to 0.059) versus 0.016 (\u22120.012 to 0.044). AD-GRS or CAD-GRS were not significantly related to the intervention effect overall (P &amp;gt; 0.46), but for AD-GRS there were differences between females and males (P = 0.024). The intervention-control difference in annual overall score change was 0.045 (0.004 to 0.087) for higher-risk females, 0.003 (\u22120.040 to 0.047) for lower-risk females, 0.019 (\u22120.026 to 0.064) for higher-risk males, and 0.027 (\u22120.009 to 0.064) for lower-risk males.<\/jats:p>\n                  <jats:p>People with genetic susceptibility for Alzheimer's disease\/dementia or coronary artery disease can benefit from multidomain lifestyle interventions. Although the findings for the AD-GRS and CAD-GRS risk groups were similar to APOE4 carrier status, with additional gender differences for AD-GRS, these exploratory findings need to be verified across several multidomain lifestyle trials to ensure adequate statistical power and inclusion of genetically diverse populations.<\/jats:p>","DOI":"10.1093\/brain\/awaf277","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T11:39:57Z","timestamp":1753961997000},"page":"644-652","source":"Crossref","is-referenced-by-count":2,"title":["Alzheimer and cardiovascular genetic scores and cognition: the FINGER randomized controlled trial"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0925-7609","authenticated-orcid":false,"given":"Gazi","family":"Saadmaan","sequence":"first","affiliation":[{"name":"Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carolina","family":"Dalmasso","sequence":"additional","affiliation":[{"name":"Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce, National University A. 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Virtanen Institute for Molecular Sciences, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8818-0848","authenticated-orcid":false,"given":"Jenni","family":"Lehtisalo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]},{"name":"Department of Public Health, Finnish Institute for Health and Welfare , Helsinki 00300 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Hiltunen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6294-0979","authenticated-orcid":false,"given":"Minna U","family":"Kaikkonen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esko","family":"Lev\u00e4lahti","sequence":"additional","affiliation":[{"name":"Department of Public Health, Finnish Institute for Health and Welfare , Helsinki 00300 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mangialasche","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , Stockholm 171 76 ,","place":["Sweden"]},{"name":"Medical Unit Aging, Theme Inflammation and Aging, Karolinska University Hospital , Stockholm 171 76 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4842-1667","authenticated-orcid":false,"given":"Markus","family":"Perola","sequence":"additional","affiliation":[{"name":"Department of Public Health, Finnish Institute for Health and Welfare , Helsinki 00300 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-763X","authenticated-orcid":false,"given":"Alfredo","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty , Cologne 50923 ,","place":["Germany"]},{"name":"Department of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, University of Bonn , Bonn 53127 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE Bonn) , Bonn 53127 ,","place":["Germany"]},{"name":"Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center , San Antonio, TX 78229 ,","place":["USA"]},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Disease (CECAD), University of Cologne , Cologne 50923 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Stephen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]},{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , Stockholm 171 76 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3698-2021","authenticated-orcid":false,"given":"Tiia","family":"Ngandu","sequence":"additional","affiliation":[{"name":"Department of Public Health, Finnish Institute for Health and Welfare , Helsinki 00300 ,","place":["Finland"]},{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , Stockholm 171 76 ,","place":["Sweden"]},{"name":"Institute of Public Health and Clinical Nutrition, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miia","family":"Kivipelto","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , Stockholm 171 76 ,","place":["Sweden"]},{"name":"Medical Unit Aging, Theme Inflammation and Aging, Karolinska University Hospital , Stockholm 171 76 ,","place":["Sweden"]},{"name":"Institute of Public Health and Clinical Nutrition, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]},{"name":"Ageing Epidemiology Research Unit, School of Public Health, Imperial College London , London W6 8RP ,","place":["UK"]},{"name":"Research and Development Unit, Stockholm Sjukhem , Stockholm 112 19 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]},{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , Stockholm 171 76 ,","place":["Sweden"]},{"name":"Ageing Epidemiology Research Unit, School of Public Health, Imperial College London , London W6 8RP ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"2026020710020712200_awaf277-B1","volume-title":"Risk reduction of cognitive decline and dementia: WHO guidelines","author":"World Health Organization","year":"2019"},{"key":"2026020710020712200_awaf277-B2","first-page":"CD001561","article-title":"Multiple risk factor interventions for primary prevention of coronary heart disease","volume":"2011","author":"Ebrahim","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"2026020710020712200_awaf277-B3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.jalz.2012.09.012","article-title":"The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): Study design and 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