{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:28:10Z","timestamp":1786976890429,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Assessing brain health and identifying cognitive impairment risk remains challenging, with only 11.4% of MCI cases receiving timely diagnoses. We developed the Brain Health Index (BHI), integrating the Vulnerability Index, Resilience Index, and Number Symbol Coding Task into a unified metric.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We evaluated 469 participants (258 congnitively normal [CN], 140 mild cognitive impairment [MCI], 49 Alzheimer's disease and related dementias [ADRD]) using comprehensive clinical, cognitive, and biomarker assessments. After empirically\u2010derived weighting, BHI thresholds were developed. Cross\u2010sectional associations and longitudinal analyses were performed, with threshold validation for risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      BHI demonstrated strong correlations with cognitive (Montreal Cognitive Assessment [MoCA]\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.408), functional (Functional Activities Questionnaire [FAQ]\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.278), and biomarker (neurofilament light chain [NfL]\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.073) measures. Complete mediation was observed for NfL and glial fibrillary acidic protein (GFAP) changes over 1 year. Threshold analysis revealed 89.2% of low BHI participants had cognitive impairment, with only one ADRD case in the high BHI group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The BHI provides a brief, validated, comprehensive brain health metric with clinical utility for risk stratification and intervention monitoring.<\/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>Assessing brain health status and identifying individuals at risk for cognitive impairment remains a significant challenge, particularly in early prodromal and symptomatic stages when current therapies may be most effective and patients may be eligible for clinical trials.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We created a unified metric, the Brain Health Index (BHI), combining resilience and vulnerability factors with cognitive performance that divided individuals into high, indeterminant, and low risk groups.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The BHI demonstrated strong correlations with cognitive, functional, and biomarker measures.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The BHI had a 16\u2010fold increase in identifying individuals who were likely to have cognitive impairment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The BHI provides a brief, validated, comprehensive brain health metric with clinical utility for risk stratification and intervention monitoring.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70723","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:18:11Z","timestamp":1758705491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Brain Health Index: Integrating vulnerability, resilience, and cognitive function into a unified measure of cognitive health and risk of neurodegenerative disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Michael J.","family":"Kleiman","sequence":"first","affiliation":[{"name":"Comprehensive Center for Brain Health Department of Neurology University of Miami Miller School of Medicine  Boca Raton Florida 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