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Dementia"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) biomarkers are assessed on their ability to detect AD pathophysiology in vivo, with confirmation of AD neuropathology only at autopsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Positron emission tomography (PET), plasma, and cognitive AD biomarkers were compared to AD neuropathology in Harvard Aging Brain Study participants (10 cognitively unimpaired; 6 mild cognitive impairment). Different PET methods were evaluated, for example, standardized uptake volume ratio (SUVR), distribution volume ratio (DVR), spatial extent (EXT), and partial\u2010volume correction (PVC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Amyloid beta (A\u03b2)\u2013PET (\n                      <jats:sup>11<\/jats:sup>\n                      C\u2010Pittsburgh compound B [PiB]), tau\u2010PET (\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010flortaucipir [FTP]), and plasma tau phosphorylated at threonine 217 (p\u2010tau217) correlate with A\u03b2 plaques (A\u2010score), Braak tau neurofibrillary tangle (NFT) stage (B\u2010score), and neuritic plaques (C\u2010score), whereas plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and cognitive measures did not; although digital Clock Drawing Test (dCDT) latency features did, in an exploratory comparison. Correlations were stronger for A\u03b2\u2010PET DVR and A\u03b2\u2010PET EXT (than SUVR with\/without PVC) and tau\u2010PET SUVR (composite reference and PVC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings support the innovative use of imaging, plasma, and digital cognitive tools for detecting AD pathophysiology in a largely cognitively unimpaired population.<\/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>Amyloid beta\u2013positron emission tomography (A\u03b2\u2010PET), tau\u2010PET imaging, and plasma tau phosphorylated at threonine 217 (p\u2010tau217) correlate with ABC scores<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Correlations were larger for A\u03b2\u2010PET distribution volume ratio (DVR) and tau\u2010PET standardized uptake volume ratio (SUVR; composite reference, partial volume correction [PVC])<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Digital Clock Drawing Test latency features correlate with A\u2010 and Cscores<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Standard cognitive measures mostly did not correlate with ABC scores<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) biomarkers did not correlate with ABC scores<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71092","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:00:30Z","timestamp":1767891630000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identifying early changes in imaging, plasma, and digital cognitive biomarkers that correspond to Alzheimer's disease pathology in the presence of autopsy\u2010confirmed co\u2010pathologies"],"prefix":"10.1002","volume":"22","author":[{"given":"Charles D.","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology Harvard Medical School Massachusetts General Hospital  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinthya","family":"Aguero","sequence":"additional","affiliation":[{"name":"Department of Neurology Harvard Medical 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