{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:07:53Z","timestamp":1789560473132,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171198"],"award-info":[{"award-number":["82171198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Various indicators of neurodegeneration (N) are used in the assessment of neuronal injury in Alzheimer's disease (AD). The heterogeneity of such indicators is less clear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A total of 416 individuals with different cognitive statuses were recruited for this study. Differential associations of hippocampal volume (HV), 18F\u2010fluorodeoxyglucose positron emission tomography (FDG PET) standardized uptake value ratios (SUVRs), and plasma neurofilament light chain (NfL) levels with amyloid beta (A\u03b2)\u2013tau pathology and cognitive impairment were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>HV decreased early during the high A\u03b2 burden but tau\u2010negative stage. FDG PET SUVRs and plasma NfL levels notably changed at tau\u2010positive stages. HV and plasma NfL correlated with cognitive scores in the early to middle stages, while FDG PET SUVRs aligned with cognitive decline from the middle to late stages. Hippocampal atrophy and inferior parietal hypometabolism increased the risk of cognitive impairment in A+T+, while adding NfL+ had no additional impact within the distinct A\/T groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Different indicators of N have varying relationships to AD pathology and cognitive impairment.<\/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>Hippocampal atrophy emerges early with a\u00a0high amyloid beta burden and exacerbates during the tau\u2010positive phase.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Brain hypometabolism and elevated plasma neurofilament light chain (NfL) levels appear mainly in tau\u2010positive stages.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hippocampal volume and plasma NfL levels correlate with cognitive decline in the early to middle stages, while 18F\u2010fluorodeoxyglucose positron emission tomography standardized uptake value ratios in the\u00a0middle to late stages.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hippocampal atrophy and inferior parietal hypometabolism raise the risk of cognitive impairment in amyloid\/tau\u2013positive individuals while adding NfL+ shows no additional effect.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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