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This study employed a positron emission tomography \u2010validated, non\u2010invasive magnetic resonance imaging (MRI) technique to characterize longitudinal changes in cerebral metabolic rate of oxygen (CMRO\n                      <jats:sub>2<\/jats:sub>\n                      ) in both cognitively normal and impaired older adults.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Participants received serial MRI\u2010based CMRO\n                      <jats:sub>2<\/jats:sub>\n                      scans between 2015 and 2025. Levels of AD pathology were measured in cerebrospinal fluid and plasma at the initial MRI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      At the initial visit, participants with MCI\/dementia had lower CMRO\n                      <jats:sub>2<\/jats:sub>\n                      than normal participants. In the longitudinal analyses, CMRO\n                      <jats:sub>2<\/jats:sub>\n                      decreased over time in those who were cognitively impaired but remained unchanged in normals. Among normal participants, higher initial levels of total tau and phosphorylated tau at threonine 181 were associated with an increase in CMRO\n                      <jats:sub>2<\/jats:sub>\n                      during follow\u2010up, especially in amyloid\u2010positive individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Aside from the well\u2010known metabolic slowdown in the later phases of AD, the brain exhibits tau\u2010dependent hypermetabolism during the preclinical stage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71561","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:21:38Z","timestamp":1781065298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Five\u2010year change in brain metabolism across the spectrum of cognitive impairment in older adults: a quantitative MRI study"],"prefix":"10.1002","volume":"22","author":[{"given":"Jiani","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Radiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Soldan","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Pettigrew","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengrong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Gou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Radiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay","family":"Moghekar","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Diagnostic Radiology &amp; 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