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Adair Charitable Foundation"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    Loss of locus coeruleus (LC) integrity, a debilitating feature of Alzheimer\u2019s disease (AD), can be visualized in vivo with MRI. Longitudinal investigation across the AD spectrum can elucidate the timing of LC damage and its behavioral correlates. Cognitively normal adults (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u2009153), individuals with mild cognitive impairment (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200973), and with AD (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200943) underwent MR imaging to assess LC integrity, PET imaging to assess tau and A\u03b2 ([\n                    <jats:sup>18<\/jats:sup>\n                    F]MK6240 and [\n                    <jats:sup>18<\/jats:sup>\n                    F]AZD4694, respectively) and completed a battery of cognitive tests. For a subset of participants, these assessments were repeated annually for up to 4\u2009years. Linear mixed effects analysis examined the association of time and cognitive performance with LC signal. Reduction in LC integrity over time was significant for patients early in the course of AD (\n                    <jats:italic toggle=\"yes\">t<\/jats:italic>\n                    <jats:sub>95<\/jats:sub>\n                    \u2009=\u2009\u22123.72,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.0003) but not in later AD phases or healthy aging. In AD participants, several cognitive measures correlated with LC integrity including logical memory (\n                    <jats:italic toggle=\"yes\">t<\/jats:italic>\n                    <jats:sub>64<\/jats:sub>\n                    \u2009=\u20092.57,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.013) and object recognition (\n                    <jats:italic toggle=\"yes\">t<\/jats:italic>\n                    <jats:sub>64<\/jats:sub>\n                    \u2009=\u20093.41,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.001). LC imaging reveals degeneration of the LC-norepinephrine system within subjects over time in early AD phases. LC damage correlates to cognitive impairment and the strong relationship observed of LC signal to object recognition could suggest an important role of this system in novelty detection in AD.\n                  <\/jats:p>","DOI":"10.1177\/0271678x261460160","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T04:16:07Z","timestamp":1780719367000},"page":"2623-2633","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["A longitudinal investigation of locus coeruleus norepinephrine system integrity and cognitive performance across the Alzheimer\u2019s spectrum"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2132-6176","authenticated-orcid":false,"given":"Ahmad","family":"Sibahi","sequence":"first","affiliation":[{"name":"Institute of Mental Health Research, University of Ottawa, Ottawa, ON, 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