{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:02:31Z","timestamp":1777395751927,"version":"3.51.4"},"reference-count":60,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2022,8,30]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease is characterized by the accumulation of amyloid-\u03b2 (A\u03b2) into plaques, aggregation of tau into neurofibrillary tangles, and neurodegenerative processes including atrophy. However, there is a poorly understood spatial discordance between initial A\u03b2 deposition and local neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Here, we test the hypothesis that the cingulum bundle links A\u03b2 deposition in the cingulate cortex to medial temporal lobe (MTL) atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>21 participants with mild cognitive impairment (MCI) from the UMC Utrecht memory clinic (UMCU, discovery sample) and 37 participants with MCI from Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI, replication sample) with available A\u03b2-PET scan, T1-weighted and diffusion-weighted MRI were included. A\u03b2 load of the cingulate cortex was measured by the standardized uptake value ratio (SUVR), white matter integrity of the cingulum bundle was assessed by mean diffusivity and atrophy of the MTL by normalized MTL volume. Relationships were tested with linear mixed models, to accommodate multiple measures for each participant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We found at most a weak association between cingulate A\u03b2 and MTL volume (added R\n                      <jats:sup>2<\/jats:sup>\n                      &lt;0.06), primarily for the posterior hippocampus. In neither sample, white matter integrity of the cingulum bundle was associated with cingulate A\u03b2 or MTL volume (added R\n                      <jats:sup>2<\/jats:sup>\n                      &lt;0.01). Various sensitivity analyses (A\u03b2-positive individuals only, posterior cingulate SUVR, MTL sub region volume) provided similar results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings, consistent in two independent cohorts, do not support our hypothesis that loss of white matter integrity of the cingulum is a connecting factor between cingulate gyrus A\u03b2 deposition and MTL atrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-220024","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T11:46:03Z","timestamp":1657626363000},"page":"39-49","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Does Loss of Integrity of the Cingulum Bundle Link Amyloid-\u03b2 Accumulation and Neurodegeneration in Alzheimer\u2019s Disease?"],"prefix":"10.1177","volume":"89","author":[{"given":"Naomi","family":"Vlegels","sequence":"first","affiliation":[{"name":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"Ossenkoppele","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Clinical Memory Research Unit, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Department of Epidemiology and Data Science, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiberdina L.","family":"Koek","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yael D.","family":"Reijmer","sequence":"additional","affiliation":[{"name":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura EM","family":"Wisse","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geert Jan","family":"Biessels","sequence":"additional","affiliation":[{"name":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 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