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Nocturnal hypoxemia, which can be more severe during rapid eye movement (REM) sleep, may be a key mechanism. This study examines how REM hypoxemia affects memory and explores whether hippocampal vulnerability to hypoxemia mediates this effect in older adults at risk for dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Older adults aged \u226550\u2009years (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009338) with subjective or mild cognitive impairment (i.e., objective impairment) underwent neuropsychological, mood, and medical assessment, magnetic resonance imaging scanning (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009135), and overnight polysomnography. Verbal learning and memory were assessed with the Rey Auditory Verbal Learning Test. REM sleep hypoxemia was measured using the Oxygen Desaturation Index\u20103% (REM\u2010ODI). Hippocampal subfield (CA1, CA3, subiculum, and dentate gyrus) volumes were derived from T1 and high\u2010resolution hippocampus T2 scans. We determined whether the relationship between REM\u2010ODI and learning and memory was mediated by hippocampal subfield volume. Analyses were repeated in non\u2010REM sleep to determine whether the effects were REM\u2010specific.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Although there was not a direct effect of REM\u2010ODI on verbal learning (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05) or memory (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05), mediation analyses showed a significant indirect effect of high REM\u2010ODI on poorer verbal learning (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.09, 95% confidence interval [CI] = \u22120.238 to \u22120.005) and memory (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.100, 95% CI = \u22120.255 to \u22120.005), which was mediated by CA1 volume. These associations were absent in non\u2010REM sleep (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Hypoxemia during REM sleep may impair memory in people at risk for dementia by reducing CA1 hippocampal volume. Research is needed to explore whether interventions targeting REM sleep hypoxemia are protective against memory decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.16491","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T09:26:54Z","timestamp":1727170014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hypoxemia during rapid eye movement sleep mediates memory impairment in older adults at risk for dementia via\n                    <scp>CA1<\/scp>\n                    hippocampal volume loss"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6087-3565","authenticated-orcid":false,"given":"Aaron","family":"Lam","sequence":"first","affiliation":[{"name":"Healthy Brain Ageing Program, Brain and Mind Centre University of Sydney  Sydney New South Wales Australia"},{"name":"Faculty of Science, School of Psychology University of 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