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Aging Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Recently, interest has emerged in subjective cognitive decline (SCD) as a potential precursor to Alzheimer\u2019s disease (AD) dementia. Whether individuals with SCD harbor brain alterations in midlife, when AD-related pathology begins, is yet to be elucidated. Furthermore, the role of apolipoprotein \u03b54 (<jats:italic>APOE<\/jats:italic> \u03b5<jats:italic>4<\/jats:italic>) allele, a robust AD risk factor, in the relationship between SCD and brain alterations is unknown. We examined whether <jats:italic>APOE<\/jats:italic> genotype modulates the association of SCD with brain measures in individuals at high AD risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Middle-aged adults with parental history of AD dementia underwent magnetic resonance imaging (MRI) and the Memory Functioning Questionnaire. Regression analysis tested the extent to which SCD was associated with activation during an functional MRI (fMRI) working-memory task, and white-matter microstructure. <jats:italic>APOE<\/jats:italic> \u03b5<jats:italic>4<\/jats:italic> genotype was tested as a moderator.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among <jats:italic>APOE<\/jats:italic> \u03b5<jats:italic>4<\/jats:italic> carriers, but not among non-carriers, SCD was associated with higher activation in the anterior cingulate (<jats:italic>p<\/jats:italic> = 0.003), inferior, middle, and superior frontal cortices (<jats:italic>p<\/jats:italic> = 0.041, <jats:italic>p<\/jats:italic> = 0.048, <jats:italic>p<\/jats:italic> = 0.037, respectively); and with lower fractional anisotropy in the uncinate fasciculus (<jats:italic>p<\/jats:italic> = 0.002), adjusting for age, sex, and education.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In middle aged, cognitively normal individuals at high AD risk, higher SCD was associated with greater brain alterations possibly reflecting incipient AD pathology. When accompanied by a family history of AD and an <jats:italic>APOE<\/jats:italic> \u03b5<jats:italic>4<\/jats:italic> allele, SCD may have important clinical value, allowing a window for early intervention and for participants\u2019 stratification in AD prevention clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2023.1067196","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T05:30:33Z","timestamp":1675229433000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Neural correlates of subjective cognitive decline in adults at high risk for Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"15","author":[{"given":"Liat","family":"Ben-Ami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramit","family":"Ravona-Springer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galia","family":"Tsarfaty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reut","family":"Raizman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleeza","family":"Shumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbal","family":"Sharvit-Ginon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Greenbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara B.","family":"Bendlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Okun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Heymann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Schnaider Beeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Livny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e52859","DOI":"10.1371\/journal.pone.0052859","article-title":"Different patterns of white matter degeneration using multiple diffusion indices and volumetric data in mild cognitive impairment and Alzheimer patients.","volume":"7","author":"Alves","year":"2012","journal-title":"PLoS One"},{"key":"B2","year":"2022","journal-title":"Alzheimer\u2019s facts and figures."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1016\/j.neuropsychologia.2012.08.011","article-title":"Subjective cognitive complaints and amyloid burden in cognitively normal older individuals.","volume":"50","author":"Amariglio","year":"2012","journal-title":"Neuropsychologia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1111\/j.1532-5415.2011.03543.x","article-title":"Specific subjective memory complaints in older persons may indicate poor cognitive function.","volume":"59","author":"Amariglio","year":"2011","journal-title":"J. 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