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Recent neuroimaging and pharmacological studies reported that left frontoparietal network functional connectivity (LFPN-FC) confers resilience against beta-amyloid (A\u03b2)-related cognitive decline in preclinical sporadic and autosomal dominant Alzheimer\u2019s disease (AD), as well as against LC-related cognitive changes. Given that the LFPN and the LC play important roles in attention, and attention deficits have been observed early in the disease process, we examined whether LFPN-FC and LC structural health attenuate attentional decline in the context of AD pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>142 participants from the Harvard Aging Brain Study who underwent resting-state functional MRI, LC structural imaging, PiB(A\u03b2)-PET, and up to 5 years of cognitive follow-ups were included (mean age\u2009=\u200974.5\u2009\u00b1\u20099.9 years, 89 women). Cross-sectional robust linear regression associated LC integrity (measured as the average of five continuous voxels with the highest intensities in the structural LC images) or LFPN-FC with Digit Symbol Substitution Test (DSST) performance at baseline. Longitudinal robust mixed effect analyses examined associations between DSST decline and (i) two-way interactions of baseline LC integrity (or LFPN-FC) and PiB or (ii) the three-way interaction of baseline LC integrity, LFPN-FC, and PiB. Baseline age, sex, and years of education were included as covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, lower LFPN-FC, but not LC integrity, was related to worse DSST performance. Longitudinally, lower baseline LC integrity was associated with a faster DSST decline, especially at PiB\u2009&gt;\u200910.38 CL. Lower baseline LFPN-FC was associated with a steeper decline on the DSST but independent of PiB. At elevated PiB levels (&gt;\u200946 CL), higher baseline LFPN-FC was associated with an attenuated decline on the DSST, despite the presence of lower LC integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate that the LC can provide resilience against A\u03b2-related attention decline. However, when A\u03b2 accumulates and the LC\u2019s resources may be depleted, the functioning of cortical target regions of the LC, such as the LFPN-FC, can provide additional resilience to sustain attentional performance in preclinical AD. These results provide critical insights into the neural correlates contributing to individual variability at risk versus resilience against A\u03b2-related cognitive decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13195-024-01485-w","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T03:04:59Z","timestamp":1717124699000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Locus coeruleus integrity and left frontoparietal connectivity provide resilience against attentional decline in preclinical alzheimer\u2019s disease"],"prefix":"10.1186","volume":"16","author":[{"given":"Jennifer","family":"Pahl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prokopis C.","family":"Prokopiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisenda","family":"Bueichek\u00fa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron P.","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn V.","family":"Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Farrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorene M.","family":"Rentz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa A.","family":"Sperling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi I.L.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"issue":"11","key":"1485_CR1","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1097\/NEN.0b013e318232a379","volume":"70","author":"H Braak","year":"2011","unstructured":"Braak H, Thal DR, Ghebremedhin E, Del Tredici K. 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All participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A.P.S. has been a paid consultant for Janssen Pharmaceuticals and Biogen. K.V.P. is funded by NIA grant K23 AG053422-01 and the Alzheimer\u2019s Association and has served as a paid consultant for Biogen. R.A.S. has served as paid consultant for AC Immune, Alector, Acumen, Bristol Myers Squibb, Genentech, NervGen, Oligomerix, Prothena, Renew, Vigil Neuroscience, Ionis, and Vaxxinity. She receives research support from Eisai and Eli Lilly as part of public-private partnership clinical trials, and also receives research support from the following grants: P01 AG036694, U24\u202fAG057437, R01\u202fAG063689,\u202fR01\u202fAG054029,\u202fR01\u202fAG053798, GHR Foundation,\u202fNational Institute on Aging,\u202fFidelity Biosciences, and the Alzheimer\u2019s Association. K.A.J. has served as paid consultant for Janssen, Genzyme, Novartis, Biogen, Roche, and AC Immune. He is a site co- investigator for Lilly\/Avid and Janssen, and receives research support for clinical trials from Eisai, Lilly and Cerveau. He received funding from NIH grants R01 EB014894, R21 AG038994, R01 AG026484, R01 AG034556, P50 AG00513421, U19 AG10483, P01 AG036694, R13 AG042201174210, R01 AG027435, and R01 AG037497 and the Alzheimer\u2019s Association grant ZEN-10-174210. These relationships are not related to the content of the manuscript. All other authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"119"}}