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A total of 563 participants (mean age = 71.9 years, standard deviation = 7.2) from the Alzheimer\u2019s Disease Neuroimaging Initiative were classified by the amyloid-\u03b2\/tau\/neurodegeneration framework into no Alzheimer\u2019s disease pathology (n = 176), suspected non-Alzheimer\u2019s disease pathophysiology (n = 87) or Alzheimer\u2019s disease continuum (n = 300) groups. Participants completed baseline neuropsychological assessment, plasma\/CSF biomarker collection and MRI. Analyses explored the relative contributions of biomarkers to episodic memory and executive function performance and whether relationships varied by amyloid-\u03b2\/tau\/neurodegeneration group status. Across all participants, neurofilament light chain (\u03b2^= \u22120.14, P &amp;lt; 0.001) and growth-associated protein 43 (\u03b2^= \u22120.13, P &amp;lt; 0.001) were the strongest biomarkers associated with episodic memory performance, such that greater levels were associated with worse episodic memory. There was a group by growth-associated protein 43 interaction with episodic memory: greater growth-associated protein 43 was associated with lower episodic memory performance in participants classified as Alzheimer\u2019s disease continuum relative to the no Alzheimer\u2019s disease pathology group (\u03b2^= \u22120.26, P &amp;lt; 0.001). No robust associations between biomarkers and executive function performance or between soluble triggering receptor expressed on myeloid cells 2, white matter hyperintensity volume and cognition were observed. Biomarkers of neuro-axonal injury and synaptic dysfunction may independently contribute to episodic memory performance across participants with differing amyloid-\u03b2\/tau\/neurodegeneration profiles. Growth-associated protein 43 may predict worse episodic memory performance in participants with greater Alzheimer\u2019s disease pathology. These biomarkers of neuronal dysfunction may serve as domain-specific cognitive correlates in the context of Alzheimer\u2019s disease biomarker status.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf068","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T18:03:09Z","timestamp":1739556189000},"source":"Crossref","is-referenced-by-count":1,"title":["Neuronal and glial dysfunction, white matter hyperintensities and cognition in ageing and Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5493-3220","authenticated-orcid":false,"given":"Ann J","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Psychology, The Ohio State University , Columbus, OH 43210 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6688-2059","authenticated-orcid":false,"given":"Erica","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Psychology, The Ohio State University , Columbus, OH 43210 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0033-1814","authenticated-orcid":false,"given":"Nicole","family":"Saltiel","sequence":"additional","affiliation":[{"name":"Department of Psychology, The Ohio State University , Columbus, OH 43210 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5157-0666","authenticated-orcid":false,"given":"Jasmeet P","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Psychology, The Ohio State University , Columbus, OH 43210 ,","place":["USA"]},{"name":"Chronic Brain Injury Initiative, The Ohio State University , Columbus, OH 43210 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1185-5149","authenticated-orcid":false,"given":"Scott M","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Psychology, The Ohio State University , Columbus, OH 43210 ,","place":["USA"]},{"name":"Chronic Brain Injury Initiative, The Ohio State University , Columbus, OH 43210 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"issue":"6","key":"2025022410164605000_fcaf068-B1","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/joim.12816","article-title":"Biomarkers for Alzheimer\u2019s disease: Current status and prospects for the future","volume":"284","author":"Blennow","year":"2018","journal-title":"J Intern 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