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We investigated whether plasma p-tau217, p-tau181, and neurofilament light chain (NfL) are associated with domain-specific longitudinal cognitive changes in SCD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>76 SCD patients underwent plasma biomarker assessment and extensive neuropsychological evaluation at baseline and after two years. Participants were classified according to plasma biomarker status: p-tau217-negative, gray-zone, or positive; p-tau181-negative or positive; and NfL-negative or positive. Linear mixed effects models with random intercepts were used to assess the effects of time, biomarker status, and their interaction on cognitive outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma p-tau217 showed the most consistent association with longitudinal cognitive trajectories. p-Tau217-positive participants declined in short story delayed recall and visual search, while gray-zone participants showed an intermediate memory trajectory. For category fluency, p-tau217-negative participants improved over time. Plasma p-tau181 showed weaker and less consistent associations, mainly involving memory measures and emerging primarily in post hoc analysis. NfL was associated with a more heterogeneous profile, without a clear pattern of longitudinal cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Plasma p-tau217 was associated with early domain-specific cognitive vulnerability in SCD, involving episodic memory and attentional functioning. These findings suggest that plasma p-tau217 showed more consistent associations with early domain-specific cognitive changes than p-tau181 and NfL, supporting its role in cognitive stratification of individuals within the earliest stages of the AD continuum.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13966-z","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T03:54:25Z","timestamp":1782446065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma p-tau217 best captures early longitudinal cognitive changes in subjective cognitive decline compared with p-tau181 and NfL"],"prefix":"10.1007","volume":"273","author":[{"given":"Giulia","family":"Giacomucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Pieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bagnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia Maria","family":"Giametta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Padiglioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Moschini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Morinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Maria Rita","family":"Tabb\u00ec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sensi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Mistretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Crucitti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9338-9040","authenticated-orcid":false,"given":"Benedetta","family":"Nacmias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Bessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"issue":"8","key":"13966_CR1","doi-asserted-by":"publisher","first-page":"5143","DOI":"10.1002\/alz.13859","volume":"20","author":"CR Jack","year":"2024","unstructured":"Jack CR, Andrews JS, Beach TG et al (2024) Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup. 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