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The Default Mode Network is notably vulnerable to these processes, making early structural alterations in this network of particular interest for identifying prodromal biomarkers. In this longitudinal cross-sectional study, we analysed data from 279 participants in the Alzheimer\u2019s Disease Neuroimaging Initiative (mean age = 73.7 \u00b1 9 years, 53.2% males). Structural measures\u2014sulcal depth, gyrification and cortical thickness\u2014were extracted for all Default Mode Network regions. Their ability to predict memory performance (encoding, retrieval and recall) was tested at baseline and 2-year follow-up by means of multiple linear regression models, which were all corrected for the risk of multiple comparisons. Covariates included Mini Mental State Examination scores, amyloid status and regional tau burden, to examine interactions with structural changes. Our results showed distinct Default Mode Network alteration patterns based on tau burden and amyloid status, highlighting patterns of morphological features with different susceptibility to proteinopathy. In individuals with concordant (both positive or both negative) amyloid and tau status, preserved structural integrity and complexity were linked to better cognitive performance and appeared protective against decline. However, mainly negative associations were instead observed in individuals with discordant amyloid or tau status (i.e. positive for only either amyloid or tau accumulation). We discuss these findings as a possible reflection of a mismatch between abnormal protein accumulation and structural damage in these populations. The multimodal nature of this study helps clarifying the heterogeneous findings reported in existing literature regarding structural integrity and cognitive outcomes in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf320","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T17:59:48Z","timestamp":1756403988000},"source":"Crossref","is-referenced-by-count":2,"title":["Cortical morphology changes in default mode network regions as predictors of cognitive decline in relation to amyloid and tau deposits"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4385-6848","authenticated-orcid":false,"given":"Arianna","family":"Menardi","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Padova , 35128 Padova ,","place":["Italy"]},{"name":"Padova Neuroscience Center, University of Padova , 35131 Padova ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ceren","family":"Saglam","sequence":"additional","affiliation":[{"name":"Department of General Psychology, University of Padova , 35131 Padova ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"La Rocca","sequence":"additional","affiliation":[{"name":"Department of General Psychology, University of Padova , 35131 Padova ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Cecchin","sequence":"additional","affiliation":[{"name":"Padova Neuroscience Center, University of Padova , 35131 Padova ,","place":["Italy"]},{"name":"Department of Medicine (DIMED), University Hospital of Padova , 35128 Padova ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalena","family":"Venneri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma , 43125 Parma ,","place":["Italy"]},{"name":"Department of Neuroscience, University of Sheffield , S10 2TN Sheffield ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annachiara","family":"Cagnin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Padova , 35128 Padova ,","place":["Italy"]},{"name":"Padova Neuroscience Center, University of Padova , 35131 Padova ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4087-2845","authenticated-orcid":false,"given":"Antonino","family":"Vallesi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Padova , 35128 Padova ,","place":["Italy"]},{"name":"Padova Neuroscience Center, University of Padova , 35131 Padova 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