{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wuestefeld A"],"funding":["Vetenskapsrådet","NIA NIH HHS","Stiftelsen För Gamla Tjänarinnor","Department of Defense","MultiPark - A Strategic Research Area at Lund University","Bente Rexed Gerstedt Foundation","NIH HHS"],"pagination":["e70511"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12290488"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(7)"],"pubmed_abstract":["<h4>Introduction</h4>A granular understanding of the mechanisms linking tau pathology to cognitive decline in Alzheimer's disease is crucial. We investigate mediating effects of medial temporal lobe (MTL) and neocortical neurodegeneration on tau-induced domain-specific cognitive impairment in amyloid-beta (Aβ) positive cognitively normal and impaired adults.<h4>Methods</h4>We assessed magnetic resonance imaging-derived MTL and neocortical volume/thickness and <sup>18</sup>F-Flortaucipir positron emission tomography in 319 Aβ-positive individuals. Cognitive functions across six domains were isolated by adjusting for other cognitive measures.<h4>Results</h4>MTL tau correlated with memory subdomains, neocortical tau with executive function, and both with semantic fluency. Specific structural measures partially mediated these tau-cognition associations: Brodmann area 35 mediated tau-immediate and tau-delayed recall, posterior hippocampus tau-recognition, and inferior temporal cortex tau-semantic fluency associations.<h4>Discussion</h4>Our findings provide a nuanced understanding of region-specific macrostructural atrophy as one pathway of tau-induced cognitive changes, aligning with known tau spread patterns. Additionally, isolating cognitive functions is a promising approach for future research.<h4>Highlights</h4>Medial temporal lobe tau was related to memory domains; neocortical tau to executive function. Both tau positron emission tomography measures were associated with semantic fluency. Specific regional atrophy partially mediated tau-induced cognitive changes. Other mechanistic links between tau and cognitive subdomains require investigation. Isolated cognitive domains should be explored as future avenues of research."],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["Tau, atrophy, and domain-specific cognitive impairment in typical Alzheimer's disease."],"pmcid":["PMC12290488"],"funding_grant_id":["RF1-AG056014","P30-AG072979","U01 AG024904","2024-250","W81XWH-12-2-0012","U19-AG024904","2022-00900","R01-AG070592","R01-AG069474"],"pubmed_authors":["Wisse LEM","and for the Alzheimer's Disease Neuroimaging Initiative","van Westen D","Xie L","McGrew E","Pichet-Binette A","Mattsson-Carlgren N","Das SR","Spotorno N","Wolk DA","Yushkevich PA","Wuestefeld A"],"additional_accession":[]},"is_claimable":false,"name":"Tau, atrophy, and domain-specific cognitive impairment in typical Alzheimer's disease.","description":"<h4>Introduction</h4>A granular understanding of the mechanisms linking tau pathology to cognitive decline in Alzheimer's disease is crucial. We investigate mediating effects of medial temporal lobe (MTL) and neocortical neurodegeneration on tau-induced domain-specific cognitive impairment in amyloid-beta (Aβ) positive cognitively normal and impaired adults.<h4>Methods</h4>We assessed magnetic resonance imaging-derived MTL and neocortical volume/thickness and <sup>18</sup>F-Flortaucipir positron emission tomography in 319 Aβ-positive individuals. Cognitive functions across six domains were isolated by adjusting for other cognitive measures.<h4>Results</h4>MTL tau correlated with memory subdomains, neocortical tau with executive function, and both with semantic fluency. Specific structural measures partially mediated these tau-cognition associations: Brodmann area 35 mediated tau-immediate and tau-delayed recall, posterior hippocampus tau-recognition, and inferior temporal cortex tau-semantic fluency associations.<h4>Discussion</h4>Our findings provide a nuanced understanding of region-specific macrostructural atrophy as one pathway of tau-induced cognitive changes, aligning with known tau spread patterns. Additionally, isolating cognitive functions is a promising approach for future research.<h4>Highlights</h4>Medial temporal lobe tau was related to memory domains; neocortical tau to executive function. Both tau positron emission tomography measures were associated with semantic fluency. Specific regional atrophy partially mediated tau-induced cognitive changes. Other mechanistic links between tau and cognitive subdomains require investigation. Isolated cognitive domains should be explored as future avenues of research.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-03-15T17:10:47.122Z","creation":"2025-08-13T03:04:36.579Z"},"accession":"S-EPMC12290488","cross_references":{"pubmed":["40709494"],"doi":["10.1002/alz.70511"]}}