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Record W4412654096 · doi:10.1002/alz.70511

Tau, atrophy, and domain‐specific cognitive impairment in typical Alzheimer's disease

2025· article· en· W4412654096 on OpenAlexaff
Anika Wuestefeld, Long Xie, Emily McGrew, Alexa Pichet Binette, Nicola Spotorno, Danielle van Westen, Niklas Mattsson, Paul A. Yushkevich, Sandhitsu R. Das, David A. Wolk, Laura E.M. Wisse

Bibliographic record

VenueAlzheimer s & Dementia · 2025
Typearticle
Languageen
FieldMedicine
TopicDementia and Cognitive Impairment Research
Canadian institutionsUniversité de MontréalInstitut Universitaire de Gériatrie de Montréal
FundersVetenskapsrådetNational Institutes of HealthNational Institute on AgingLunds UniversitetStiftelsen för Gamla TjänarinnorU.S. Department of Defense
KeywordsAtrophyCognitive impairmentDiseaseCognitionPsychologyNeuroscienceMedicinePathology

Abstract

fetched live from OpenAlex

INTRODUCTION: 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. METHODS: F-Flortaucipir positron emission tomography in 319 Aβ-positive individuals. Cognitive functions across six domains were isolated by adjusting for other cognitive measures. RESULTS: 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. DISCUSSION: 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. HIGHLIGHTS: 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.309
Teacher spread0.290 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations8
Published2025
Admission routes1
Has abstractyes

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