Tau, atrophy, and domain-specific cognitive impairment in typical Alzheimer's disease
Wuestefeld, Anika LU
; Xie, Long
; McGrew, Emily
; Pichet-Binette, Alexa
LU
; Spotorno, Nicola
LU
; van Westen, Danielle
LU
; Mattsson-Carlgren, Niklas
LU
; Yushkevich, Paul A
; Das, Sandhitsu R
and Wolk, David A
, et al.
(2025)
In Alzheimer's & dementia : the journal of the Alzheimer's Association
21(7).
- Abstract
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: We assessed magnetic resonance imaging-derived MTL and neocortical volume/thickness and 18F-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... (More)
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: We assessed magnetic resonance imaging-derived MTL and neocortical volume/thickness and 18F-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.
(Less)
- author
- Wuestefeld, Anika
LU
; Xie, Long
; McGrew, Emily
; Pichet-Binette, Alexa
LU
; Spotorno, Nicola
LU
; van Westen, Danielle
LU
; Mattsson-Carlgren, Niklas
LU
; Yushkevich, Paul A
; Das, Sandhitsu R
and Wolk, David A
, et al. (More)
- Wuestefeld, Anika
LU
; Xie, Long
; McGrew, Emily
; Pichet-Binette, Alexa
LU
; Spotorno, Nicola
LU
; van Westen, Danielle
LU
; Mattsson-Carlgren, Niklas
LU
; Yushkevich, Paul A
; Das, Sandhitsu R
; Wolk, David A
and Wisse, Laura E M
LU
(Less)
- author collaboration
- organization
-
- LU Profile Area: Proactive Ageing
- Clinical Memory Research (research group)
- MultiPark: Multidisciplinary research focused on Parkinson's disease
- eSSENCE: The e-Science Collaboration
- Neuroradiology (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- Brain Injury After Cardiac Arrest (research group)
- Diagnostic Radiology, (Lund)
- publishing date
- 2025-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Humans, Alzheimer Disease/pathology, Male, Female, tau Proteins/metabolism, Atrophy/pathology, Positron-Emission Tomography, Cognitive Dysfunction/pathology, Magnetic Resonance Imaging, Aged, Temporal Lobe/pathology, Neuropsychological Tests, Middle Aged, Amyloid beta-Peptides/metabolism, Neocortex/pathology
- in
- Alzheimer's & dementia : the journal of the Alzheimer's Association
- volume
- 21
- issue
- 7
- article number
- e70511
- publisher
- Wiley
- external identifiers
-
- pmid:40709494
- ISSN
- 1552-5279
- DOI
- 10.1002/alz.70511
- language
- English
- LU publication?
- yes
- additional info
- © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
- id
- aa7c60f2-2934-4554-9cb8-f0e01c82e27a
- date added to LUP
- 2025-08-04 07:37:15
- date last changed
- 2025-08-04 12:29:30
@article{aa7c60f2-2934-4554-9cb8-f0e01c82e27a,
abstract = {{<p>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.</p><p>METHODS: We assessed magnetic resonance imaging-derived MTL and neocortical volume/thickness and 18F-Flortaucipir positron emission tomography in 319 Aβ-positive individuals. Cognitive functions across six domains were isolated by adjusting for other cognitive measures. </p><p>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.</p><p>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.</p><p>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.</p>}},
author = {{Wuestefeld, Anika and Xie, Long and McGrew, Emily and Pichet-Binette, Alexa and Spotorno, Nicola and van Westen, Danielle and Mattsson-Carlgren, Niklas and Yushkevich, Paul A and Das, Sandhitsu R and Wolk, David A and Wisse, Laura E M}},
issn = {{1552-5279}},
keywords = {{Humans; Alzheimer Disease/pathology; Male; Female; tau Proteins/metabolism; Atrophy/pathology; Positron-Emission Tomography; Cognitive Dysfunction/pathology; Magnetic Resonance Imaging; Aged; Temporal Lobe/pathology; Neuropsychological Tests; Middle Aged; Amyloid beta-Peptides/metabolism; Neocortex/pathology}},
language = {{eng}},
number = {{7}},
publisher = {{Wiley}},
series = {{Alzheimer's & dementia : the journal of the Alzheimer's Association}},
title = {{Tau, atrophy, and domain-specific cognitive impairment in typical Alzheimer's disease}},
url = {{http://dx.doi.org/10.1002/alz.70511}},
doi = {{10.1002/alz.70511}},
volume = {{21}},
year = {{2025}},
}