Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-07-08 DOI:10.1002/alz.70435

Ellen Hanna Singleton, Niklas Mattsson-Carlgren, Alexa Pichet Binette, Erik Stomrud, Olof Strandberg, Sebastian Palmqvist, Rik Ossenkoppele, Oskar Hansson

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Abstract

INTRODUCTION

The independent contributions of baseline and longitudinal tau positron emission tomography (PET) and magnetic resonance imaging (MRI) to cognitive decline remain unclear.

METHODS

We included n = 761 amyloid-positive individuals from the Swedish BioFINDER-2 study with [¹⁸F]RO948-tau-PET, 3-Tesla structural-MRI, and cognition (n = 322 with longitudinal imaging data). Linear-mixed-models with random-intercepts and -slopes or linear-regressions were adjusted for age, sex, education, diagnosis, and other-imaging-modality.

RESULTS

Tau-PET showed stronger associations with cognitive decline than MRI, showing the strongest associations in a neocortical-composite-region with a cognitive composite (β = −0.25 ± 0.02, p < 0.001) for baseline and longitudinal tau-PET (β = −0.62 ± 0.05, p < 0.001). Baseline tau-PET explained the largest proportion of cognitive decline (54.0%–94.0%), with modest mediation effects for longitudinal tau-PET or MRI pathways (2.0%–15.0%). Simulated reductions of tau-PET-slopes (up to 100%) were associated with marginally altered cognitive trajectories.

DISCUSSION

The strong associations between baseline tau-PET and longitudinal cognition, with marginal contributions of longitudinal tau-PET and MRI, emphasize the importance of baseline tau aggregates for prognostics and treatments in Alzheimer's disease (AD).

Highlights

Baseline and longitudinal regional tau-PET uptake were more closely associated than structural MRI with longitudinal cognitive decline.
Baseline tau-PET was a stronger determinant of longitudinal cognitive decline than longitudinal tau-PET.
Simulated reductions of tau-PET accumulation showed limited alterations of cognitive trajectories, with potential implications for tau-targeting therapies.

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阿尔茨海默病的纵向tau聚集、萎缩和认知能力下降

基线和纵向tau正电子发射断层扫描（PET）和磁共振成像（MRI）对认知能力下降的独立贡献尚不清楚。方法我们纳入了来自瑞典BioFINDER-2研究的n = 761例淀粉样蛋白阳性个体，使用[18F]RO948-tau-PET、3-Tesla结构mri和认知（n = 322例纵向成像数据）。根据年龄、性别、教育程度、诊断和其他影像模式调整具有随机截距和斜率或线性回归的线性混合模型。结果与MRI相比，Tau-PET显示认知能力下降的相关性更强，其中新皮质复合区与认知复合区相关性最强(β = - 0.25±0.02,p <；0.001)，基线和纵向tau-PET (β = - 0.62±0.05,p <；0.001)。基线tau-PET解释了认知能力下降的最大比例（54.0%-94.0%），纵向tau-PET或MRI通路有适度的中介作用（2.0%-15.0%）。模拟tau- pet斜率的降低（高达100%）与认知轨迹的轻微改变有关。基线tau- pet和纵向认知之间的强烈关联，以及纵向tau- pet和MRI的边际贡献，强调了基线tau聚集对阿尔茨海默病（AD）预后和治疗的重要性。基线和纵向区域性tau-PET摄取与纵向认知能力下降的关系比结构MRI更密切。基线tau-PET比纵向tau-PET更能决定纵向认知能力下降。模拟tau-PET积累的减少显示认知轨迹的有限改变，这对tau靶向治疗具有潜在的意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.