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Updated: May 11, 2026
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Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
White Matter Microstructural Alterations Mediate the Association between Polygenic Risk for Alzheimer's Disease and
Rui Zou1,2, Kaito Takabayashi1, Christina Andica1,2,3,4
1Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Summary
Alzheimer's disease polygenic risk scores are linked to white matter changes and cognitive differences in asymptomatic adults. These white matter alterations partially explain the connection between genetic risk and cognitive performance.
Area of Science:
- Neuroimaging
- Genetics
- Cognitive Neuroscience
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a significant genetic component.
- While apolipoprotein E ε4 is a known risk factor, AD is increasingly viewed as polygenic.
- The impact of polygenic risk on white matter (WM) microstructure and cognition in preclinical stages is not well understood.
Purpose of the Study:
- To investigate the associations between Alzheimer's disease polygenic risk scores (ADPRS) and WM microstructure.
- To examine the relationship between ADPRS, WM microstructure, and cognitive performance in clinically asymptomatic adults.
- To determine if WM microstructure mediates the link between ADPRS and cognitive function.
Main Methods:
- Analysis of UK Biobank data from 36,400 individuals (aged 45-83).
- Extraction of diffusion tensor imaging and neurite orientation dispersion and density imaging metrics from 48 WM tracts.
- Application of general linear models and mediation analyses to assess associations and mediation effects.
Main Results:
- Higher ADPRS correlated with reduced fractional anisotropy and intracellular volume fraction in WM tracts.
- Increased diffusivity metrics (mean, axial, radial) and isotropic volume fraction were observed with higher ADPRS.
- ADPRS was associated with poorer performance in executive function, episodic memory, and processing speed, with WM alterations partially mediating these effects.
Conclusions:
- Alzheimer's disease polygenic risk scores are associated with specific white matter microstructural changes in asymptomatic individuals.
- These white matter alterations are linked to subtle cognitive differences.
- White matter microstructural changes partially mediate the relationship between polygenic risk for AD and cognitive performance.
Keywords:
UK Biobankcognitive functionneurite orientation dispersion and density imagingpolygenic risk score of Alzheimer’s diseasewhite matter microstructureMore Related Videos
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