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. 2023 Jan 28;13(2):218.
doi: 10.3390/brainsci13020218.

Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function

Doaa G Ali  1   2 , Erin L Abner  1   3 , Ahmed A Bahrani  1   4 , Riham El Khouli  5 , Brian T Gold  1   6 , Yang Jiang  1   2 , Donna M Wilcock  1   7 , Gregory A Jicha  1   2   4
Affiliations

Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function

Doaa G Ali et al. Brain Sci. .

Abstract

Co-occurrence of beta amyloid (Aβ) and white matter hyperintensities (WMHs) increase the risk of dementia and both are considered biomarkers of preclinical dementia. Moderation and mediation modeling were used to define the interplay between global and regional Aβ and WMHs measures in relation to executive function (EF) and memory composite scores outcomes at baseline and after approximately 2 years across a sample of 714 clinically normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI 2). The moderation regression analysis showed additive effects of Aβ and WMHs over baseline memory and EF scores (p = 0.401 and 0.061, respectively) and synergistic effects over follow-up EF (p < 0.05). Through mediation analysis, the data presented demonstrate that WMHs effects, mediated by global and regional amyloid burden, are responsible for baseline cognitive performance deficits in memory and EF. These findings suggest that Aβ and WMHs contribute to baseline cognition independently while WMHs volumes exert effects on baseline cognitive performance directly and through influences on Aβ accumulation.

Keywords: cognitive function; executive function; neuroimaging; preclinical Alzheimer’s disease; regional standardized uptake value ratio (SUVr); white matter hyperintensities (WMH).

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Conflict of interest statement

The authors do not have any conflict of interest in relation to the submitted manuscript to disclose.

Figures

Figure 1
Figure 1
Longitudinal EF performance at low (−1 SD), moderate mean (0 SD) and high (1 SD) levels of baseline global and regional Aβ burden and WMHs.
Figure 2
Figure 2
Path models of the mediation effect of global and Aβ burden between WMHs and cognitive performance.
Figure 3
Figure 3
Scatterplot between global and regional Aβ burden and WMH volumes.
See this image and copyright information in PMC

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