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. 2023;94(2):695-707.
doi: 10.3233/JAD-221209.

White Matter Hyperintensity Volume and Amyloid-PET Synergistically Impact Memory Independent of Tau-PET in Older Adults Without Dementia

Lauren Edwards  1 , Kelsey R Thomas  2   3 , Alexandra J Weigand  1 , Emily C Edmonds  4   5 , Alexandra L Clark  6 , Kayla S Walker  7 , Einat K Brenner  3 , Daniel A Nation  8 , Pauline Maillard  9 , Mark W Bondi  3   10 , Katherine J Bangen  2   3 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

White Matter Hyperintensity Volume and Amyloid-PET Synergistically Impact Memory Independent of Tau-PET in Older Adults Without Dementia

Lauren Edwards et al. J Alzheimers Dis. 2023.

Abstract

Background: Alzheimer's disease (AD) and cerebrovascular disease are common, co-existing pathologies in older adults. Whether the effects of cerebrovascular disease and AD biomarkers on cognition are additive or synergistic remains unclear.

Objective: To examine whether white matter hyperintensity (WMH) volume moderates the independent association between each AD biomarker and cognition.

Methods: In 586 older adults without dementia, linear regressions tested the interaction between amyloid-β (Aβ) positron emission tomography (PET) and WMH volume on cognition, independent of tau-PET. We also tested the interaction between tau-PET and WMH volume on cognition, independent of Aβ-PET.

Results: Adjusting for tau-PET, the quadratic effect of WMH interacted with Aβ-PET to impact memory. There was no interaction between either the linear or quadratic effect of WMH and Aβ-PET on executive function. There was no interaction between WMH volume and tau-PET on either cognitive measure.

Conclusion: Results suggest that cerebrovascular lesions act synergistically with Aβ to affect memory, independent of tau, highlighting the importance of incorporating vascular pathology into biomarker assessment of AD.

Keywords: Alzheimer’s disease; amyloid-β; executive function; memory; tau; white matter hyperintensities.

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Conflict of interest statement

Dr. Bondi is a paid consultant for Eisai, Novartis and Roche Pharmaceuticals and receives royalties from Oxford University Press.

Dr. Thomas, Dr. Nation, Dr. Bondi, and Dr. Bangen are Editorial Board members of the Journal of Alzheimer’s Disease and were not involved in peer reviewing the present paper.

No other authors have competing interests to declare.

Figures

Fig. 1
Fig. 1
The effects of Aβ centiloids on cognition at varying levels of white matter hyperintensity burden. A) Aβ burden does not interact with either the linear or quadratic effect of white matter hyperintensity volume to effect executive function. B) Aβ burden interacts with the quadratic effect of white matter hyperintensity volume to effect memory, independent of tau-PET.
Fig. 2
Fig. 2
The effects of tau-PET on cognition at varying levels of white matter hyperintensity burden. There is no amyloid-independent interaction between tau-PET and either the linear or quadratic effects of white matter hyperintensity volume on either (A) executive function or (B) memory.
See this image and copyright information in PMC

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