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

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.

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