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

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-beta (A beta) positron emission tomography (PET) andWMHvolume on cognition, independent of tau-PET. We also tested the interaction between tau-PET and WMH volume on cognition, independent of A beta-PET. Results: Adjusting for tau-PET, the quadratic effect of WMH interacted with A beta-PET to impact memory. There was no interaction between either the linear or quadratic effect ofWMHand A beta-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 A beta to affect memory, independent of tau, highlighting the importance of incorporating vascular pathology into biomarker assessment of AD.

Automated summary

This study found that white matter hyperintensity (WMH) volume can moderate the association between AD biomarkers and cognition, with a quadratic effect between WMH and A beta on memory; however, there was no interaction between linear or quadratic effects of WMH and A beta on executive function; additionally, there was no interaction between WMH volume and tau-PET on cognitive measures.