Divergent white matter metabolic signature patterns indicate impending cognitive decline in aging and dementia.

Wen Zhang, Sheelakumari Raghavan, Jianqiao Tian, Scott A Przybelski, Heather J Wiste, Angela J Fought, Matthew L Senjem, Christopher G Schwarz, Robert I Reid, Mary M Machulda, Ronald C Petersen, Jonathan Graff-Radford, Clifford R Jack, Val J Lowe, Prashanthi Vemuri

Department of Radiology, Mayo Clinic, Rochester, MN, USA.Department of Radiology, Mayo Clinic, Rochester, MN, USA. · pubmed

Paper

Abstract

White matter (WM) is a key substrate for interregional neural communication and cognitive function but the role of WM glucose metabolism in cognitive aging has been understudied. Using multimodal neuroimaging (MRI, FDG-PET, amyloid-PET) from 3142 participants (15,287 visits) across two studies, we examined the contribution of WM to cognition and identified divergent WM signatures. Higher glucose metabolism in expected WM (EWM; corpus callosum and cingulum) was associated with better cognition, whereas increased metabolism in atypical WM (AWM; corona radiata) was linked to worse cognition, indicating a compensatory mechanism. EWM metabolism declined with aging, Alzheimer's disease (AD) progression (amyloid-β and APOE-ε4 carrier), and white matter hyperintensities, while AWM metabolism increased with aging and vascular risk but was partially weakened by AD neuropathology. Longitudinally, higher EWM and lower AWM metabolism predicted slower cognitive decline. Divergent WM metabolic patterns shed light on the dynamic role of WM in maintaining cognitive function. This study emphasizes the complementary information provided by WM metabolism for predicting future cognitive decline and identifying cognitive resilience.

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Research summary

Higher glucose metabolism in expected white matter is associated with better cognition, while increased metabolism in atypical white matter is linked to worse cognition. The study explores the role of white matter metabolism in cognitive aging, which is relevant to understanding mechanisms underlying cognitive decline and resilience in aging populations.

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