Linking white matter hyperintensities to regional cortical thinning, amyloid deposition, and synaptic density loss in Alzheimer's disease

Abstract

Introduction: We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH-connected cortex using multimodal images.

Methods: We included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aβ) positivity on amyloid positron emission tomography (PET). The cortex connected to WMH was identified using probabilistic tractography.

Results: We found that WMH connected to the cortex with more severe regional degeneration as measured by cortical thickness, Aβ and tau deposition, and synaptic vesicle glycoprotein 2 A (SV2A) density using ¹⁸F-SynVesT-1 PET. In addition, higher ratios of Aβ in the deep WMH-connected versus WMH-unconnected cortex were significantly related to lower cognitive scores. Last, the cortical thickness of WMH-connected cortex reduced more than WMH-unconnected cortex over 12 months.

Discussion: Our results suggest that WMH may be associated with AD-intrinsic processes of degeneration, in addition to vascular mechanisms.

Highlights: We studied white matter hyperintensities (WMHs) and WMH-connected cortical changes. WMHs are associated with more severe regional cortical degeneration. Findings suggest WMHs may be associated with Alzheimer's disease-intrinsic processes of degeneration.

Keywords: Alzheimer’s disease; MRI; PET; cortical thickness; synaptic density; white matter hyperintensities.