Distinct fiber-specific white matter reductions pattern in early- and late-onset Alzheimer’s disease

Xiao Luo,Dan Wu,Qingze Zeng,Chao Wang,Kaicheng Li,Yeerfan Jiaerken,Peiyu Huang,Shuyue Wang,Minming Zhang,Xiaopei Xu,Ruiting Zhang

doi:10.18632/aging.202702

Abstract

Background: The underlying white matter impairment in patients with early and late-onset Alzheimer’s disease (EOAD and LOAD) is still unclear, and this might due to the complex AD pathology.Methods: We included 31 EOAD, 45 LOAD, and 64 younger, 46 elder controls in our study to undergo MRI examinations. Fiber density (FD) and fiber bundle cross-section (FC) were measured using fixel-based analysis based on diffusion weighted images. On whole brain and tract-based level, we compared these parameters among different groups (p<0.05, FWE corrected). Moreover, we verified our results in another independent dataset using the same analyses.Results: Compared to young healthy controls, EOAD had significantly lower FD in the splenium of corpus callosum, limbic tracts, cingulum bundles, and posterior thalamic radiation, and higher FC in the splenium of corpus callosum, dorsal cingulum and posterior thalamic radiation. On the other hand, LOAD had lower FD and FC as well. Importantly, a similar pattern was found in the independent validation dataset. Among all groups, both the FD and FC were associated with cognitive function. Furthermore, FD of fornix column and body, and FC of ventral cingulum were associated with composite amyloid and tau level (r=-0.34 and -0.53, p<0.001) respectively.Conclusions: EOAD and LOAD were characterized by distinct white matter impairment patterns, which may be attributable to their different neuropathologies.

Highlights

Early-onset Alzheimer’s disease (EOAD) has more domain cognitive deficits and worse prognosis than late-onset Alzheimer’s disease (LOAD)
LOAD had comparable fiber density (FD) and fiber bundle cross-section (FC) decrease, centered to the splenium of CC (SCC), cingulum bundles, and posterior association tracts. Both EOAD and LOAD had a similar decrease in FDC, mainly involving the cingulum bundle
Distinct white matter (WM) damage in EOAD and LOAD might account for different cognitive pictures

Summary

Introduction

Early-onset Alzheimer’s disease (EOAD) has more domain cognitive deficits and worse prognosis than late-onset Alzheimer’s disease (LOAD). We used the recently established method, fixel-based analysis (FBA), to investigate fiber-specific white matter (WM) reduction patterns in EOAD and LOAD. According to the onset age (65 years), we could further divide AD into early- and late-onset Alzheimer’s disease (EOAD/LOAD) [2]. Apart from memory deficit, EOAD tends to have worse performance in attention, visuospatial skills, and executive functions [4, 5]. Both EOAD and LOAD share the same neuropathological hallmarks but present distinct deposition patterns [6, 7]. Multiple studies have reported that EOAD patients show higher burdens of amyloid deposition and NFTs than LOAD in frontal and parietal lobes [8,9,10]

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Results

Conclusion