Tract‐specific white matter hyperintensities disrupt neural network function in Alzheimer's disease

Abstract

Introduction White matter hyperintensities (WMHs) increase the risk of Alzheimer’s disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. Method Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts’ projection areas within the default mode network (DMN). Results WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. Conclusions High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.

Age‐dependent amyloid deposition is associated with white matter alterations in cognitively normal adults during the adult life span

“…White matter hyperintensities (as defined by the standards for reporting vascular changes on neuroimaging (STRIVE) criteria) 43 were segmented based on FLAIR MRI scans, using a semiautomated method that was described previously 44 . (For a more detailed description see supplementary methods.)…”

White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease

“…Thus, it is possible that vascular and amyloid deposition are synergistically involved in Alzheimer’s disease and contribute to white matter alterations. Higher levels of white matter alterations are associated with FDG-PET decline ( Lo et al , 2012 ; Glodzik et al , 2014 ; Marnane et al , 2016 ), higher grey matter atrophy ( Bos et al , 2017 ), reduced functional network integrity ( Taylor et al , 2017 ) and worse cognitive decline ( Lo et al , 2012 ; Marchant et al , 2012 ; Vemuri et al , 2015 ). Thus, white matter alterations, possibly stemming from cerebrovascular disease, may add to the effects of amyloid deposition on neurodegeneration and cognition in ageing and Alzheimer’s disease.…”

Aberrant White Matter Microstructure as a Potential Diagnostic Marker in Alzheimer’s Disease by Automated Fiber Quantification

“…Analysis of the white matter microstructure in preclinical phases of AD has revealed that the cognitively normal elderly with positive Aβ-42 show increased DA in the left IFOF compared to the aged with negative Aβ-42 [37]. Moreover, the macroscopic research of white matter injury in AD also provided the evidence that the volume of white matter hyperintensity within IFOF was the highest among all ber tracts and correlated with decreased functional connectivity in IFOFconnected areas of default mode network [38]. Therefore, the above ndings indicated that left-sided white matter microstructural integrity in the ber tract level may be more vulnerable and the left IFOF may be a potential biomarker for the early identi cation of AD.…”