Tau-related white-matter alterations along spatially selective pathways

Risacher, Shannon L.; Xie, Linhui; Li, Junjie; Harezlak, Jaroslaw; Farlow, Martin R.; Unverzagt, Frederick W.; Gao, Sujuan; Apostolova, Liana G.; Saykin, Andrew J.; Wu, Yu‐Chien

doi:10.1016/j.neuroimage.2020.117560

Cited by 36 publications

(42 citation statements)

References 58 publications

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“…In the amyloid-positive participants, the authors observed significant negative correlations between ICVF and 18 F-THK5351 and between ODI and 18 F-THK5351, mainly in the bilateral mesial and lateral temporal lobes ( Figure 5 ), suggesting that tau and neuroinflammation in AlzD might reduce neurite density and orientation dispersion. Wen et al [ 86 ] also found a high degree of association between the GM tau-PET signal and WM integrity measured by DTI and NODDI metrics ( Figure 6 ). In line with Braak staging in AlzD, the spatial association pattern was initiated from the medial temporal lobe and developed posteriorly to the occipital brain regions and superiorly and anteriorly to the parietal and frontal lobes.…”

Section: Applications Of Advanced Diffusion Mri Techniques In Neurodegenerative Diseasesmentioning

confidence: 77%

“…“Direction of change” denotes the direction of change in the diffusion metric in the setting of increased tau-PET signal in adjacent regions of interest in the gray matter. Abbreviations; AD, axial diffusivity; DTI, diffusion tensor imaging; FA, fractional anisotropy; ICVF, intracellular volume fraction; iter, iteration; MD, mean diffusivity; NODDI, neurite orientation dispersion and density imaging; ODI, orientation dispersion index; PET, positron emission tomography; RD, radial diffusivity (adapted and reproduced with permission from Wen et al [ 86 ]).…”

Section: Figurementioning

confidence: 99%

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Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

Kamagata

Andica

Kato

et al. 2021

IJMS

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There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.

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Section: Applications Of Advanced Diffusion Mri Techniques In Neurodegenerative Diseasesmentioning

confidence: 77%

Section: Figurementioning

confidence: 99%

Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

Kamagata

Andica

Kato

et al. 2021

IJMS

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“…In contrast, temporal WM tracts may not only aid in the spreading of tau [ 14 ] but are progressively damaged because of increasing local tau toxicity [ 15 ]. Two tracts that are of particular interest in the context of tau are the parahippocampal cingulum bundle (commonly referred to as CGH – cingulum adjoining the hippocampus) [ 14 ] and inferior temporal WM (ITWM) [ 16 ]. The CGH WM tract is the primary connection with the hippocampus which is one of the earliest regions of tau deposition.…”

Section: Introductionmentioning

confidence: 99%

White matter damage due to vascular, tau, and TDP-43 pathologies and its relevance to cognition

Raghavan

Przybelski

Reid

et al. 2022

acta neuropathol commun

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Multi-compartment modelling of white matter microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) can provide information on white matter health through neurite density index and free water measures. We hypothesized that cerebrovascular disease, Alzheimer’s disease, and TDP-43 proteinopathy would be associated with distinct NODDI readouts of white matter damage which would be informative for identifying the substrate for cognitive impairment. We identified two independent cohorts with multi-shell diffusion MRI, amyloid and tau PET, and cognitive assessments: specifically, a population-based cohort of 347 elderly randomly sampled from the Olmsted county, Minnesota, population and a clinical research-based cohort of 61 amyloid positive Alzheimer’s dementia participants. We observed an increase in free water and decrease in neurite density using NODDI measures in the genu of the corpus callosum associated with vascular risk factors, which we refer to as the vascular white matter component. Tau PET signal reflective of 3R/4R tau deposition was associated with worsening neurite density index in the temporal white matter where we measured parahippocampal cingulum and inferior temporal white matter bundles. Worsening temporal white matter neurite density was associated with (antemortem confirmed) FDG TDP-43 signature. Post-mortem neuropathologic data on a small subset of this sample lend support to our findings. In the community-dwelling cohort where vascular disease was more prevalent, the NODDI vascular white matter component explained variability in global cognition (partial R2 of free water and neurite density = 8.3%) and MMSE performance (8.2%) which was comparable to amyloid PET (7.4% for global cognition and 6.6% for memory). In the AD dementia cohort, tau deposition was the greatest contributor to cognitive performance (9.6%), but there was also a non-trivial contribution of the temporal white matter component (8.5%) to cognitive performance. The differences observed between the two cohorts were reflective of their distinct clinical composition. White matter microstructural damage assessed using advanced diffusion models may add significant value for distinguishing the underlying substrate (whether cerebrovascular disease versus neurodegenerative disease caused by tau deposition or TDP-43 pathology) for cognitive impairment in older adults. Graphical abstract

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“…The presence of AD pathology may not strongly affect the preoperative FA and MD values in patients with iNPH. Although recent DTI studies have reported tau-related white matter alterations in patients with mild cognitive impairment or AD, severe changes in brain white matter integrity by ventricular dilation may obscure white matter alterations due to the presence of AD pathology in patients with iNPH [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Reduced default mode network connectivity relative to white matter integrity is associated with poor cognitive outcomes in patients with idiopathic normal pressure hydrocephalus

et al. 2021

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Background The aim of this study was to investigate whether default mode network (DMN) connectivity and brain white matter integrity at baseline were associated with severe cognitive impairments at baseline and poor cognitive outcomes after shunt placement in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods Twenty consecutive patients with iNPH whose symptoms were followed for 6 months after shunt placement and 10 healthy controls (HCs) were enrolled. DMN connectivity and brain white matter integrity at baseline in the patients with iNPH and HCs were detected by using resting-state functional magnetic resonance imaging (MRI) with independent component analysis and diffusion tensor imaging, respectively, and these MRI indexes were compared between the patients with iNPH and HCs. Performance on neuropsychological tests for memory and executive function and on the gait test was assessed in the patients with iNPH at baseline and 6 months after shunt placement. We divided the patients with iNPH into the relatively preserved and reduced DMN connectivity groups using the MRI indexes for DMN connectivity and brain white matter integrity, and the clinical measures were compared between the relatively preserved and reduced DMN connectivity groups. Results Mean DMN connectivity in the iNPH group was significantly lower than that in the HC group and was significantly positively correlated with Rey auditory verbal learning test (RAVLT) immediate recall scores and frontal assessment battery (FAB) scores. Mean fractional anisotropy of the whole-brain white matter skeleton in the iNPH group was significantly lower than that in the HC group. The reduced DMN connectivity group showed significantly worse performance on the RAVLT at baseline and significantly worse improvement in the RAVLT immediate recall and recognition scores and the FAB scores than the preserved DMN connectivity group. Moreover, the RAVLT recognition score highly discriminated patients with relatively preserved DMN connectivity from those with relatively reduced DMN connectivity. Conclusions Our findings indicated that iNPH patients with reduced DMN connectivity relative to the severity of brain white matter disruption have severe memory deficits at baseline and poorer cognitive outcomes after shunt placement. However, further larger-scale studies are needed to confirm these findings.

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Tau-related white-matter alterations along spatially selective pathways

Cited by 36 publications

References 58 publications

Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

White matter damage due to vascular, tau, and TDP-43 pathologies and its relevance to cognition

Reduced default mode network connectivity relative to white matter integrity is associated with poor cognitive outcomes in patients with idiopathic normal pressure hydrocephalus

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