Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer's disease pathology and neurodegeneration along the Alzheimer's disease continuum

Moody, Jason F.; Dean, Douglas C.; Kecskemeti, Steve; Blennow, Kaj; Zetterberg, Henrik; Kollmorgen, Gwendlyn; Suridjan, Ivonne; Wild, Norbert; Carlsson, Cynthia M.; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

doi:10.1002/dad2.12381

Cited by 12 publications

(8 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, our findings are similar to a study on MAP-MRI in hemodialysis patients ( 22 ). Supporting this, research on Alzheimer’s disease has indicated that a decreased NG value could be indicative of axonal loss and demyelination ( 31 ). Changes in axial (NGAx) and radial (NGRad) neurite density also indicate changes in NG ( 11 ).…”

Section: Discussionmentioning

confidence: 94%

Assessing brain microstructural changes in chronic kidney disease: a diffusion imaging study using multiple models

Han,

Yang,

Yuan

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

ObjectivesTo explore the effectiveness of diffusion quantitative parameters derived from advanced diffusion models in detecting brain microstructural changes in patients with chronic kidney disease (CKD).MethodsThe study comprised 44 CKD patients (eGFR<59 mL/min/1.73 m2) and 35 age-and sex-matched healthy controls. All patients underwent diffusion spectrum imaging (DSI) and conventional magnetic resonance imaging. Reconstructed to obtain diffusion MRI models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) and Mean Apparent Propagator (MAP)-MRI, were processed to obtain multi-parameter maps. The Tract-Based Spatial Statistics (TBSS) analysis was utilized for detecting microstructural differences and Pearson correlation analysis assessed the relationship between renal metabolism markers and diffusion parameters in the brain regions of CKD patients. Receiver operating characteristic (ROC) curve analysis assessed the diagnostic performance of diffusion models, with AUC comparisons made using DeLong’s method.ResultsSignificant differences were noted in DTI, NODDI, and MAP-MRI parameters between CKD patients and controls (p < 0.05). DTI indicated a decrease in Fractional Anisotropy(FA) and an increase in Mean and Radial Diffusivity (MD and RD) in CKD patients. NODDI indicated decreased Intracellular and increased Extracellular Volume Fractions (ICVF and ECVF). MAP-MRI identified extensive microstructural changes, with elevated Mean Squared Displacement (MSD) and Q-space Inverse Variance (QIV) values, and reduced Non-Gaussianity (NG), Axial Non-Gaussianity (NGAx), Radial Non-Gaussianity (NGRad), Return-to-Origin Probability (RTOP), Return-to-Axis Probability (RTAP), and Return-to-Plane Probability (RTPP). There was a moderate correlation between serum uric acid (SUA) and diffusion parameters in six brain regions (p < 0.05). ROC analysis showed the AUC values of DTI_FA ranged from 0.70 to 0.793. MAP_NGAx in the Retrolenticular part of the internal capsule R reported a high AUC value of 0.843 (p < 0.05), which was not significantly different from other diffusion parameters (p > 0.05).ConclusionThe advanced diffusion models (DTI, NODDI, and MAP-MRI) are promising for detecting brain microstructural changes in CKD patients, offering significant insights into CKD-affected brain areas.

show abstract

Section: Discussionmentioning

confidence: 94%

Assessing brain microstructural changes in chronic kidney disease: a diffusion imaging study using multiple models

Han,

Yang,

Yuan

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…In mild cognitive impairment, increased RD and MD, but not AxD, were found to be associated with low cognitive performance ( 81 , 82 ), representing a diffusion profile more suggestive of demyelination ( 83 ) and neurodegeneration ( 84 ). Prior research has shown a nonmonotonic trajectory of diffusion metrics in early AD, suggestive of an early inflammatory process followed by a neurodegenerative process ( 69–71 ).…”

Section: Discussionmentioning

confidence: 98%

Diffusion imaging markers of accelerated aging of the lower cingulum in subjective cognitive decline

Flaherty,

Sui,

Masurkar

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

IntroductionAlzheimer’s Disease (AD) typically starts in the medial temporal lobe, then develops into a neurodegenerative cascade which spreads to other brain regions. People with subjective cognitive decline (SCD) are more likely to develop dementia, especially in the presence of amyloid pathology. Thus, we were interested in the white matter microstructure of the medial temporal lobe in SCD, specifically the lower cingulum bundle that leads into the hippocampus. Diffusion tensor imaging (DTI) has been shown to differentiate SCD participants who will progress to mild cognitive impairment from those who will not. However, the biology underlying these DTI metrics is unclear, and results in the medial temporal lobe have been inconsistent.MethodsTo better characterize the microstructure of this region, we applied DTI to cognitively normal participants in the Cam-CAN database over the age of 55 with cognitive testing and diffusion MRI available (N = 325, 127 SCD). Diffusion MRI was processed to generate regional and voxel-wise diffusion tensor values in bilateral lower cingulum white matter, while T1-weighted MRI was processed to generate regional volume and cortical thickness in the medial temporal lobe white matter, entorhinal cortex, temporal pole, and hippocampus.ResultsSCD participants had thinner cortex in bilateral entorhinal cortex and right temporal pole. No between-group differences were noted for any of the microstructural metrics of the lower cingulum. However, correlations with delayed story recall were significant for all diffusion microstructure metrics in the right lower cingulum in SCD, but not in controls, with a significant interaction effect. Additionally, the SCD group showed an accelerated aging effect in bilateral lower cingulum with MD, AxD, and RD.DiscussionThe diffusion profiles observed in both interaction effects are suggestive of a mixed neuroinflammatory and neurodegenerative pathology. Left entorhinal cortical thinning correlated with decreased FA and increased RD, suggestive of demyelination. However, right entorhinal cortical thinning also correlated with increased AxD, suggestive of a mixed pathology. This may reflect combined pathologies implicated in early AD. DTI was more sensitive than cortical thickness to the associations between SCD, memory, and age. The combined effects of mixed pathology may increase the sensitivity of DTI metrics to variations with age and cognition.

show abstract

“…These approaches include bi-tensor free water models (such as Pasternak) and three-compartment models (such as neurite orientation dispersion and density imaging, NODDI). Markedly elevated free water levels have been associated with Parkinson's disease progression, multiple sclerosis degeneration and biomarkers of Alzheimer's disease [49][50][51]. Finally, WMH are seen in T2 fluid-attenuated inversion recovery (FLAIR) MRI and are considered to be representative of white matter gliosis and degeneration [52].…”

Section: Astrocyte Aqp4 Channels and Extracellular Free Watermentioning

confidence: 99%

Imaging the neurovascular unit in health and neurodegeneration: a scoping review of interdependencies between MRI measures

Rowsthorn,

Pham,

Nazem-Zadeh

et al. 2023

Fluids Barriers CNS

View full text Add to dashboard Cite

The neurovascular unit (NVU) is a complex structure that facilitates nutrient delivery and metabolic waste clearance, forms the blood–brain barrier (BBB), and supports fluid homeostasis in the brain. The integrity of NVU subcomponents can be measured in vivo using magnetic resonance imaging (MRI), including quantification of enlarged perivascular spaces (ePVS), BBB permeability, cerebral perfusion and extracellular free water. The breakdown of NVU subparts is individually associated with aging, pathology, and cognition. However, how these subcomponents interact as a system, and how interdependencies are impacted by pathology remains unclear. This systematic scoping review identified 26 studies that investigated the inter-relationships between multiple subcomponents of the NVU in nonclinical and neurodegenerative populations using MRI. A further 112 studies investigated associations between the NVU and white matter hyperintensities (WMH). We identify two putative clusters of NVU interdependencies: a ‘vascular’ cluster comprising BBB permeability, perfusion and basal ganglia ePVS; and a ‘fluid’ cluster comprising ePVS, free water and WMH. Emerging evidence suggests that subcomponent coupling within these clusters may be differentially related to aging, neurovascular injury or neurodegenerative pathology.

show abstract

Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer's disease pathology and neurodegeneration along the Alzheimer's disease continuum

Cited by 12 publications

References 65 publications

Assessing brain microstructural changes in chronic kidney disease: a diffusion imaging study using multiple models

Assessing brain microstructural changes in chronic kidney disease: a diffusion imaging study using multiple models

Diffusion imaging markers of accelerated aging of the lower cingulum in subjective cognitive decline

Imaging the neurovascular unit in health and neurodegeneration: a scoping review of interdependencies between MRI measures

Contact Info

Product

Resources

About