scholarly journals Loss and Reorganisation of Superficial White Matter in Alzheimer's disease: A Diffusion MRI study

Author(s):  
Thomas Veale ◽  
Ian B Malone ◽  
Teresa Poole ◽  
Thomas D Parker ◽  
Catherine F Slattery ◽  
...  

Pathological involvement of cerebral white matter in Alzheimer's disease has been shown using diffusion tensor imaging. Superficial white matter (SWM) changes have been relatively understudied despite their importance in cortico-cortical connections. Measuring SWM degeneration using diffusion tensor imaging is challenging due to its complex structure and proximity to the cortex. To overcome this we investigated diffusion MRI changes in young-onset Alzheimer's disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are due to degeneration (e.g. loss of myelinated fibres) and those due to reorganisation (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer's disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, the grey/white boundary, SWM (1mm below grey/white boundary) and SWM/deeper white matter (2mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants' diffusion metrics along the cortical profile. The SWM of young-onset Alzheimer's disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P<0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P<0.05). Young-onset Alzheimer's disease individuals had lower fractional anisotropy in the SWM of two regions (entorhinal and parahippocampus) (both P<0.05) and higher fractional anisotropy within the postcentral region (P<0.05). Mean diffusivity in SWM was higher in the young-onset Alzheimer's disease group in the parahippocampal region (P<0.05) and lower in three regions (postcentral, precentral and superior temporal) (all P<0.05). In the overlying grey matter, disease-related changes were largely consistent with SWM findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity SWM changes. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer's disease individuals (all P<0.001) but group differences reduced in magnitude and coverage when moving towards the SWM. These results show that microstructural changes occur within SWM and along the cortical profile in individuals with young-onset Alzheimer's disease. Lower neurite density and higher orientation dispersion suggests underlying SWM fibres undergo neurodegeneration and reorganisation, two effects previously indiscernible using standard diffusion tensor metrics in SWM.

2018 ◽  
Author(s):  
Farshid Sepehrband ◽  
Ryan P Cabeen ◽  
Jeiran Choupan ◽  
Giuseppe Barisano ◽  
Meng Law ◽  
...  

AbstractDiffusion tensor imaging (DTI) has been extensively used to map changes in brain tissue related to neurological disorders. Among the most widespread DTI findings are increased mean diffusivity and decreased fractional anisotropy of white matter tissue in neurodegenerative diseases. Here we utilize multi-shell diffusion imaging to separate diffusion signal of the brain parenchyma from fluid within the white matter. We show that unincorporated anisotropic water in perivascular space (PVS) significantly, and systematically, biases DTI measures, casting new light on the biological validity of many previously reported findings. Despite the challenge this poses for interpreting these past findings, our results suggest that multi-shell diffusion MRI provides a new opportunity for incorporating the PVS contribution, ultimately strengthening the clinical and scientific value of diffusion MRI.HighlightsPerivascular space (PVS) fluid significantly contributes to diffusion tensor imaging metricsIncreased PVS fluid results in increased mean diffusivity and decreased fractional anisotropyPVS contribution to diffusion signal is overlooked and demands further investigation


2021 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Seyed Behnamedin Jameie ◽  
Saghar Khani ◽  
Aida Rezaei ◽  
Fatemeh Ranjbaran ◽  
...  

Abstract Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties that hinder daily activities and lead to personal and behavioral problems. Plasma hyperphosphorylated tau protein at threonine 181 (p-tau181), a blood-based biomarker, has recently emerged as a new tool with sufficient sensitivity for distinguishing AD patients from healthy people. We herein investigated the association of plasma P-tau181 and white matter (WM) microstructural changes in AD. We examined data from a large prospective cohort of elderly individuals participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) which covers a wide clinical spectrum from normal cognition to AD dementia with measurements of plasma P-tau181 and imaging findings at baseline. A subset of 41 patients with AD, 119 patients with mild cognitive impairments (MCI), and 43 healthy controls (HC) were included in the study, all of whom had baseline blood P-tau181 levels and had also undergone Diffusion Tensor Imaging (DTI). The analysis revealed that the plasma level of P-tau181 have positive correlation with changes in Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AxD), but a negative with Fractional Anisotropy (FA) parameters in WM regions of all participants. There is also a significant association between WM microstructural changes in different regions and P-tau181 plasma measurements within each MCI, HC and AD group. In conclusion, our findings clarified that plasma P-tau181 levels are associated with changes in WM integrity in AD. P-tau181 could improve the accuracy of diagnostic procedures and support the application of blood-based biomarkers to diagnose WM neurodegeneration. Longitudinal clinical studies are also needed to demonstrate the efficacy of the P-tau181 biomarker and predict its role in structural changes.


2019 ◽  
Vol 99 (6) ◽  
pp. 295-304
Author(s):  
V. A. Perepelov ◽  
V. I. Solodovnikov ◽  
V. E. Sinitsyn ◽  
E. M. Perepelova ◽  
N. N. Koberskaya ◽  
...  

Objective. To compare diffusion-tensor imaging (DTI) measures in different anatomic regions of the brain in patients with an isolated Alzheimer's disease (AD) and patients with AD and small-vessel disease (SVD).Material and methods. 20 AD patients, aged 66 (±10), of whom 11 AD patients had an isolated neurodegenerative process and 9 patients, who were diagnosed with AD+SVD, were examined. A research was made on a 3 T Siemens Magnetom Skyra MR-scanner. All participants underwent the same imaging protocol, which included standard clinical- and diffusion tensor pulse sequences. With an MR-image processing software package Olea Medical Sphere 3.0, fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity (AxD and RxD) were measured in different brain regions.Results. Significant differences in DTI measures (FA, MD, AxD, RxD), indicating more severe white matter microstructural damage in AD+SVD patients, compared with patients with an isolated AD, were observed in middle thalamic radiation, upper and lower longitudinal bundles, posterior part of cingulate gyrus and genu of corpus callosum.Conclusion. DTI is an informative method, highly sensitive in detecting difference in white matter microstructural integrity of brain tissue in individuals with an isolated AD and patients with AD+SVD.


2016 ◽  
Vol 6 (2) ◽  
pp. 233-241 ◽  
Author(s):  
William Reginold ◽  
Angela C. Luedke ◽  
Justine Itorralba ◽  
Juan Fernandez-Ruiz ◽  
Omar Islam ◽  
...  

Background/Aims: Superficial white matter provides extensive cortico-cortical connections. This tractography study aimed to assess the diffusion characteristics of superficial white matter tracts in Alzheimer's disease. Methods: Diffusion tensor 3T magnetic resonance imaging scans were acquired in 24 controls and 16 participants with Alzheimer's disease. Neuropsychological test scores were available in some participants. Tractography was performed by the Fiber Assignment by Continuous Tracking (FACT) method. The superficial white matter was manually segmented and divided into frontal, parietal, temporal and occipital lobes. The mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AxD) and fractional anisotropy (FA) of these tracts were compared between controls and participants with Alzheimer's disease and correlated with available cognitive tests while adjusting for age and white matter hyperintensity volume. Results: Alzheimer's disease was associated with increased MD (p = 0.0011), increased RD (p = 0.0019) and increased AxD (p = 0.0017) in temporal superficial white matter. In controls, superficial white matter was associated with the performance on the Montreal Cognitive Assessment, Stroop and Trail Making Test B tests, whereas in Alzheimer's disease patients, it was not associated with the performance on cognitive tests. Conclusion: Temporal lobe superficial white matter appears to be disrupted in Alzheimer's disease.


Author(s):  
Shereen Magdy Abdel Malak Esrael ◽  
Ahmed Mostafa Mohamed Hamed ◽  
Eman M. Khedr ◽  
Radwa Kamel Soliman

Abstract Background Alzheimer’s disease (AD) is the most common cause of dementia in the aging population, responsible for 60–70% of all demented cases. Diffusion tensor imaging (DTI) is a very recent technique that allows the mapping of white matter (WM) microstructure changes in neurological disorders. The current study was conducted to compare DTI parameters between AD patients and healthy elderly subjects and to determine whether DTI can act as a potential biomarker for AD. Results There were significant differences in Modified Mini-Mental State Examination (MMMSE) and Clinical Dementia Rating (CDR) between the two groups. As regards the DTI parameters, significant differences were found between AD patients versus healthy subjects, in the mean diffusivity (MD) of the splenium [(1.05 ± 0.19) vs. (0.92 ± 0.22) , P=0.03], the MD of the right uncinate fasciculus [(0.92 ± 0.04) vs. (0.87 ± 0.05), P= 0.01],  and MD of the right arcuate fasciculus (AF) [(0.83 ± 0.04) vs. (0.79 ± 0.04) P =0.01],  as well as the MD of the right and left inferior fronto-occipital fasiculus (IFOF) [(0.89 ± 0.06) vs. (0.83 ± 0.04), P=0.01]. In addition, there were significant differences in the fractional anisotropy (FA) of the right and left cingulum between both groups [(0.45 ± 0.02) vs. (0.47 ± 0.03), P=0.01 and (0.45 ± 0.03) vs. 0.49± 0.04), P=0.01, respectively]. The overall accuracy of the aforementioned parameters ranged between 73 and 81% with the MD of the left cingulum revealing the highest accuracy. Conclusion DTI proofed to be a useful tool in differentiating AD patients from healthy subjects. In our study, we found that the splenium, cingulum, IFOF, and the right UF and right AF are the main tracts involved in AD. The left cingulum provided the highest accuracy in differentiating AD from normal subjects.


Author(s):  
James R. Hall ◽  
Leigh A. Johnson ◽  
Fan Zhang ◽  
Melissa Petersen ◽  
Arthur W. Toga ◽  
...  

<b><i>Introduction:</i></b> Alzheimer’s disease (AD) is the most frequently occurring neurodegenerative disease; however, little work has been conducted examining biomarkers of AD among Mexican Americans. Here, we examined diffusion tensor MRI marker profiles for detecting mild cognitive impairment (MCI) and dementia in a multi-ethnic cohort. <b><i>Methods:</i></b> 3T MRI measures of fractional anisotropy (FA) were examined among 1,636 participants of the ongoing community-based Health &amp; Aging Brain among Latino Elders (HABLE) community-based study (Mexican American <i>n</i> = 851; non-Hispanic white <i>n</i> = 785). <b><i>Results:</i></b> The FA profile was highly accurate in detecting both MCI (area under the receiver operating characteristic curve [AUC] = 0.99) and dementia (AUC = 0.98). However, the FA profile varied significantly not only between diagnostic groups but also between Mexican Americans and non-Hispanic whites. <b><i>Conclusion:</i></b> Findings suggest that diffusion tensor imaging markers may have a role in the neurodiagnostic process for detecting MCI and dementia among diverse populations.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jonathan Graff-Radford ◽  
Rosebud Roberts ◽  
Malini Madhavan ◽  
Alejandro Rabinstein ◽  
Ruth Cha ◽  
...  

The objective of this study was to investigate the cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer’s disease-related pathology, and their interaction with cognitive impairment. MRI scans of non-demented individuals (n=1044) from the population-based Mayo Clinic Study of Aging were analyzed for infarctions, total grey matter, hippocampal and white matter hyperintensity volumes. A subset of 496 individuals underwent FDG and C-11 Pittsburgh compound B (PiB) PET scans. We assessed the associations of atrial fibrillation with i) categorical MRI measures (cortical and subcortical infarctions) using multivariable logistic regression models, and with ii) continuous MRI measures ( hippocampal, total grey matter, and white matter hyperintensity volumes) and FDG-PET and PiB-PET measures using multivariable linear regression models, and adjusting for confounders. Among participants who underwent MRI (median age, 77.8, 51.6% male), 13.5% had atrial fibrillation. Presence of atrial fibrillation was associated with subcortical infarctions (odds ratio [OR], 1.83; p=0.002), cortical infarctions (OR, 1.91; p=0.03), total grey matter volume (Beta [β], -.025, p<.0001) after controlling for age, education, gender, APOE e4 carrier status, coronary artery disease, diabetes, history of clinical stroke, and hypertension. However, atrial fibrillation was not associated with white matter hyperintensity volume, hippocampal volume, Alzheimer’s pattern of FDG hypometabolism or PiB uptake. There was a significant interaction of cortical infarction (p for interaction=0.004) and subcortical infarction (p for interaction =0.015) with atrial fibrillation with regards to odds of mild cognitive impairment (MCI). Using subjects with no atrial fibrillation and no infarction as the reference, the OR (95% confidence intervals [CI]) for MCI was 2.98 (1.66, 5.35;p = 0.0002) among participants with atrial fibrillation and any infarction, 0.69 (0.36, 1.33;p= 0.27) for atrial fibrillation and no infarction, and 1.50 (0.96, 2.32;p = 0.07) for no atrial fibrillation and any infarction. These data highlight that atrial fibrillation is associated with MCI in the presence of infarctions.


Neurology ◽  
2018 ◽  
Vol 92 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Meher R. Juttukonda ◽  
Giulia Franco ◽  
Dario J. Englot ◽  
Ya-Chen Lin ◽  
Kalen J. Petersen ◽  
...  

ObjectiveTo assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.MethodsSedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.ResultsFractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body (p < 0.01), sagittal stratum (p = 0.01), forceps major (p = 0.02), pontine crossing tract (p = 0.03), and retrolenticular internal capsule (p = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle (p < 0.01), middle cerebellar peduncle (p = 0.05), and inferior cerebellar peduncle (p = 0.05).ConclusionsRegionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.


2018 ◽  
Vol 32 (1) ◽  
pp. 10-16
Author(s):  
Alexander Rau ◽  
Elias Kellner ◽  
Niels A Foit ◽  
Niklas Lützen ◽  
Dieter H Heiland ◽  
...  

The aim of this study was to evaluate whether ganglioglioma (GGL), dysembryoplastic neuroepithelial tumour (DNET) and FCD (focal cortical dysplasia) are distinguishable through diffusion tensor imaging. Additionally, it was investigated whether the diffusion measures differed in the perilesional (pNAWM) and in the contralateral normal appearing white matter (cNAWM). Six GGLs, eight DNETs and seven FCDs were included in this study. Quantitative diffusion measures, that is, axial, radial and mean diffusivity and fractional anisotropy, were determined in the lesion identified on isotropic T2 or FLAIR-weighted images and in pNAWM and cNAWM, respectively. DNET differed from FCD in mean diffusivity, and GGL from FCD in radial diffusivity. Both types of glioneuronal tumours were different from pNAWM in fractional anisotropy and radial diffusivity. For identifying the tumour edges, threshold values for tumour-free tissue were investigated with receiver operating characteristic analyses: tumour could be separated from pNAWM at a threshold ≤ 0.32 (fractional anisotropy) or ≥ 0.56 (radial diffusivity) *10–3 mm2/s (area under the curve 0.995 and 0.990 respectively). While diffusion parameters of FCDs differed from cNAWM (radial diffusivity (*10–3 mm/s2): 0.74 ± 0.19 vs. 0.43 ± 0.05; corrected p-value < 0.001), the pNAWM could not be differentiated from the FCD.


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