Altered Superficial White Matter on Tractography MRI in Alzheimer's Disease

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.

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Plasma P-tau181 levels reflects white matter microstructural changes across Alzheimer’s disease progression

10.21203/rs.3.rs-115316/v3 ◽

2021 ◽

Author(s):

Fardin Nabizadeh ◽

Seyed Behnamedin Jameie ◽

Saghar Khani ◽

Aida Rezaei ◽

Fatemeh Ranjbaran ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Behavioral Problems ◽

Structural Changes ◽

Diffusion Tensor ◽

Cognitive Impairments ◽

Mean Diffusivity ◽

Diagnostic Procedures ◽

Microstructural Changes

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.

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

10.1101/2021.05.07.21256728 ◽

2021 ◽

Author(s):

Thomas Veale ◽

Ian B Malone ◽

Teresa Poole ◽

Thomas D Parker ◽

Catherine F Slattery ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Fractional Anisotropy ◽

Diffusion Mri ◽

Grey Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Young Onset ◽

Neurite Density

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.

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The use of diffusion-tensor imaging to assess microstructural integrity of white matter of patients with Alzheimer’s disease

Journal of radiology and nuclear medicine ◽

10.20862/0042-4676-2018-99-6-295-304 ◽

2019 ◽

Vol 99 (6) ◽

pp. 295-304

Author(s):

V. A. Perepelov ◽

V. I. Solodovnikov ◽

V. E. Sinitsyn ◽

E. M. Perepelova ◽

N. N. Koberskaya ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Posterior Part ◽

Mean Diffusivity ◽

Imaging Protocol ◽

Microstructural Integrity

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.

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Application of diffusion tensor imaging in Alzheimer’s disease: quantification of white matter microstructural changes

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00460-x ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Shereen Magdy Abdel Malak Esrael ◽

Ahmed Mostafa Mohamed Hamed ◽

Eman M. Khedr ◽

Radwa Kamel Soliman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Healthy Subjects ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Elderly Subjects ◽

Potential Biomarker ◽

The Right

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.

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IC-P-091: Diffusion Tensor MRI in Preclinical Alzheimer's Disease: Decreased Fractional Anisotropy in Parahippocampal White Matter in MCI and Older Adults with Cognitive Complaints

Alzheimer s & Dementia ◽

10.1016/j.jalz.2010.05.105 ◽

2010 ◽

Vol 6 ◽

pp. S37-S38 ◽

Cited By ~ 2

Author(s):

Yang Wang ◽

John D. West ◽

Laura A. Flashman ◽

Heather A. Wishart ◽

Laura A. Rabin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

White Matter ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Diffusion Tensor Mri ◽

Cognitive Complaints ◽

Preclinical Alzheimer’S Disease

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Abstract 44: Associations of Atrial Fibrillation, Neuroimaging Measures of Cerebrovascular Disease and Alzheimer’S Disease-related Pathology, and Cognitive Impairment

Stroke ◽

10.1161/str.46.suppl_1.44 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Jonathan Graff-Radford ◽

Rosebud Roberts ◽

Malini Madhavan ◽

Alejandro Rabinstein ◽

Ruth Cha ◽

...

Keyword(s):

Atrial Fibrillation ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

White Matter ◽

Cerebrovascular Disease ◽

Regression Models ◽

Grey Matter ◽

White Matter Hyperintensity ◽

Carrier Status

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.

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Automatic determination of white matter hyperintensity properties in relation to the development of Alzheimer's disease

10.1117/12.2216369 ◽

2016 ◽

Author(s):

Sandra van der Velden ◽

Christoph Moenninghoff ◽

Isabel Wanke ◽

Martha Jokisch ◽

Christian Weimar ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

White Matter Hyperintensity ◽

Automatic Determination

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Verbal memory and hippocampal volume predict subsequent fornix microstructure in those at risk for Alzheimer’s disease

Brain Imaging and Behavior ◽

10.1007/s11682-019-00183-8 ◽

2019 ◽

Vol 14 (6) ◽

pp. 2311-2322 ◽

Cited By ~ 1

Author(s):

Junhong Yu ◽

◽

Tatia M. C. Lee

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Verbal Memory ◽

Structural Equation ◽

Structural Equation Models ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Hippocampal Atrophy ◽

Cross Sectional ◽

Mci Due To Ad

Abstract While strong cross-sectional evidence supported the use of fornix microstructure as a marker for detecting Alzheimer’s disease (AD), longitudinal data remains inconclusive on the sequential nature of fornix microstructure abnormalities and AD progression. An unequivocal longitudinal relationship between fornix microstructure and markers of AD progression –memory impairment and hippocampal atrophy, must be established to validate fornix microstructure as a marker of AD progression. We included 115 participants from the Alzheimer’s Disease Neuroimaging Initiative across the non-demented AD spectrum— defined as those who had at least one AD risk marker at baseline (e.g., mild cognitive impairment (MCI) due to AD diagnosis, amyloid or ApoE4 positivity) and/or ‘cognitively normal individuals who converted to MCI due to AD or AD, with structural and diffusion tensor imaging scans at baseline and two years follow-up. Hippocampal volumes (HV), fractional anisotropy (FA) and mean diffusivity (MD) in the fornix were extracted. Memory was indexed via composite scores of verbal memory tests. Structural equation models tested the bidirectional cross-lagged effects of fornix microstructure, memory, and HV. Impaired memory and smaller HV at baseline significantly predicted worse fornix microstructure (decreased FA and increased MD) two years later. Baseline fornix microstructure was not associated with subsequent changes in memory and HV. Fornix microstructure is compromised likely at a later stage, where significant decline in memory and hippocampal atrophy have occurred. This limits the utility of fornix microstructure in the early detection of AD. Our findings inform the possible pathophysiology and refined the use of AD neural markers.

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