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

2019 ◽  
Vol 14 (6) ◽  
pp. 2311-2322 ◽  
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.

Do Worries About Cognitive Functioning and Concerns About Developing Alzheimer’s Disease Affect Psychological Well-Being?

2016 ◽  
Vol 29 (8) ◽  
pp. 1271-1287 ◽  
Author(s):  
Stephen J. Cutler ◽  
Corina Brăgaru
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Functioning ◽  
Structural Equation ◽  
Older Persons ◽  
Structural Equation Models ◽  
Well Being ◽  
Psychological Well Being ◽  
Lagged Effects

Objective: The objective of this study is to determine if cognitive worries affect psychological well-being, if these effects are long-term, and if such concerns affect well-being more so among persons with a parent having Alzheimer’s disease (AD). Method: We used structural equation models with three waves of data collected from persons ages 40 to 60 at T1. We created summative scores on five indicators of concerns about cognitive functioning and worries about dementia. Well-being measures included depression, life satisfaction, stress, and mastery. Results: We found (a) cognitive worries at Waves 1, 2, and 3 were generally associated with lower levels of psychological well-being at each of these waves; (b) there was no evidence of long-term, lagged effects, and (c) these relationships were statistically similar across groups of adult children and controls. Discussion: Because concerns about cognitive functioning and developing AD are pervasive among middle-aged and older persons, practitioners should be aware of their potentially deleterious effect on psychological well-being.

scholarly journals Plasma neurofilament light and cerebrospinal fluid biomarkers are associated with white matter damage in Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Balabandian ◽  
Mohammad Reza Rostami ◽  
Samuel Berchi Kankam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Microstructural Changes ◽  
Cerebrospinal Fluid Biomarkers

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration largely, and synaptic damage in AD. However, there is no investigation of the association between plasma NFL and white matter microstructure integrity. we have investigated the cross-sectional associations of plasma NFL, CSF tau, p tau, and Aβ with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, CSF total tau, CSF p tau, and as well as CSF Aβ, separately using a partial correlation model controlled for the effect of age, sex and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL has a negative correlation with FA and positive correlation with RD, AD, and MD values in different regions. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and for MCI progression to AD.

scholarly journals Detection of gray matter microstructural changes in Alzheimer’s disease continuum using fiber orientation

2020 ◽  
Author(s):  
Peter Lee ◽  
Hang-Rai Kim ◽  
Yong Jeong ◽  
Alzheimer's Disease Neuroimaging Initiative
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Gray Matter ◽  
Fiber Orientation ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
High Sensitivity ◽  
Normal Vector

Abstract Background This study aimed to investigate feasible gray matter microstructural biomarkers with high sensitivity for early Alzheimer’s disease (AD) detection. We propose a diffusion tensor imaging (DTI) measure, “radiality”, as an early AD biomarker. It is the dot product of the normal vector of the cortical surface and primary diffusion direction, which reflects the fiber orientation within the cortical column. Methods We analyzed neuroimages from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, including images from 78 cognitively normal (CN), 50 early mild cognitive impairment (EMCI), 34 late mild cognitive impairment (LMCI), and 39 AD patients. We then evaluated the cortical thickness (CTh), mean diffusivity (MD), which are conventional AD magnetic resonance imaging (MRI) biomarkers, and the amount of accumulated amyloid and tau using positron emission tomography (PET). Radiality was projected on the gray matter surface to compare and validate the changes with different stages alongside other neuroimage biomarkers.Results The results revealed decreased radiality primarily in the entorhinal, insula, frontal, and temporal cortex with further progression of disease. In particular, radiality could delineate the difference between the CN and EMCI groups, while the other biomarkers could not. We examined the relationship between radiality and other biomarkers to validate its pathological evidence in AD. Overall, radiality showed a high association with conventional biomarkers. Additional ROI analysis revealed the dynamics of AD-related changes as stages onward.Conclusion Radiality in cortical gray matter showed AD-specific changes and relevance with other conventional AD biomarkers with high sensitivity. Moreover, radiality could identify the group differences seen in EMCI, representative of changes in early AD, which supports its superiority in early diagnosis compared to that possible with conventional biomarkers. We provide evidence of structural changes with cognitive impairment and suggest radiality as a sensitive biomarker for identifying early AD.

scholarly journals Altered Volume and Structural Connectivity of the Hippocampus in Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Feng Feng ◽  
Weijie Huang ◽  
Qingqing Meng ◽  
Weijun Hao ◽  
Hongxiang Yao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Diffusion Tensor ◽  
Structural Connectivity ◽  
Hippocampal Volume ◽  
Brain Regions ◽  
Amnestic Mild Cognitive Impairment ◽  
Hippocampal Atrophy

Background: Hippocampal atrophy is a characteristic of Alzheimer’s disease (AD). However, alterations in structural connectivity (number of connecting fibers) between the hippocampus and whole brain regions due to hippocampal atrophy remain largely unknown in AD and its prodromal stage, amnestic mild cognitive impairment (aMCI).Methods: We collected high-resolution structural MRI (sMRI) and diffusion tensor imaging (DTI) data from 36 AD patients, 30 aMCI patients, and 41 normal control (NC) subjects. First, the volume and structural connectivity of the bilateral hippocampi were compared among the three groups. Second, correlations between volume and structural connectivity in the ipsilateral hippocampus were further analyzed. Finally, classification ability by hippocampal volume, its structural connectivity, and their combination were evaluated.Results: Although the volume and structural connectivity of the bilateral hippocampi were decreased in patients with AD and aMCI, only hippocampal volume correlated with neuropsychological test scores. However, positive correlations between hippocampal volume and ipsilateral structural connectivity were displayed in patients with AD and aMCI. Furthermore, classification accuracy (ACC) was higher in AD vs. aMCI and aMCI vs. NC by the combination of hippocampal volume and structural connectivity than by a single parameter. The highest values of the area under the receiver operating characteristic (ROC) curve (AUC) in every two groups were all obtained by combining hippocampal volume and structural connectivity.Conclusions: Our results showed that the combination of hippocampal volume and structural connectivity (number of connecting fibers) is a new perspective for the discrimination of AD and aMCI.

scholarly journals Plasma neurofilament light is associated with white matter damage in Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Balabandian ◽  
Mohammad Reza Rostami ◽  
Samuel Berchi Kankam ◽  
Fetemeh Ranjbaran ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Diffusion Tensor ◽  
Amyloid Β ◽  
Brain Regions ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Microstructural Changes

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration, and synaptic damage in AD. However, few investigations have been carried out on the association between plasma NFL and white matter microstructure integrity. We have investigated the cross-sectional associations of plasma NFL, CSF total tau, phosphorylated tau, and Amyloid β with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, separately using a partial correlation model controlled for the effect of age, sex, and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL negatively correlates with FA and the positive correlation with RD, DA, and MD values in different regions. Our findings showed that plasma NFL is associated with white matter changes and AD-related features, including atrophy and hypometabolism. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and MCI progression to AD.

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

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.

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

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.

Impaired Frontolimbic Connectivity and Depressive Symptoms in Patients with Alzheimer's Disease

2016 ◽  
Vol 41 (5-6) ◽  
pp. 281-291 ◽  
Author(s):  
Qingyong Zhu ◽  
Meiqing Lin ◽  
Siwei Bi ◽  
Zhiyan Ni ◽  
Jiuhan Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Cingulum Bundle ◽  
Fiber Tracts ◽  
Underlying Mechanisms ◽  
Microstructural Integrity ◽  
Myelin Injury

Background/Aims: Depressive symptoms are commonly observed in Alzheimer's disease (AD). The underlying mechanisms of depressive symptoms in AD remain unclear; frontolimbic circuitry dysfunction may play a role. We aimed to investigate the microstructural integrity of frontolimbic connectivity of specific fiber tracts in AD patients with and without depressive symptoms using diffusion tensor imaging (DTI). Methods: Eleven AD patients with depressive symptoms (dep-AD), 18 AD patients without depressive symptoms (nondep-AD), and 18 normal control (NC) subjects were included. The cingulum bundle (CB), uncinate fasciculus (UF), and fornix, mainly frontolimbic connectivity, were measured by DTI tractography and the metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) were calculated. Results: Compared with NC subjects, both dep-AD and nondep-AD patients showed significant differences for all indices in the fornix and significantly decreased FA and increased MD and RD in the bilateral CB and UF. When compared to nondep-AD patients, dep-AD patients showed significantly increased MD and RD in the bilateral CB and right UF. Conclusion: Depressive symptoms in AD patients may be involved in greater microstructural abnormalities of frontolimbic connectivity and myelin injury in the bilateral CB and right UF might contribute to the pathophysiology of depressive symptoms in AD.

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

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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