Abstract WP489: Disrupted Functional and Structural Connectivity Within Default Mode Network Contribute to WMH Related Cognitive Impairment

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Lili Huang ◽  
Qing Ye ◽  
Xin Chen ◽  
Dan Yang ◽  
Ruomeng Qin ◽  
...  

Aims: The prevalence of white matter hyperintensities (WMH) rises dramatically with aging. Both the progression of WMH and default mode network (DMN) have been proven to be closely associated with cognitive function. Thus, we hypothesized that changes in functional connectivity (FC) and structural connectivity (SC) of the DMN contributed to WMH related cognitive impairment. Methods: A total of 116 subjects were enrolled from the Cerebral Small Vessel Disease Register in Drum Tower Hospital of Nanjing University, and were distributed across three categories according to Fazekas rating scale: WMH I(n=57), WMH II(n=34), and WMH III (n=25). The clinical and neuropsychological data were collected, and all participants underwent 3D T1 weighted images, T2 weighted images, 3D fluid attenuated inversion recovery (FLAIR) images, diffusion tensor images (DTI), and diffusion weighted imaging (DWI). The alterations of FC and SC within the DMN were further explored in these subjects. Results: The study found that age and hypertension were risk factors for WMH progression. Subjects with a larger WMH burden displayed higher DMN FC in the medial frontal gyrus (MFG), while lower DMN FC in the thalamus. After adjustment for age, gender, and education, the increasing FC between the MFG, posterior cingulate cortex (PCC), and ascending mean diffusivity (MD) of the white matter tracts between the hippocampus and PCC were independent indicators of worse performance in memory. Moreover, the decreasing FC between the thalamus, PCC, and ascending MD of the white matter tracts between the thalamus and PCC were independent risk factors for a slower processing speed. Conclusion: The changes in FC and SC within the DMN attributed to WMH progression were responsible for the cognitive impairment.

2021 ◽  
Author(s):  
Gwang-Won Kim ◽  
Kwangsung Park ◽  
Gwang-Woo Jeong

Abstract The incidence of Alzheimer’s disease (AD) has been increasing each year; however, few methods are available to identify the effects of treatment for AD. Defective hippocampus has been associated with mild cognitive impairment (MCI), an early stage of AD. However, the effect of donepezil treatment on hippocampus-related networks is unknown. The purpose of this study was to evaluate the hippocampal white matter (WM) connectivity following donepezil treatment in patients with MCI using probabilistic tractography, and to further determine the WM integrity and changes in brain volume. Magnetic resonance imaging and diffusion tensor imaging (DTI) data of patients with MCI before and after 6-month donepezil treatment were acquired. Volumes and DTI scalars of 11 regions of interest comprising the frontal and temporal cortices and subcortical regions were measured. Seed-based structural connectivity analyses were focused on the hippocampus. Compared with healthy controls, patients with MCI showed significantly decreased hippocampal volume and WM connectivity with the superior frontal gyrus, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the amygdala (p < 0.05, Bonferroni-corrected). After six months of donepezil treatment, patients with MCI showed increased hippocampal-inferior temporal gyrus (ITG) WM connectivity (p < 0.05, Bonferroni-corrected), which was normalized to the healthy control. These findings will be useful in developing theories to describe the etiology of MCI and the therapeutic role of anticholinesterases.


Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. e2244-e2255 ◽  
Author(s):  
Ian O. Bledsoe ◽  
Glenn T. Stebbins ◽  
Doug Merkitch ◽  
Jennifer G. Goldman

ObjectiveTo evaluate microstructural characteristics of the corpus callosum using diffusion tensor imaging (DTI) and their relationships to cognitive impairment in Parkinson disease (PD).MethodsSeventy-five participants with PD and 24 healthy control (HC) participants underwent structural MRI brain scans including DTI sequences and clinical and neuropsychological evaluations. Using Movement Disorder Society criteria, PD participants were classified as having normal cognition (PD-NC, n = 23), mild cognitive impairment (PD-MCI, n = 35), or dementia (PDD, n = 17). Cognitive domain (attention/working memory, executive function, language, memory, visuospatial function) z scores were calculated. DTI scalar values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were established for 5 callosal segments on a midsagittal plane, single slice using a topographically derived parcellation method. Scalar values were compared among participant groups. Regression analyses were performed on cognitive domain z scores and DTI metrics.ResultsParticipants with PD showed increased AD values in the anterior 3 callosal segments compared to healthy controls. Participants with PDD had significantly increased AD, MD, and RD in the anterior 2 segments compared to participants with PD-NC and most anterior segment compared to participants with PD-MCI. FA values did not differ significantly between participants with PD and participants with HC or among PD cognitive groups. The strongest associations for the DTI metrics and cognitive performance occurred in the most anterior and most posterior callosal segments, and also reflected fronto-striatal and posterior cortical type cognitive deficits, respectively.ConclusionsMicrostructural white matter abnormalities of the corpus callosum, as measured by DTI, may contribute to PD cognitive impairment by disrupting information transfer across interhemispheric and callosal–cortical projections.


2016 ◽  
Vol 29 (5) ◽  
pp. 793-803 ◽  
Author(s):  
Wen-wei Cao ◽  
Yao Wang ◽  
Quan Dong ◽  
Xue Chen ◽  
Yan-sheng Li ◽  
...  

ABSTRACTBackground:Cerebral small vessel disease (SVD) is the common cause of cognitive decline in the old population. MRI can be used to clarify its mechanisms. However, the surrogate markers of MRI for early cognitive impairment in SVD remain uncertain to date. We investigated the cognitive impacts of cerebral microbleeds (CMBs), diffusion tensor imaging (DTI), and brain volumetric measurements in a cohort of post-stroke non-dementia SVD patients.Methods:Fifty five non-dementia SVD patients were consecutively recruited and categorized into two groups as no cognitive impairment (NCI) (n = 23) or vascular mild cognitive impairment (VaMCI) (n = 32). Detailed neuropsychological assessment and multimodal MRI were completed.Results:The two groups differed significantly on Z scores of all cognitive domains (all p < 0.01) except for the language. There were more patients with hypertension (p = 0.038) or depression (p = 0.019) in the VaMCI than those in the NCI group. Multiple regression analysis of cognition showed periventricular mean diffusivity (MD) (β = −0.457, p < 0.01) and deep CMBs numbers (β = −0.352, p < 0.01) as the predictors of attention/executive function, which explained 45.2% of the total variance. Periventricular MD was the independent predictor for either memory (β = −0.314, p < 0.05) or visuo-spatial function (β = −0.375, p < 0.01); however, only small proportion of variance could be accounted for (9.8% and 12.4%, respectively). Language was not found to be correlated with any of the MRI parameters. No correlation was found between brain atrophic indices and any of the cognitive measures.Conclusion:Arteriosclerotic CMBs and periventricular white matter disintegrity seem to be independent MRI surrogated markers in the early stage of cognitive impairment in SVD.


2012 ◽  
Vol 3 (1) ◽  
Author(s):  
Cheuk Tang ◽  
Emily Eaves ◽  
Kristen Dams-O’Connor ◽  
Lap Ho ◽  
Eric Leung ◽  
...  

AbstractDiffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jennifer L. Robinson ◽  
Madhura Baxi ◽  
Jeffrey S. Katz ◽  
Paul Waggoner ◽  
Ronald Beyers ◽  
...  

2020 ◽  
Author(s):  
Yunglin Gazes ◽  
Jayant Sakhardande ◽  
Ashley Mensing ◽  
Qolamreza Razlighi ◽  
Ann Ohkawa ◽  
...  

AbstractThis study examined within-subject differences among three fluid abilities that decline with age: reasoning, episodic memory and processing speed, compared with vocabulary, a crystallized ability that is maintained with age. The data were obtained from the Reference Ability Neural Network (RANN) study from which 221 participants had complete behavioral data for all 12 cognitive tasks, three per ability, along with fMRI and diffusion weighted imaging data. We used fMRI task activation to guide white matter tractography, and generated mean percent signal change in the regions associated with the processing of each ability along with diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), for each cognitive ability. Qualitatively brain regions associated with vocabulary were more localized and lateralized to the left hemisphere whereas the fluid abilities were associated with brain activations that were more distributed across the brain and bilaterally situated. Using continuous age, we observed smaller correlations between MD and age for white matter tracts connecting brain regions associated with the vocabulary ability than that for the fluid abilities, suggesting that vocabulary white matter tracts were better maintained with age. Furthermore, after multiple comparisons correction, the mean percent signal change for the episodic memory showed positive associations with behavioral performance, and the associations between MD and percent signal change differed by age such that, when divided into three age groups to further explore this interaction, only the oldest age group show a significant negative correlation between the two brain measures. Overall, the vocabulary ability may be better maintained with age due to the more localized brain regions involved, which places smaller reliance on long distance white matter tracts for signal transduction. These results support the hypothesis that functional activation and white matter structures underlying the vocabulary ability contribute to the ability’s greater resistance against aging.


2021 ◽  
Author(s):  
Panlong Li ◽  
Qi Huang ◽  
Shiyu Ban ◽  
Yuan Qiao ◽  
Jing Wu ◽  
...  

Abstract Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by mutations in NOTCH3 gene is a hereditary cerebral small vessel disease, manifesting with stroke, cognitive impairment and mood disturbances. Functional or structural changes in the default mode network (DMN), which plays important roles in cognitive and mental maintenance, have been found in a number of neurological and mental diseases. However, it is still unclear whether DMN is altered in CADASIL patients.Methods: Multimodal imaging methods, including magnetic resonance imaging (MRI) and positron emission tomography (PET), were applied to evaluate the functional, structural and metabolic characteristics of DMN in 25 CADASIL patients and 42 healthy controls.Results: Compared to controls, CADASIL patients had decreased nodal efficiency and degree centrality of the dorsal medial prefrontal cortex and hippocampal formation within DMN. Structural MRI and diffusion tensor imaging (DTI) showed decreased gray matter volume and fiber tracks presented in the bilateral hippocampal formation. Meanwhile, PET imaging showed decreased metabolism within the whole DMN in CADASIL. Furthermore, correlation analyses showed that these nodal characteristics, gray matter volume, and metabolic signals of DMN were related to cognitive scores in CADASIL.Conclusions: Our results suggested that altered network characteristics of DMN may play important roles in cognitive deficits of CADASIL.


2021 ◽  
Vol 13 ◽  
Author(s):  
Stephanie Matijevic ◽  
Lee Ryan

Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54–92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.


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