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  • 1
    Online Resource
    Online Resource
    Quantitative R1 in the locus coeruleus in Alzheimer’s disease dementia
    Wiley ; 2021
    In:  Alzheimer's & Dementia Vol. 17, No. S5 ( 2021-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S5 ( 2021-12)
    Abstract: Prior studies employing neuromelanin‐sensitive MRI have linked neurodegeneration in the locus coeruleus (LC) to Alzheimer’s disease (AD) pathology. MPnRAGE (Keckskemeti et al., 2016), a novel MRI technique developed at UW‐Madison, generates multiple inversion recovery contrasts and quantitative T1 relaxometry. Quantitative R1 (= 1/T1), the longitudinal relaxation rate, is sensitive to brain myelin, lipid, and iron content according to post‐mortem studies. As prior studies suggest altered quantitative R1 (QR1) among individuals with AD pathology, this imaging marker may be sensitive to AD‐associated pathology in the LC, one of the first regions in the brain to show signs of AD pathology (Braak et al., 2011). Here we performed preliminary assessments to test for differences in QR1 among individuals with and without clinical mild cognitive impairment (MCI‐AD), or AD dementia. We hypothesized that R1 would be lower among individuals with AD and MCI compared to unimpaired controls. Method Participants were enrolled in the Alzheimer’s Disease Connectome Project (ADCP) at UW‐Madison. 103 older adults diagnosed as cognitively unimpaired (N=53), MCI‐AD, and AD‐Dementia (Table 1) underwent MPnRAGE at a 1mm 3 resolution. MPnRAGE‐derived QR1 maps were registered to MNI space using SPM12. LC masks (from Betts et al., 2017) were transformed to subject space to extract mean R1 in the bilateral LC using the Marsbar toolbox. Multiple linear regression was run within Rstudio to investigate the relationships between age, R1, and diagnosis. The main effects of interest included age and diagnosis, as well as their interaction. Sex was included as a covariate. Result No significant associations were found between QR1 and age, diagnostic status, and their interaction. The main effect of age on R1 trended toward significance (p=0.059). Age trends are shown in Figure 1. Sex was not a significant covariate. Conclusion While QR1 was not significantly associated with age or clinical diagnosis within the LC, further research will evaluate the extent to which QR1 is altered among other regions affected by AD pathology. Further, R1 could be tested between groups stratified by AD biomarker status. Finally, the LC is a small structure, thus future work could also test R1 estimated at higher resolution.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v17.S5
    DOI: 10.1002/alz.054035
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 2
    Online Resource
    Online Resource
    Assessment of myelin in Alzheimer’s by a R1 and the relationship to amyloid burden
    Wiley ; 2023
    In:  Alzheimer's & Dementia Vol. 19, No. S3 ( 2023-06)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. S3 ( 2023-06)
    Abstract: Alzheimer’s disease (AD) is well known as a grey matter disorder, characterized by substantial and progressive neurodegeneration. However, less is known about myelin loss in AD, particularly as the disease progresses in severity. To gain a better insight on the role of myelin over the clinical and biologic progression of AD, we tested for differences in quantitative relaxometry R1, a metric sensitive to brain myelin, among individuals who were cognitively unimpaired (CU), diagnosed with mild cognitive impairment (MCI), and diagnosed with AD, in addition to testing for associations between R1 and amyloid PET. Understanding the course of myelin injury in disease progression is expected to address the gap in knowledge about the trajectory of myelin alterations in AD. Methods Participants from the Alzheimer’s Disease Connectome Project underwent T1‐weighted (T1w) MPnRAGE with motion‐correction and amyloid imaging with [11C]PiB PET. Composite T1w images and R1 maps were reconstructed at 1mm isotropic resolution. T1w scans were bias‐field corrected and denoised before undergoing tissue segmentation. R1 was sampled and bilaterally averaged across cortical‐adjacent white matter (WM). An average WM‐R1 was generated for each participant by calculating the mean of cortical regions R1. MANOVA and regression analyses were used to analyze the difference and relationship between each group’s WM‐R1 and PiB‐Index. Result The three groups showed an association with PiB‐Index and WM‐R1, Pillai’s Trace = 0.28, F(4, 110) = 4.56, p 〈 0.01. Participants with AD showed higher amyloid and lower WM‐R1. In contrast, UC and MCI participants showed lower amyloid and WM‐R1. A significant correlation was found in individuals with AD wherein amyloid burden was positively correlated with WM‐R1 across the whole brain, R 2 = 0.64, F(1, 6) = 10.99, p = 0.016. Conclusion Our findings indicate myelin differences by clinical status, in addition to relationships between amyloid and R1 indices of myelin. While AD was associated with lower myelin as indexed by R1, we unexpectedly found that higher cortical amyloid in AD was associated with higher myelin indexed by R1, suggesting an increase in myelination as AD progresses. Overall, lower myelin in clinical AD, accompanied by the higher myelin with greater amyloid burden suggests possible reparative mechanisms in response to neurodegeneration in AD.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v19.S3
    DOI: 10.1002/alz.063213
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2201940-6
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  • 3
    Online Resource
    Online Resource
    Higher cortical myelin is associated with worse performance on cognitive tests: Findings from the Alzheimer’s Disease Connectome Project
    Wiley ; 2022
    In:  Alzheimer's & Dementia Vol. 18, No. S5 ( 2022-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S5 ( 2022-12)
    Abstract: Brain myelin is known to play an important role in maintaining optimal neuronal function, with deficits in myelin leading to worse performance on cognitive tests. The extent to which cortex‐specific myelin is associated with other cognitive domains, or is impacted by disease processes such as Alzheimer’s disease (AD), is unknown. Here we leverage MPnRAGE‐derived quantitative R1 (Kecskemeti et al., 2016; 2018), a metric sensitive to brain myelin, to assess the role of intracortical myelin in performance on tests of executive function (exec_func), working memory (working_mem), and processing speed (process_speed) in older adults who ranged from cognitively unimpaired to those with dementia. Method 143 older adults (N=75 cognitively unimpaired, N=44 mild cognitive impairment, N=24 dementia) enrolled in the Alzheimer’s Disease Connectome Project underwent T1‐weighted (T1w) MPnRAGE MRI with motion‐correction and testing via the NIH Toolbox Cognitive Battery. Inherently registered quantitative R1 maps and T1w images were reconstructed at 1mm isotropic resolution. The image processing pipeline and composite regions of interest (ROIs) used for analysis can be viewed in Figure 1. Uncorrected standard scores were computed by the NIH Toolbox for each measure of exec_func (dimensional change card sort), working_mem (list sorting), and process_speed (pattern comparison). Multiple linear regression models were employed in R with test scores as the dependent variable, regional R1 as the predictor of interest, and age, sex, and education as covariates. Result Higher R1 was associated with worse exec_func in regions that are affected in AD, including posterior cingulate (ß = ‐62.47, t(1,138) = ‐2.42, p = 0.017) and temporal cortices(ß = ‐123.05, t(1,138) = ‐2.77, p = 0.0064) ROIs. Additionally, higher R1 in temporal cortices was associated with worse working_mem (ß = ‐158.16, t(1,133) = ‐2.84, p = 0.0053) (Figure 2). There were no significant associations between process_speed and regional cortical R1. Conclusion Unexpectedly, higher regional cortical myelin (as indexed by R1) was associated with worse exec_func and working_mem, suggesting higher R1 may be indicative of a regional pathologic process. Future work will test the interactive relationships between amyloid and/or tau pathology and cortical myelin on cognitive performance.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v18.S5
    DOI: 10.1002/alz.067930
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2201940-6
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