Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States
ß-amyloid (Aß) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here we explored potential re...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-02-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00015/full |
| _version_ | 1817983998057512960 |
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| author | Yang eJiang Yang eJiang Yang eJiang Haiqing eHuang Erin eAbner Erin eAbner Lucas S Broster Lucas S Broster Gregory eJicha Gregory eJicha Frederick A Schmitt Frederick A Schmitt Richard eKryscio Richard eKryscio Anders eAndersen Anders eAndersen David ePowell David ePowell Linda eVan Eldik Linda eVan Eldik Brian T Gold Brian T Gold Brian T Gold Peter T Nelson Charles eSmith Charles eSmith Charles eSmith Mingzhou eDing |
| author_facet | Yang eJiang Yang eJiang Yang eJiang Haiqing eHuang Erin eAbner Erin eAbner Lucas S Broster Lucas S Broster Gregory eJicha Gregory eJicha Frederick A Schmitt Frederick A Schmitt Richard eKryscio Richard eKryscio Anders eAndersen Anders eAndersen David ePowell David ePowell Linda eVan Eldik Linda eVan Eldik Brian T Gold Brian T Gold Brian T Gold Peter T Nelson Charles eSmith Charles eSmith Charles eSmith Mingzhou eDing |
| author_sort | Yang eJiang |
| collection | DOAJ |
| description | ß-amyloid (Aß) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here we explored potential relationships between functional connectivity patterns within the default-mode network (DMN), age, CSF biomarkers (Aß42 and pTau181) and cognitive status in older adults. Multiple measures of functional connectivity were explored including a novel time series based measure (Total Interdependence; TI). In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aß42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of functional connectivity in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults. |
| first_indexed | 2024-04-13T23:39:32Z |
| format | Article |
| id | doaj.art-14d57e2bf6154368b8e6a9d133fae6f5 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T23:39:32Z |
| publishDate | 2016-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-14d57e2bf6154368b8e6a9d133fae6f52022-12-22T02:24:33ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652016-02-01810.3389/fnagi.2016.00015174794Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task StatesYang eJiang0Yang eJiang1Yang eJiang2Haiqing eHuang3Erin eAbner4Erin eAbner5Lucas S Broster6Lucas S Broster7Gregory eJicha8Gregory eJicha9Frederick A Schmitt10Frederick A Schmitt11Richard eKryscio12Richard eKryscio13Anders eAndersen14Anders eAndersen15David ePowell16David ePowell17Linda eVan Eldik18Linda eVan Eldik19Brian T Gold20Brian T Gold21Brian T Gold22Peter T Nelson23Charles eSmith24Charles eSmith25Charles eSmith26Mingzhou eDing27University of KentuckyUniveristy of KentuckyUniversity of KentuckyUniversity of FloridaUniveristy of KentuckyUniversity of Kentucky College of Public HealthUniversity of KentuckyUniveristy of KentuckyUniveristy of KentuckyUniversity of Kentucky College of MedicineUniveristy of KentuckyUniversity of Kentucky College of MedicineUniveristy of KentuckyUniversity of KentuckyUniversity of Kentucky College of MedicineUniversity of KentuckyUniversity of Kentucky College of MedicineUniversity of KentuckyUniveristy of KentuckyUniversity of Kentucky College of MedicineUniveristy of KentuckyUniversity of Kentucky College of MedicineUniversity of KentuckyUniveristy of KentuckyUniveristy of KentuckyUniversity of Kentucky College of MedicineUniversity of KentuckyUniversity of Floridaß-amyloid (Aß) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here we explored potential relationships between functional connectivity patterns within the default-mode network (DMN), age, CSF biomarkers (Aß42 and pTau181) and cognitive status in older adults. Multiple measures of functional connectivity were explored including a novel time series based measure (Total Interdependence; TI). In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aß42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of functional connectivity in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults.http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00015/fullCerebrospinal FluidCSF biomarkersdefault-mode network (DMN)Aß42 peptidesß-amyloidCognitive status |
| spellingShingle | Yang eJiang Yang eJiang Yang eJiang Haiqing eHuang Erin eAbner Erin eAbner Lucas S Broster Lucas S Broster Gregory eJicha Gregory eJicha Frederick A Schmitt Frederick A Schmitt Richard eKryscio Richard eKryscio Anders eAndersen Anders eAndersen David ePowell David ePowell Linda eVan Eldik Linda eVan Eldik Brian T Gold Brian T Gold Brian T Gold Peter T Nelson Charles eSmith Charles eSmith Charles eSmith Mingzhou eDing Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States Frontiers in Aging Neuroscience Cerebrospinal Fluid CSF biomarkers default-mode network (DMN) Aß42 peptides ß-amyloid Cognitive status |
| title | Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States |
| title_full | Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States |
| title_fullStr | Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States |
| title_full_unstemmed | Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States |
| title_short | Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States |
| title_sort | alzheimer s biomarkers are correlated with brain connectivity in older adults differentially during resting and task states |
| topic | Cerebrospinal Fluid CSF biomarkers default-mode network (DMN) Aß42 peptides ß-amyloid Cognitive status |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00015/full |
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