Dataset Information

Alzheimer's Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States.

ABSTRACT: ?-amyloid (A?) 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 (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (A?42 and pTau181), and cognitive status in older adults. Multiple measures of FC 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 A?42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC 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 A?42 and A?42/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 A?42-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 A? and pTau burden in cognitively normal older adults.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC4744860 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Alzheimer's Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States.

Jiang Yang Y Huang Haiqing H Abner Erin E Broster Lucas S LS Jicha Gregory A GA Schmitt Frederick A FA Kryscio Richard R Andersen Anders A Powell David D Van Eldik Linda L Gold Brian T BT Nelson Peter T PT Smith Charles C Ding Mingzhou M

Frontiers in aging neuroscience 20160208

β-amyloid (Aβ) 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 (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ42 and pTau181), and cognitive status in older adults. Multiple measures of FC ...[more]

PMID: 26903858

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Project description:IntroductionNon-standard visuomotor integration requires the interaction of large networks in the brain. Previous findings have shown that non-standard visuomotor performance is impaired in individuals with specific dementia risk factors (family history of dementia and presence of the APOE ε4 allele) in advance of any cognitive impairments. These findings suggest that visuomotor impairments are associated with early dementia-related brain changes. The current study examined the underlying resting state functional connectivity (RSFC) associated with impaired non-standard visuomotor performance, as well as the impacts of dementia family history, sex, and APOE status.MethodsCognitively healthy older adults (n = 48) were tested on four visuomotor tasks where reach and gaze were increasingly spatially dissociated. Participants who had a family history of dementia or the APOE ε4 allele were considered to be at an increased risk for AD. To quantify RSFC within networks of interest, an EPI sequence sensitive to BOLD contrast was collected. The networks of interest were the default mode network (DMN), somatomotor network (SMN), dorsal attention network (DAN), ventral attention network (VAN), and frontoparietal control network (FPN).ResultsIndividuals with the ε4 allele showed abnormalities in RSFC between posterior DMN nodes that predicted poorer non-standard visuomotor performance. Specifically, multiple linear regression analyses revealed lower RSFC between the precuneus/posterior cingulate cortex and the left inferior parietal lobule as well as the left parahippocampal cortex. Presence of the APOE ε4 allele also modified the relationship between mean DAN RSFC and visuomotor control, where lower mean RSFC in the DAN predicted worse non-standard visuomotor performance only in APOE ε4 carriers. There were otherwise no effects of family history, APOE ε4 status, or sex on the relationship between RSFC and visuomotor performance for any of the other resting networks.ConclusionThe preliminary findings provide insight into the impact of APOE ε4-related genetic risk on neural networks underlying complex visuomotor transformations, and demonstrate that the non-standard visuomotor task paradigm discussed in this study may be used as a non-invasive, easily accessible assessment tool for dementia risk.

Dataset Information

Alzheimer's Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States.

Publications

Alzheimer's Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States.

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