Pathology-based and functional connectivity of affective symptoms in Alzheimer's disease continuum
Poster No:
191
Submission Type:
Abstract Submission
Authors:
Taein Lee1, Yong Jeong1
Institutions:
1Korea Advanced Institute of Science & Technology, Daejeon, Republic of Korea
First Author:
Co-Author:
Introduction:
Neuropsychiatric symptoms (NPS) are prevalent along the Alzheimer's disease continuum and can be one of the important factors related to the patients and their caregivers' quality of life. There have been various studies on NPS with different modalities, however, only a few investigated the NPS in the aspect of combining the molecular level with the whole-brain functional level information. Here, we aimed to explain NPS, mainly focusing on affective symptoms, with the relationship between the different levels of neuronal representation.
Methods:
We used preprocessed positron emission tomography (PET) images with AV-1451 and AV-45, resting-state functional magnetic resonance imaging (rsfMRI), T1, and clinical datasets such as neuropsychiatric inventory (NPI) scores of 74 amyloid-positive subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI) site. NPS were measured with NPI and grouped with 4 factors including affective symptoms. The score of affective symptoms was determined as the sum of the product of frequency and severity scores in depression and anxiety. Subjects with over zero scores of affective symptoms were classified into the group with affective symptoms (AS, n =25), and subjects with zero scores were classified into the group without affective symptoms (nAS, n = 49).
To minimize the signal distortion from each region-of-interest (ROI) during normalization, all the neuroimages were coregistered to individual structural T1 image which was parcellated and annotated by Freesurfer with Desikan-Killany-Tourville atlas. Amyloid and tau deposition were measured with the standardized uptake value ratio (SUVR) after applying partial volume correction. Resting-state fMRI was preprocessed along realignment, slice timing correction, outlier detection, and smoothing.
The ROIs with more burden of both tau and amyloid in AS were found through t-test or Mann-Whitney U test and determined as seeds. Then, functional connectivity (FC) between the pathological seed and voxel from the rest part of the brain was compared between the groups with age, education, the mini-mental state examination (MMSE) score, and sex as covariates. Lastly, a generalized linear model (GLM) for the severity of affective symptoms was conducted with significant FC and SUVR of two pathologies in the seed region.
To minimize the signal distortion from each region-of-interest (ROI) during normalization, all the neuroimages were coregistered to individual structural T1 image which was parcellated and annotated by Freesurfer with Desikan-Killany-Tourville atlas. Amyloid and tau deposition were measured with the standardized uptake value ratio (SUVR) after applying partial volume correction. Resting-state fMRI was preprocessed along realignment, slice timing correction, outlier detection, and smoothing.
The ROIs with more burden of both tau and amyloid in AS were found through t-test or Mann-Whitney U test and determined as seeds. Then, functional connectivity (FC) between the pathological seed and voxel from the rest part of the brain was compared between the groups with age, education, the mini-mental state examination (MMSE) score, and sex as covariates. Lastly, a generalized linear model (GLM) for the severity of affective symptoms was conducted with significant FC and SUVR of two pathologies in the seed region.
Results:
Twenty-three regions along temporal to part of frontal cortex showed more AD pathological burden in AS than in nAS (p < 0.05). Among these regions, the right middle temporal gyrus was negatively connected with parts of the left supramarginal and angular gyrus in AS (voxel threshold, p <0.001 (p-uncorrected, two-sided); cluster threshold, p < 0.05 (cluster-size p-FWE corrected)). FC between these regions became more negative as affective symptoms got more severe after considering the interaction between tau and amyloid in the right middle temporal gyrus.
Conclusions:
In our study, the NPS of the AS group showed a negative correlation with the FC between the rMTG, heavily affected by amyloid and tau deposition, and the left inferior parietal lobule (lIPL). Considering that rMTG is geometrically close to the suggested hub for tau propagation to the neocortex facilitated by amyloid-tau interactions, the pathological collapse of surrounding regions of the hub can be associated with affective symptoms. In addition, this rMTG is known to react to self-related negative stimuli, and lIPL, the negatively connected region with rMTG associated with affective symptoms, is included in emotion regulation. Therefore, through multi-modal imaging analysis at different levels, our study suggests that the change of FC of the AD pathologically damaged region is associated with affective symptoms in the AD continuum.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 2
PET Modeling and Analysis
Keywords:
FUNCTIONAL MRI
Positron Emission Tomography (PET)
Other - Functional connectivity; Alzheimer's Disease; Neuropsychiatric symptom
1|2Indicates the priority used for review
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