Arteriolosclerosis severity is linked to lower cortical volume in community-based older adults
Poster No:
186
Submission Type:
Abstract Submission
Authors:
Ana Tomash1, Md Tahmid Yasar1, David Bennett2, Julie Schneider2, Konstantinos Arfanakis2
Institutions:
1Illinois Institute of Technology, Chicago, IL, 2Rush University Medical Center, Chicago, IL
First Author:
Co-Author(s):
Introduction:
Brain arteriolosclerosis, characterized by thickened vessel walls and narrowed arterioles, is a key pathology of cerebral small vessel disease(Blevins et al., 2021). This condition has been linked to declines in cognitive and motor function(Buchman et al., 2013) and a higher risk of developing dementia(Arvanitakis et al., 2016). Despite its widespread and harmful effects, little is known about how arteriolosclerosis influences brain macrostructure. Therefore, this study aimed to investigate the association between brain arteriolosclerosis and in-vivo cortical and subcortical brain volumes in a large community-based cohort of older adults.
Methods:
Participants, MRI, neuropathology
The data was collected from 192 community-dwelling older adults participating in four longitudinal aging cohort studies(Bennett et al., 2018; L. Barnes et al., 2012) (the Rush Memory and Aging Project, Religious Orders Study, Minority Aging Research Study, and the Clinical Core of the Rush Alzheimer's Disease Research Center) (Fig. 1A). 3T MRI scanners were used to acquire in-vivo 3D whole-brain images with T1-weighted MPRAGE sequences (1×1×1 mm³). Subcortical and cortical brain volumes were segmented using multi-atlas segmentation(Kotrotsou et al., 2014) and then normalized by the intracranial volume. After a participant's death, the brain was extracted and examined by a board-certified neuropathologist. The assessed pathologies included arteriolosclerosis (Buchman et al., 2013), Alzheimer's pathology, Lewy bodies, limbic-predominant age-related TDP-43 encephalopathy (LATE-NC), gross and microscopic infarcts, atherosclerosis, hippocampal sclerosis, and cerebral amyloid angiopathy (Fig. 1B).
Statistical analysis
Linear regression was used to investigate the association of brain arteriolosclerosis with subcortical and cortical volumes (normalized by intracranial volume) controlling for all other neuropathologies (Fig. 1B), demographics (age at death, sex, years of education), antemortem intervals, and scanner (Fig. 1A). Statistical analysis was conducted using FSL's PALM tool, with 10,000 permutations. After correcting for multiple testing using the family-wise error rate (FWER) significance was set at p<0.05. Regions exhibiting significant associations were overlaid on the MIITRA atlas(Wu et al., 2023).
The data was collected from 192 community-dwelling older adults participating in four longitudinal aging cohort studies(Bennett et al., 2018; L. Barnes et al., 2012) (the Rush Memory and Aging Project, Religious Orders Study, Minority Aging Research Study, and the Clinical Core of the Rush Alzheimer's Disease Research Center) (Fig. 1A). 3T MRI scanners were used to acquire in-vivo 3D whole-brain images with T1-weighted MPRAGE sequences (1×1×1 mm³). Subcortical and cortical brain volumes were segmented using multi-atlas segmentation(Kotrotsou et al., 2014) and then normalized by the intracranial volume. After a participant's death, the brain was extracted and examined by a board-certified neuropathologist. The assessed pathologies included arteriolosclerosis (Buchman et al., 2013), Alzheimer's pathology, Lewy bodies, limbic-predominant age-related TDP-43 encephalopathy (LATE-NC), gross and microscopic infarcts, atherosclerosis, hippocampal sclerosis, and cerebral amyloid angiopathy (Fig. 1B).
Statistical analysis
Linear regression was used to investigate the association of brain arteriolosclerosis with subcortical and cortical volumes (normalized by intracranial volume) controlling for all other neuropathologies (Fig. 1B), demographics (age at death, sex, years of education), antemortem intervals, and scanner (Fig. 1A). Statistical analysis was conducted using FSL's PALM tool, with 10,000 permutations. After correcting for multiple testing using the family-wise error rate (FWER) significance was set at p<0.05. Regions exhibiting significant associations were overlaid on the MIITRA atlas(Wu et al., 2023).
·Figure 1
Results:
Higher severity of brain arteriolosclerosis was linked to lower volume in the middle temporal gyrus, independent of demographics and other neuropathologies (Figs. 2A, 2C). The abnormality in the volume of the middle temporal gyrus started with mild arteriolosclerosis and became more significant for moderate and severe arteriolosclerosis (Fig. 2B). These findings build on prior studies, which primarily associated arteriolosclerosis with white matter hyperintensities(Arfanakis et al., 2020). This large community-based study highlights a clear link between arteriolosclerosis and temporal lobe neurodegeneration.
·Figure 2
Conclusions:
Using in-vivo MRI and detailed neuropathology, this study revealed that brain arteriolosclerosis is associated with lower volume in the middle temporal gyrus, independent of other vascular or neurodegenerative pathologies. This novel association improves understanding of arteriolosclerosis's brain impact and could serve as an additional feature to improve ARTS(Makkinejad et al., 2021), a recently developed in-vivo marker of arteriolosclerosis, enhancing its accuracy in predicting the pathology.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Lifespan Development:
Aging 2
Keywords:
Aging
Cerebrovascular Disease
MRI
Neurological
Other - Dementia; Alzheimer's disease; Hypertension
1|2Indicates the priority used for review
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Provide references using APA citation style.
Arvanitakis, Z., et al (2016). Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: A cross-sectional study. The Lancet Neurology, 15(9), 934–943.
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Blevins, B. L., et al (2021). Brain arteriolosclerosis. Acta Neuropathologica, 141(1), 1–24.
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Kotrotsou, A., et al (2014). Ex vivo MR volumetry of human brain hemispheres. Magnetic Resonance in Medicine, 71(1), 364–374.
L. Barnes, et al (2012). The Minority Aging Research Study: Ongoing Efforts to Obtain Brain Donation in African Americans without Dementia. Current Alzheimer Research, 9(6), 734–745.
Makkinejad, N., et al (2021). ARTS: A novel In-vivo classifier of arteriolosclerosis for the older adult brain. NeuroImage: Clinical, 31, 102768.
Winkler, A. M., et al (2014). Permutation inference for the general linear model. NeuroImage, 92, 381–397.
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