Brain arteriolosclerosis linked to lower gray matter volume in elderly community-cohort
Poster No:
209
Submission Type:
Abstract Submission
Authors:
Ana Tomash1, Mahir Tazwar1, Md Tahmid Yasar1, David Bennett2, Julie Schneider2, Konstantinos Arfanakis1,2
Institutions:
1Illinois Institute of Technology, Chicago, IL, 2Rush University Medical Center, Chicago, IL
First Author:
Co-Author(s):
Konstantinos Arfanakis
Illinois Institute of Technology|Rush University Medical Center
Chicago, IL|Chicago, IL
Illinois Institute of Technology|Rush University Medical Center
Chicago, IL|Chicago, IL
Introduction:
Brain arteriolosclerosis, characterized by thickening of vessel walls and arteriolar stenosis, is one of the key pathologies of cerebral small vessel disease[4]. It is linked to lower cognitive and motor function[5], and an increased risk of dementia[2]. Despite its prevalence and detrimental effects, the impact of arteriolosclerosis on brain macrostructure remains unexplored. Therefore, this study aimed to investigate the association of brain arteriolosclerosis with regional gray matter volumes in a large number of community-based older adults.
Methods:
Participants, MRI, neuropathology
A combination of ex-vivo MRI and detailed neuropathological evaluation of 882 older adults participating in four longitudinal, clinical-pathologic cohort studies of aging were included[3, 8]: Rush Memory and Aging Project (MAP), Religious Orders Study (ROS), Minority Aging Research Study (MARS), and Clinical Core (CC) of the Rush Alzheimer's Disease Research Center (Fig. 1A). Cerebral hemispheres were obtained at autopsy and imaged ex-vivo with a multi-echo spin-echo (ME-SE) sequence on 3T clinical MRI scanners about one-month postmortem[1]. The acquired voxel size was 0.6mm × 0.6mm × 1.5mm, and the scan time was approximately 30 minutes[1]. Gray and white matter segmentation was performed on the ex-vivo MRI data, and gray matter was subdivided into 42 cortical and subcortical regions using multi-atlas segmentation[7]. The volume of each region was measured and normalized by the participant's cerebral hemisphere volume[6]. Following ex-vivo MRI, all hemispheres underwent detailed neuropathologic examination. The assessed pathologies included arteriolosclerosis[5], atherosclerosis, cerebral amyloid angiopathy, gross and microscopic infarcts, Alzheimer's pathology, Lewy bodies, limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC), and hippocampal sclerosis (Fig. 1B).
Statistical analysis
Linear regression was used to investigate the association of brain arteriolosclerosis with regional gray matter volumes (normalized by cerebral hemisphere volume) controlling for all other neuropathologies (Fig. 1B), demographics (age at death, sex, years of education), postmortem intervals, and scanner (Fig. 1A). Statistical analysis was conducted using FSL's PALM tool, with 10,000 permutations. After false discovery rate (FDR) correction for multiple testing, significance was set at p<0.05.
A combination of ex-vivo MRI and detailed neuropathological evaluation of 882 older adults participating in four longitudinal, clinical-pathologic cohort studies of aging were included[3, 8]: Rush Memory and Aging Project (MAP), Religious Orders Study (ROS), Minority Aging Research Study (MARS), and Clinical Core (CC) of the Rush Alzheimer's Disease Research Center (Fig. 1A). Cerebral hemispheres were obtained at autopsy and imaged ex-vivo with a multi-echo spin-echo (ME-SE) sequence on 3T clinical MRI scanners about one-month postmortem[1]. The acquired voxel size was 0.6mm × 0.6mm × 1.5mm, and the scan time was approximately 30 minutes[1]. Gray and white matter segmentation was performed on the ex-vivo MRI data, and gray matter was subdivided into 42 cortical and subcortical regions using multi-atlas segmentation[7]. The volume of each region was measured and normalized by the participant's cerebral hemisphere volume[6]. Following ex-vivo MRI, all hemispheres underwent detailed neuropathologic examination. The assessed pathologies included arteriolosclerosis[5], atherosclerosis, cerebral amyloid angiopathy, gross and microscopic infarcts, Alzheimer's pathology, Lewy bodies, limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC), and hippocampal sclerosis (Fig. 1B).
Statistical analysis
Linear regression was used to investigate the association of brain arteriolosclerosis with regional gray matter volumes (normalized by cerebral hemisphere volume) controlling for all other neuropathologies (Fig. 1B), demographics (age at death, sex, years of education), postmortem intervals, and scanner (Fig. 1A). Statistical analysis was conducted using FSL's PALM tool, with 10,000 permutations. After false discovery rate (FDR) correction for multiple testing, significance was set at p<0.05.
Results:
Severe brain arteriolosclerosis was associated with lower gray matter volume in regions like medial orbitofrontal, superior frontal, pericalcarine, cuneus, and lateral occipital areas, independently of the effects of other neuropathologies (Fig. 2). No regions exhibited higher volume with more severe arteriolosclerosis. These findings significantly expand our understanding of arteriolosclerosis-related brain anomalies, challenging its presumed association mainly with white matter hyperintensities[1]. The present work in a large number of community-based older adults provides strong evidence that arteriolosclerosis is also related to neurodegenerative changes in gray matter. Furthermore, the brain regions involved are distributed in both the anterior and posterior parts of the brain in line with the more widespread distribution of arteriolosclerosis pathology in the brain.
Conclusions:
By combining ex-vivo MRI and detailed neuropathological examination in a large number of community-based older adults this study demonstrated that brain arteriolosclerosis is associated with lower volume in several gray matter regions. The findings were independent of the effects of other vascular or neurodegenerative pathologies. Hence, this discovery enhances our understanding of the impact of arteriolosclerosis on the brain.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Lifespan Development:
Aging 2
Keywords:
Aging
MRI
Neurological
Other - Dementia; Alzheimer's disease; Hypertension
1|2Indicates the priority used for review
Provide references using author date format
[2] 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 (Aug. 2016), 934–943.
[3] Bennett, D.A. et al. 2018. Religious Orders Study and Rush Memory and Aging Project. Journal of Alzheimer’s Disease. 64, s1 (Jun. 2018), S161–S189.
[4] Blevins, B.L. et al. 2021. Brain arteriolosclerosis. Acta Neuropathologica. 141, 1 (Jan. 2021), 1–24.
[5] Buchman, A.S. et al. 2013. Microvascular brain pathology and late-life motor impairment. Neurology. 80, 8 (Feb. 2013), 712–718.
[6] Dawe, R.J. et al. 2011. Neuropathologic Correlates of Hippocampal Atrophy in the Elderly: A Clinical, Pathologic, Postmortem MRI Study. PLoS ONE. 6, 10 (Oct. 2011), e26286.
[7] Kotrotsou, A. et al. 2014. Ex vivo MR volumetry of human brain hemispheres. Magnetic Resonance in Medicine. 71, 1 (Jan. 2014), 364–374.
[8] L. Barnes, L. et al. 2012. The Minority Aging Research Study: Ongoing Efforts to Obtain Brain Donation in African Americans without Dementia. Current Alzheimer Research. 9, 6 (Jun. 2012), 734–745.
[9] Makkinejad, N. et al. 2021. ARTS: A novel In-vivo classifier of arteriolosclerosis for the older adult brain. NeuroImage: Clinical. 31, (2021), 102768.
[10] Wu, Y. et al. 2023. High resolution 0.5mm isotropic T1-weighted and diffusion tensor templates of the brain of non-demented older adults in a common space for the MIITRA atlas. NeuroImage. 282, (Nov. 2023), 120387.