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Mary K Kramer¹, Peyton L Delgorio¹, Alexa M Diano¹, Olivia M Bailey¹, Grace McIlvain¹, Kyra E Twohy², Matthew Overstreet³, David G Edwards³, Christopher R Martens³, and Curtis L Johnson^1,2
1Biomedical Engineering, University of Delaware, Newark, DE, United States, ²Mechanical Engineering, University of Delaware, Newark, DE, United States, ³Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States

Keywords: Alzheimer's Disease, Elastography

Magnetic resonance elastography (MRE) is a robust and sensitive tool used to measure brain mechanical properties that can accurately detect improvements in brain health and function. Exercise and aerobic fitness levels are strongly tied to these brain mechanical properties and their related functionality. In healthy older adults, greater fitness is associated with better memory and increased mechanical integrity of the brain. In a population of older adults with mild cognitive impairment, there is a notable decrease in memory function and aerobic fitness compared to healthy controls, and this decrease is measurable in the mechanical properties of the brain using MRE.

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Keywords: Dementia, Neurofluids, Neurovascular, small vessel disease

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-β in the vessel walls. Prominent manifestations of CAA include enlarged perivascular spaces (ePVS) and lower amyloid-β concentrations in CSF, which may be the result of impaired brain clearance. CAA patients also demonstrate impaired evoked vascular reactivity. Whether vascular dysfunction is associated with impaired fluid movement in the human brain remains unclear. Here we show that BOLD-CSF coupling is reduced in CAA patients compared to elderly controls, which is a first demonstration of a cerebral small vessel disease affecting CSF motion.

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Peiying Liu^1,2, Zixuan Lin¹, Kaisha Hazel¹, George Pottanat¹, Cuimei Xu¹, Dengrong Jiang¹, Emma Lucke¹, Christopher E. Bauer³, Brian T. Gold³, Steven M. Greenberg⁴, Karl G. Helmer⁵, Kay Jann⁶, Gregory A. Jicha³, Joel Kramer⁷, Pauline Maillard⁸, Rachel Mulavelil⁹, Pavel Rodriguez⁹, Claudia L. Satizabal⁹, Sudha Seshadri⁹, Herpreet Singh⁵, Angel G. Velarde⁹, Danny J.J. Wang⁶, Rita R. Kalyani¹, Abhay Moghekar ¹, Paul B. Rosenberg¹, Sevil Yasar¹, Marilyn Albert¹, and Hanzhang Lu^1
1Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²University of Maryland School of Medicine, Baltimore, MD, United States, ³University of Kentucky, Lexington, KY, United States, ⁴Harvard Medical School, Boston, MA, United States, ⁵Massachusetts General Hospital, Boston, MA, United States, ⁶University of Southern California, Los Angeles, CA, United States, ⁷University of California, San Francisco, San Francisco, CA, United States, ⁸University of California, Davis, Sacramento, CA, United States, ⁹UT Health San Antonio, San Antonio, TX, United States

Keywords: Dementia, Blood vessels

Small vessel disease (SVD) related vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. However, there has not been a validated biomarker for the diagnosis and treatment monitoring of this condition. Recently, the US National Institute on Neurological Disorders and Stroke (NINDS), a branch of NIH, funded a MarkVCID consortium, the goal of which is to identify and validate clinical-trial-ready biomarkers for VCID. Cerebrovascular reactivity (CVR) MRI was one of the selected biomarkers that underwent multi-site testing. The present work reports the relationship between CVR and cognitive function, and examines whether the pre-specified hypothesis can be reproduced at each of the sites.

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Keywords: Alzheimer's Disease, Segmentation

Age at symptom onset distinctly affects thalamic nuclei alongside AD. While Early Onset AD showed significant anteroventral (AV) nucleus changes associated with increasing tau pathology, Late onset AD AV nucleus was associated with Aβ42 levels but no significant volume changes were found.

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Kirsten Mary Lynch¹, Arthur W Toga¹, and Jeiran Choupan^1,2
1USC Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, Los Angeles, CA, United States, ²Research, NeuroScope Inc., Scarsdale, NY, United States

Keywords: Alzheimer's Disease, Neurofluids

Disruption of perivascular and interstitial fluid transport in the brain may contribute to the accumulation of toxic metabolic deposits observed in neurodegeneration. However, the relationship between AD neuropathology and free water fluid dynamics are not well understood. Using multi-compartment diffusion models, we assessed the relationship between PET tau and Aβ uptake and free water diffusion properties. We found tau deposition was associated with reduced free water anisotropy in brain regions that undergo neurodegeneration in pre-clinical AD. These findings provide a preliminary link between AD pathology and fluid transfer that may indicate waste clearance functional alterations.

Yifan Zhang^1,2, Yue Wang^3,4, Zhaoqing Li^1,2, Shiping Li^3,4, Yi-Cheng Hsu⁵, Jiong Shi^3,4, Binbin Sui³, and Ruiliang Bai^1,2
1College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China, ²School of Medicine, Zhejiang University, Hangzhou, China, ³National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, ⁴Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, ⁵MR Collaboration, Siemens Healthcare, Shanghai, China

Keywords: Alzheimer's Disease, Alzheimer's Disease, Blood-brain barrier

Blood-brain-barrier (BBB) impairment is an important pathophysiological process in Alzheimer’s disease (AD). However, most neuroimaging methods assessing BBB function require contrast agent injection, limiting the methods’ application. Vascular-water-exchange imaging (VEXI), a version of filter-exchange imaging (FEXI), is a contrast-agent-free method assessing BBB permeability to water. We quantitatively measured BBB permeability using VEXI in normal subjects, mild cognitive impairment patients, and AD patients and found BBB breakdown occurred specifically in the hippocampus, worsening with disease progression. In addition, BBB permeability to water showed a significant correlation with cognitive impairment. Therefore, VEXI might be a potential contrast-agent-free neuroimaging method.

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Chaitali Anand¹, Lydia Le Page¹, Marina Radoul¹, and Myriam M Chaumeil^1
1UCSF, San Francisco, CA, United States

Keywords: Alzheimer's Disease, Spectroscopy, metabolism

Ketogenic diet (KD) may be used to treat cognitive dysfunction in Alzheimer’s disease (AD). In hAPPJ20 AD mice fed KD, improved spatial learning has been noted, but mechanisms driving this cognitive change remains unclear. Here we used ¹H MRS to probe the effect of KD on brain metabolism in hAPPJ20 mice fed either a control diet or KD. Increases in prefrontal creatine and Glx in KD-fed mice and increased Tau in male KD-fed mice were observed. Male KD-fed mice also demonstrated better spatial learning on the Morris water maze. Thus, KD may improve brain energetics and neurotransmission supporting cognitive function.

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Hansol Lee^1,2, Kyla Gaudet¹, Annie G. Bryant³, Rachel E. Bennett³, David H. Salat¹, Yi-Fen Yen¹, and Susie Y. Huang^1
1Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Korea, Republic of, ³Department of Neurology, Massachusetts General Hospital, Charlestown, MA, United States

Keywords: Alzheimer's Disease, Perfusion

The purpose of this study was to probe alterations in vessel size and their contributions to perfusion deficits observed in the early stages of Alzheimer’s disease (AD). AD and mild cognitive impairment (MCI) patients along with older and young adults underwent perfusion and diffusion magnetic resonance imaging (MRI). Increased vessel size was observed in conjunction with decreased cerebral blood flow in the hippocampus of individuals with AD and MCI. These results highlight potential pathologic mechanisms of abnormal vascular supply to the hippocampus in AD. Further investigations into vessel density and the relationship between cerebrovascular structure to AD pathology are warranted.

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Zhao Ruan¹, Weiyin Vivian Liu², and Haibo Xu^3
1Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China, ²GE Healthcare, MR Research China, Beijing, Beijing, China, ³Zhongnan Hospital of Wuhan University, Wuhan, China

Keywords: Dementia, Brain Connectivity, vascular cognitive impairment

The potential prevalence of vascular cognitive impairment (VCI) is high; early diagnosis and treatment is essential for disease prognosis. In this study, compared to healthy controls (HCs), there were differences of functional connectivity (FC) between the cerebellum and cerebral regions of VCI patients, mainly involving default mode network (DMN), sensorimotor network (SMN) and frontoparietal network (FPN). Furthermore, FC between multiple sub-regions in the cerebellum reduced in patients with VCI compared to HCs. These findings may expand our understanding of the neural mechanisms of VCI in the perspective of neurovascular coupling.

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Pragalv Karki¹, Matthew C Murphy¹, Petrice M Cogswell¹, Matthew L Senjem¹, Jonathan Graff-Radford², Clifford R Jack Jr¹, Richard L Ehman¹, and John Huston III^1
1Department of Radiology, Mayo Clinic, Rochester, MN, United States, ²Department of Neurology, Mayo Clinic, Rochester, MN, United States

Keywords: Dementia, Brain, Normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) is a brain disorder that is often misdiagnosed as Alzheimer’s or Parkinson’s disease due to overlapping symptoms. However, unlike such neurodegenerative diseases, NPH can be surgically treated by shunt placement with a success rate of around 80%, depending on phenotype. Therefore, correct diagnosis and categorization of NPH is important. As a step towards that goal, we demonstrate that analyzing the different morphologic phenotypes of NPH using magnetic resonance elastography can help establish unique viscoelastic signatures associated with each phenotype providing distinguishing biomarkers.

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Haroon R. Chughtai^1,2, David L. Thomas^3,4, Miguel Rosa-Grilo³, Eoin Mulroy³, Millie Beament³, Will Coath³, Lloyd Prosser³, Ian Malone³, Danny Alexander⁵, Frederik Barkhof ³, Catherine J. Mummery³, Nick C. Fox³, and Geoff J. M. Parker^1,6
1Centre for Medical Image Computing (CMIC), Medical Physics & Biomedical Engineering, UCL, London, United Kingdom, ²Advanced Research Computing (ARC) Centre, UCL, London, United Kingdom, ³Dementia Research Centre (DRC), UCL Queen Square Institute of Neurology, UCL, London, United Kingdom, ⁴Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, UCL, London, United Kingdom, ⁵Department of Computer Science, Centre for Medical Image Computing (CMIC), University College London, London, United Kingdom, ⁶Bioxydyn Limited, Manchester, United Kingdom

Keywords: Data Acquisition, Dementia

Structural brain imaging is vital in the diagnostic pathway for cognitive disorders and dementias, including the identification of Alzheimer’s disease. MRI is the recommended modality for this but is often not used due to long scan times and lower availability relative to CT. Reduced scan times are needed to enable more widespread adoption of MRI as a first-line modality for cognitive disorders. Our ultra-fast protocol enabled by Wave-CAIPI shows promise in reducing the diagnostic scan time for dementias from around 18 minutes to under 6 minutes whilst retaining clinical utility across several contrasts.

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Danni Wang¹, Miao Zhang², Yibo Zhao^3,4, Yudu Li^3,5, Wen Jin^3,4, Jialin Hu¹, Yaoyu Zhang¹, Biao Li², Jun Liu⁶, Binyin Li⁶, Zhi-Pei Liang^3,4, and Yao Li^1
1School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University of Medicine, Shanghai, China, ³Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁵National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁶Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University of Medicine, Shanghai, China

Keywords: Alzheimer's Disease, Spectroscopy

White matter (WM) damage plays an important role in AD and different mechanisms have been suggested for different brain areas from postmortem studies. Understanding the spatial patterns of pathological changes in WM is of great importance in AD diagnosis. Using a high-resolution 3D MRSI technique, we investigated the spatial patterns of neurometabolic changes in WM regions. We firstly derived neurometabolite vulnerability maps in AD, showing spatially varying patterns of NAA reduction and mIn elevation in WM regions, in distinct association with gray matter volume or Aβ deposition, respectively. The neurometabolic biomarkers showed improved prediction of cognitive decline of AD patients.

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Ana Tomash¹, Mahir Tazwar¹, Md Tahmid Yasar¹, Shengwei Zhang², Arnold M Evia², David A Bennett², Julie A Schneider², and Konstantinos Arfanakis^1,2
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, United States

Keywords: Dementia, Vessels, Alzheimer's disease, Aging, Hypertension

Brain arteriolosclerosis is one of the main pathologies of cerebral small vessel disease, is common in older adults, and is associated with lower cognitive and motor function and higher odds of dementia. This work combined in-vivo MRI and pathology in a community-cohort of older adults to investigate the independent association of brain arteriolosclerosis with diffusion abnormalities in white matter. Brain arteriolosclerosis was shown to be associated with lower FA and higher trace of the diffusion tensor that extended throughout white matter, and these associations were independent of the effects of other neuropathologies or white matter hyperintensities.

Zhihao Wang¹, Hongyuan Ding², Yin Tang³, Yao Tang^4,5, Ming Qi⁶, Weiqiang Dou⁷, Long Qian⁷, Yaxin Gao^8,9, Tong Wang¹⁰, Qian Zhong¹¹, Xi Yang¹⁰, Huifang Tian¹², Ling Zhang², and Yi Zhu^10
1School of Biological Science & Medical Engineering, Southeast University, Nanjing, China, ²Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, ³Department of Medical imaging, Jingjiang People's Hospital, Jingjiang, China, ⁴School of Rehabilitation Medicine, Nanjing Medical University, Nanjing, China, ⁵Rehabilitation Medicine Department, Geriatric Hospital of Nanjing Medical University, Nanjing, China, ⁶Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Naning, China, ⁷MR Research China, GE Healthcare, Beijing, China, ⁸Department of Rehabilitation, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China, ⁹Gusu School, Nanjing Medical University, Suzhou, China, ¹⁰Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, ¹¹Department of Rehabilitation, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China, ¹²Clinical Medicine Research Institution, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Keywords: Alzheimer's Disease, Neurodegeneration

In this study, the topology of normalized individual morphological network (IMN) has been investigated for patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and healthy controls (HCs), respectively. Significantly different topology has been revealed among SCD and MCI patients and HCs, both at global and regional level. Moreover, the alterations of the regional topological metrics, including degree centrality and nodal efficiency, at the caudate nucleus exhibited significant correlations with all clinical scales and statistically predicted the cognitive performances. Therefore, the alterations of IMN can be regarded as an effective biomarker in early detection of SCD and MCI.

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Keywords: Alzheimer's Disease, Quantitative Imaging

Morphometric and quantitative MRI metrics have rarely been used simultaneously to characterize healthy aging and Alzheimer’s disease (AD) progression. Here, cortical vertex-wise and hippocampal voxel-wise metrics were extracted to infer atrophy progression (using cortical thickness, surface area or relative Jacobians), myelin and iron contents (T1 and T2* respectively). A data-driven approach was used to parcellate the cortex and the hippocampus. A multivariate statistical technique was used to link hippocampal and cortical metrics to demographics and cognitive scores of interest. Our results suggest that AD-related neural risk is associated with neurodegeneration and microstructural changes in the cortex and hippocampus, respectively.