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Qian Chen^1,2 and Bing Zhang^1,2
1Department of Radiology, Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China, ²Department of Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Keywords: Alzheimer's Disease, fMRI (resting state), subjective cognitive decline

The alterations of brain dynamics and the associations with spatial navigation in individuals with subjective cognitive decline (SCD) remain unknown. In this study, 12 states with distinct brain activity were identified in a cohort of 80 SCD and 77 normal control (NC) participants using the hidden Markov model (HMM). The SCD group showed an inability to dynamically upregulate and downregulate the state with general network activation. Significant correlations between brain dynamics and spatial navigation were observed. The combined features of spatial navigation and brain dynamics showed an area under the curve of 0.854 in distinguishing between SCD and NC.

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Charith Perera¹, Renata Cruz², Noam Shemesh², David L. Thomas^3,4,5, Jack Wells¹, and Andrada Ianus^2
1UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, United Kingdom, ²Champalimaud Foundation, Lisbon, Portugal, ³Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation,, UCL Queen Square Institute of Neurology, London, United Kingdom, ⁴Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom, ⁵Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, London, United Kingdom

Keywords: Alzheimer's Disease, Arterial spin labelling

Alzheimer’s disease (AD) is characterised by many pathophysiological changes, such as the accumulation of amyloid-β. The clearing of detrimental agents, including amyloid-β proteins, from brain tissue is linked to the function of choroid plexus (CP) or blood-cerebrospinal fluid barrier (BCSFB).This study investigates for the first time BCSFB function using non-invasive ASL-based methods in a mouse model of AD. Significantly higher values of total BCSFB-mediated water delivery in AD mice relative to controls were observed as early as 8 weeks of age, and a possible (though currently non-significant) correlation with behavioural tests was identified.

Zhihong Ke¹, Yuting Mo¹, and Yun Xu^1
1Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China, nanjing, China

Keywords: Dementia, Dementia

In this study, we used the diffusion tensor image analysis along the perivascular space (ALPS)-index to evaluate glymphatic function and highlighted the reliability of using the ALPS-index in the early recognition of cognitive impairment (CI) in cerebral small vessel disease (CSVD) patients. We reported that 1) ALPS-index was a sensitive indicator to distinguish mild CI (MCI); 2) ALPS-index was an independent influencing factor of episodic memory in CSVD patients with MCI; 3) ALPS-index mediated the relationship between white matter hyperintensities and episodic memory in CSVD patients with MCI.

Minhua Ni¹, Zeyang Li¹, Ying Yu¹, Sining Li¹, Linfeng Yan¹, and Guangbin Cui^1
1Tangdu Hospital, Xi`an, China

Keywords: Dementia, fMRI (resting state)

In this study, functional and structural changes in visual network (VN) of type 2 diabetes mellitus (T2DM) were investigated using multimodal magnetic resonance imaging. We explored degree centrality (DC), amplitude of low frequency fluctuation (ALFF), fractional anisotropy (FA), DC-FA and ALFF-FA in VN. Compared with healthy controls, deteriorated DC, ALFF and DC-FA coefficients in VN were observed in T2DM. These indicators showed positive correlations with cognitive function in T2DM, especially memory and executive function. Functional-structural decoupling may be a potential image biomarker of cognitive function change in T2DM.

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Anna Marie Chen¹, Martin Gajdošík^1,2, Rosemary Peralta¹, Helena Zheng¹, Mia Gajdošík¹, Mickael Tordjman^1,3, Julia Zabludovsky¹, Dishari Azad⁴, Ajax George¹, Henry Rusinek^1,4, Yuxin Zhang⁵, LianLian Chen⁵, Guillaume Madelin¹, Christoph Juchem^2,6, Ricardo Osorio⁴, and Ivan Kirov^1,7,8
1Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States, ²Department of Biomedical Engineering, Columbia University, New York, NY, United States, ³Department of Radiology, Cochin Hospital, Paris, France, ⁴Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, United States, ⁵Department of Biostatistics, New York University School of Global Public Health, New York, NY, United States, ⁶Department of Radiology, Columbia University, New York, NY, United States, ⁷Department of Neurology, New York University Grossman School of Medicine, New York, NY, United States, ⁸Center for Advanced Imaging Innovation and Research, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States

Keywords: Alzheimer's Disease, Gray Matter, Hippocampus

The hippocampus, a vulnerable structure in Alzheimer’s disease progression, is one of the most challenging brain structures for ¹H-MRS applications. To examine whether hippocampal metabolic dysfunction in cognitively normal elderly may contribute to disease pathology, we used a validated long-TE sLASER sequence to minimize macromolecular signal contamination and chemical shift displacement errors. We tested whether, after adjusting for age, metabolites were associated with APOE4 genotype, a risk factor for amyloid accumulation; and CSF p-tau181 and left hippocampal volume, indicators of tau burden and neurodegeneration, respectively. The main result was a statistically significant direct correlation between Glx and CSF p-tau181.

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Yuto Uchida¹, Kengo Onda¹, Jill Chotiyanonta¹, Zhipeng Hou¹, Juan Troncoso², Susumu Mori¹, and Kenichi Oishi^1
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Keywords: Alzheimer's Disease, Microstructure

Conventional neuroimaging biomarkers for the neurodegeneration of Alzheimer’s disease (AD) are not sensitive enough to detect neurodegenerative alterations in preclinical AD individuals. We aimed to examine microstructural neurodegeneration of the entorhinal-hippocampus pathway during the pathological process of AD. Our ex vivo comparative study of 11.7T MRI and histology successfully visualized microstructural neurodegeneration of the entorhinal-hippocampus pathway in preclinical AD brain tissues. In a future study, we aim to translate the findings from ex vivo 11.7T MRI and histology into in vivo MRI clinical research for preclinical AD individuals.

Arkaprava Majumdar¹, Neha Yadav¹, and Vivek Tiwari^1
1Department of Biological Sciences, Indian Institute of Science Education and Research Berhampur, Berhampur, India

Keywords: Dementia, Modelling, Brain Age

 A certain subset of the aging population maintains the cognitive abilities with minimal structural changes with aging while another subset of people transforms to mild cognitive impairment and dementia with manifold structural variations.  Since a subset maintains the cognitive abilities, brain structural volume with aging while another subset undergoes cognitive-impairment and drastic brain structure alterations, we believe that the brain age pattern is distinct from chronological age. Here, we have used a set of MRI determined brain volumetry to determine the brain age as a measure of normal and pathological aging.

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Geon-Ho Jahng¹, Sang-Tae Kim², Hyug-Gi Kim³, Yu Mi Kim², and Jee-Hyun Cho^4
1Radiology, Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of, ²Neuroscience of Lab, Seoul National University College of Medicine, Seongnam city, Korea, Republic of, ³Radiology, Kyung Hee University Hospital, Seoul, Korea, Republic of, ⁴Korea Basic Science Institute, Cheongju-si, Korea, Republic of

Keywords: Alzheimer's Disease, Molecular Imaging

The oligomeric amyloid-b (oAβ) is a reliable feature for an early diagnosis of Alzheimer's disease (AD). Therefore, the objective of this study was to demonstrate imaging of oAβ deposits using our developed DNA aptamer called ob5 conjugated with gadolinium (Gd)- DOTA as a contrast agent for early diagnosis of AD using MRI. An oAβ-specific aptamer was developed by amide bond formation and conjugated to Gd-DOTA MRI contrast agent and/or cyanine5 (cy5). We verified the performance of our new contrast agent with AD model mice using In vivo and ex vivo fluorescent imaging and animal MRI experiments.

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Bruno Hebling Vieira^1,2,3 and Nicolas Langer^1,2,3
1Methods of Plasticity Research, Department of Psychology, University of Zurich, Zürich, Switzerland, ²Neuroscience Center Zurich (ZNZ), UZH & ETHZ, Zürich, Switzerland, ³University Research Priority Program (URPP) Dynamic of Healthy Aging, University of Zurich, Zürich, Switzerland

Keywords: Alzheimer's Disease, Neurodegeneration

We predict yearly differences in MMSE and CDR-SOB using data from the ADNI cohort ranging from five years before to five years after the imaging session. We show that models that use embeddings from a deep-learning model trained to predict brain-age or models that use bilateral hippocampi, amygdalae, and accumbens perform approximately the same as models that use baseline cognitive scores as inputs. This has potential ramifications for both clinical machine learning applications and the neurobiology of cognitive decline. In future work, we will finetune the deep-learning model and substantially increase the sample size.
 

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Alfie Wearn¹, Lars Lau Raket^2,3, and Nathan Spreng^1,4,5,6
1Montreal Neurological Institute, McGill University, Montreal, QC, Canada, ²Clinical Memory Research Unit, Lund University, Lund, Sweden, ³Novo Nordisk A/S, Søborg, Denmark, ⁴McConnell Brain Imaging Centre, McGill University, Montreal, QC, Canada, ⁵Departments of Psychology and Psychiatry, McGill University, Montreal, QC, Canada, ⁶Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada

Keywords: Alzheimer's Disease, Preclinical

Microstructural brain changes caused by early Alzheimer’s disease neuropathology may cause subtle changes in MR signal that are quantifiable using texture analysis, a branch of radiomics. We used cross-sectional and longitudinal analysis techniques in the ADNI dataset to examine changes in texture across the disease continuum. We found that biomarker positive but cognitively healthy older adults had measurably different hippocampal texture than those without biomarker risk. Longitudinal modelling revealed progressive textural change with disease severity, but with high inter-subject variability. Nonetheless, hippocampal texture provided additional information to volume in predicting cognitive decline in older adults without a diagnosis of dementia.

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Nikita Seth¹, Geunwon Kim², Magdy Selim³, Ajith J Thomas⁴, Aristotelis Filippidis⁵, Yan Wen⁶, Pascal Spincemaille⁷, Yi Wang⁷, and Salil Soman^1
1Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ²Atrius Health, Boston, MA, United States, ³Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ⁴Department of Neurological Surgery, Cooper University Health Care, Cooper Medical School of Rowan University, Camden, NJ, United States, ⁵Neurosurgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ⁶GE Healthcare, New York, NY, United States, ⁷Department of Radiology, Weill Cornell Medicine, New York, NY, United States

Keywords: Alzheimer's Disease, Quantitative Susceptibility mapping, CMB, 2D GRE, mcTFI, Anti-amyloid therapy

Cerebral microbleeds/microhemorrhages (CMB) are used for risk stratification, including for the hemorrhagic complication ARIA-H of Alzheimer’s anti-amyloid therapy. For AD, risk information is based on many trials using 2DGRE technique, which is MRI field and parameter dependent. The use of techniques that better distinguish CMB mimics, like calcifications, is limited by an unclear relationship to 2D GRE CMB depiction. In this study we found the number of CMB candidate lesions between 2D GRE and mcTFI QSM obtained during the same scan session highly correlated, suggesting mcTFI could be used in the management of pathologies evaluating presence and number of CMBs.

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Akbar Alipour¹, Pinar S Ozbay², Ameen Alqadi¹, Mackenzie Langan¹, Mehmet Kurt³, Trey Hedden ⁴, Bradley N Delman¹, and Priti Balchandani^1
1Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ²Biomedical Engineering, Boğaziçi University, Istanbul, Turkey, ³Department of Mechanical Engineering, University of Washington, Seattle, WA, United States, ⁴Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Keywords: Alzheimer's Disease, Quantitative Susceptibility mapping

Detection of iron aggregations associated with beta-amyloid in Alzheimer’s disease would help to understand the related pathophysiology in these cohorts. Aggregations of iron associated beta-amyloid should increase electron density and induce notable changes in local susceptibility value. With higher susceptibility at ultra-high field strengths, induced iron susceptibility is large enough to generate contrast relative to surrounding normal tissues that can be visualized by quantitative susceptibility techniques at 7 Tesla MRI. In this study, we used 7T MRI to analyze the iron-related pathologic markers in Alzheimer patients using the quantitative susceptibility mapping technique.

Chuan-Bin Huang¹, Yong Zhang², Ke-Xue Deng¹, and Chang Liu^1
1Radiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China, ²GE Healthcare, Shanghai, China

Keywords: Alzheimer's Disease, Quantitative Susceptibility mapping

This study investigated iron content changes using Quantitative Susceptibility Mapping (QSM) technique in AD and MCI patients, as compared with normal controls, and correlated iron deposit levels with cognitive scores to assess the clinical values of QSM in the diagnosis of AD and MCI. Bilateral caudate nucleus and right putamen showed significantly increased QSM values in AD and MCI patients as compared to healthy controls. The QSM values of right caudate nucleus correlated with the MMSE scores of AD patients. These results might indicate QSM as the potential biomarker for clinical diagnosis of AD and MCI.

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Mu-Lan Jen¹, Nishant Verma^2,3, Kevin P Cheng^2,3, Robert Moskwa¹, Grant S Roberts¹, Maria Laluzerne^2,3, Jennifer Frank^2,3, Justin Williams^2,3, Wally Block¹, Kip Ludwig^2,3,4, and Kevin M Johnson^1,5
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States, ³Wisconsin Institute for Translational Neuroengineering (WITNe) – Madison, Madison, WI, United States, ⁴Neurosurgery, University of Wisconsin-Madison, Madison, WI, United States, ⁵Radiology, University of Wisconsin-Madison, Madison, WI, United States

Keywords: Alzheimer's Disease, Velocity & Flow

This study utilizes 4D-Flow imaging to evaluate hemodynamic alterations during the period of nerve stimulation and investigates cerebral blood flow changes modulated by using 4D-Flow MRI in large animal models. Preliminary results showed cerebral blood flow increases while flow pulsatility decreases with the electrical stimulation of trigeminal nerves. This effect from neuromodulation is on the contrary to the hemodynamic alterations with aging and  AD progression, which implies the potential of neuromodulation as an alternative treatment approach in repairing glymphatic system function.

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Jessica J. Chen¹, Michael L. Alosco², Huijun Liao¹, Inga K. Koerte^3,4, Martha E. Shenton³, Robert A. Stern⁵, and Alexander P. Lin^1
1Center for Clinical Spectroscopy,Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States, ²Boston University School of Medicine, Department of Neurology, Boston University Alzheimer's Disease and CTE Centers, Boston, MA, United States, ³Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States, ⁴Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany, ⁵Neurosurgery, and Anatomy & Neurobiology, Departments of Neurology, Boston University Alzheimer’s Disease and CTE Center, Boston, MA, United States

Keywords: Alzheimer's Disease, Spectroscopy, traumatic brain injury, chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is widely found in individuals exposed to repetitive head impacts (RHI) in organized contact sports, such as football. Previous findings have determined that there is a distinct deposition of phosphorylated tau (p-tau) in its neuropathology compared to other tauopathies, including Alzheimer’s disease. However, there is a lack of diagnostic criteria that examine later-life neurochemical changes due to long-term neurologic consequences to RHI. This study uses magnetic resonance spectroscopy (MRS) to compare neurochemical markers between participants with probable Alzheimer’s disease and symptomatic chronic traumatic encephalopathy in relation to healthy controls. 

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Leo Ling Cheng^1,2, Zuzanna Kobus^1,2,3, Marta Kobus^1,2,4, Li Su⁵, and David C. Christiani^5
1Department of Radiology, Massachusetts General Hospital, Boston, MA, United States, ²Harvard Medical School, Boston, MA, United States, ³Charité - Universitätsmedizin Berlin, Berlin, Germany, ⁴Department of Radiation Oncology, Charité - Universitätsmedizin Berlin, Berlin, Germany, ⁵Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States

Keywords: Alzheimer's Disease, Spectroscopy, Metabolomics

Herein, we report our preliminary data on metabolomic associations between human lung cancer (LuCa) and Alzheimer’s disease (AD) measured from serum samples using high resolution magic angle spinning (HRMAS) MRS. The current project’s objective is to establish MRS-based tissue pathology-guided serum metabolomic profiles for matched LuCa patients, with and without AD, by comparing serum profiles measured from matched healthy controls. Initial results demonstrate the feasibility of HRMAS MRS for LuCa-AD metabolomic mechanisms investigation. Our findings serve as a foundation for innovative future diagnostic and treatment studies. 

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Ayah Elsayed¹, Tracy Melzer^2,3,4, Lynette Tippett⁵, and Catherine Morgan^5,6
1Faculty of Health & Environmental Studies, Auckland University of Technology, Auckland, New Zealand, ²Department of Medicine, University of Otago, Christchurch, New Zealand, ³NZ Brain Research Institute, Christchurch, New Zealand, ⁴School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand, ⁵Department of Psychology, University of Auckland, Auckland, New Zealand, ⁶Centre for Advanced MRI, University of Auckland, Auckland, New Zealand

Keywords: Alzheimer's Disease, Velocity & Flow

Currently 50 million people suffer from Alzheimer’s disease (AD), the most common form of dementia, yet treatment options are limited. A growing focus on the contribution of cerebrovascular (CV) health presents new possible targets for treatment. We investigated novel CV imaging markers using 4D flow MRI in a total of 43 participants with mild cognitive impairment, early AD and controls. Both the MCI and AD group had significantly reduced mean blood flow in the larger vessels of the Circle of Willis. A significantly increased pulsatility index (indicative of poorer vessel compliance) was found in the AD group compared to controls. 

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Peiyu Huang¹, Carolina Canelas Valentim², Geert-Jan Biessels², Christopher Chen³, Anna Dewenter⁴, Marco Duering^4,5, Saima Hilal³, Huiberdina L Koek⁶, Anna Kopczak⁴, Bonnie Yin Ka Lam⁷, Alexander Leemans⁸, Vincent Mok⁷, Laurien Onkenhout², Hilde van den Brink², and Alberto De Luca^9
1Department of Radiology, Zheijang University School of Medicine,, Hangzhou, China, ²UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands, ³Aging and Cognition Center, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, ⁴Institute for Stroke and Dementia Research, LMU Munich, Munich, Germany, ⁵Medical Image Analysis Center, University of Basel, Basel, Switzerland, ⁶Department of Geriatric Medicine, University Medical Center Utrecht, Utrecht, Netherlands, ⁷Division Neurology, The Chinese University of Hong Kong, Hong Kong, China, ⁸Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, ⁹Division Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands

Keywords: Dementia, White Matter

Small vessel disease (SVD) is a worldwide leading cause of dementia. Damage to white matter tracts is a key mechanism through which SVD impacts cognition. In this work, we leverage a large multicenter dataset of patients with SVD to investigate which white matter tracts are strategic in SVD, that is, robustly associated with cognitive decline. Our early results show that the corpus callosum, superior longitudinal fasciculus and thalamo parietal tracts were the most associated to processing speed, verbal memory and executive function, respectively. Tract-based measures explained additional variance (2-5%) as compared to whole brain measures.

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Wen Zhang¹, Xiance Zhao², and Bing Zhang^1
1Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, ²Philips Healthcare, Shanghai, China

Keywords: Dementia, White Matter, carotid artery stenosis

Patients with carotid artery stenosis (CAS) have a high prevalence of cognitive impairment. White matter hyperintensity (WMH) is one of the most common imaging signs of chronic brain injury in the elderly. We investigated the relationship between WMH load and cognitive decline in CAS patients. Our results suggested that Fazekas score and WMH volume quantification can be a potential simple biomarker for predicting cognitive function in CAS patients.

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Yajing Zhu¹, Xin Zhang¹, and Bing Zhang^1
1Department of Radiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

Keywords: Alzheimer's Disease, Alzheimer's Disease, fMRI

Analysis of functional connectivity changes of olfactory neural circuits in  subjective cognitive decline(SCD)under specific odor stimuli using generalized physiological and psychological interactions.