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Elizabeth Jane Fear¹, Frida Torkelsen², Heidi A Baseler³, and Aneurin James Kennerley^4
1Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy, ²Chemistry, University of York, York, United Kingdom, ³Psychology, University of York, York, United Kingdom, ⁴Sport and Exercise Science, Institute of Science, Manchester Metropolitan University, Manchester, United Kingdom

Keywords: Neurodegeneration, Magnetization transfer, 31P

 Through combined theoretical Monte Carlo stimulation and practical ³¹P Magnetisation Transfer Magnetic Resonance Spectroscopy we quantify the effects of 670 nm photobiomodulation treatment on healthy aging brains. Mitochondrial function declines with age and many pathological processes of neurodegenerative diseases stem from this mitochondrial dysfunction when they fail to produce the necessary energy required.  Therefore, an aging population coupled with associated increases in cases of neurological conditions amplifies the need to develop safe, inexpensive treatments to restore mitochondrial function and offer neuronal protection as we grow old. Evidence shows that non-invasive transcranial red/infrared photobiomodulation (PBM) therapy can offer such neuroprotective benefits.

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Hansol Lee¹, Hong-Hsi Lee¹, Laleh Eskandarian¹, Kyla Gaudet¹, Qiyuan Tian¹, Eva A. Krijnen^2,3, Eric C. Klawiter², and Susie Y. Huang^1
1Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, ³MS Center Amsterdam, Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, Netherlands

Keywords: Neurodegeneration, Aging

We studied alterations in soma and neurite signal fractions with age based on Soma And Neurite Density imaging (SANDI) in 43 healthy adults across the lifespan using multi-shell dMRI measurements acquired on the MGH Connectome scanner. We observed decreases in soma fraction with age in all cortical lobes, especially in the frontal lobe. The neurite fraction predominantly decreased with age in the genu of corpus callous. These results suggest a regionally selective aging effect on changes in compartmental composition within the brain, potentially reflecting alterations in microstructure associated with neurodegeneration.

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Mahir Tazwar¹, Arnold M Evia², Abdur Raquib Ridwan², 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: Neurodegeneration, White Matter, LATE-NC, TDP-43, neuropathology, aging

Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is a common pathological finding in the brain of older adults, but its impact on structural network integrity remains unknown. In this work, we studied structural connectivity network abnormalities associated with LATE-NC using graph theory. Our results demonstrated that severity of LATE-NC was independently associated with weaker network integration and segregation, and increased vulnerability in a network of brain regions typically affected by LATE-NC.

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Mingxing Chen¹, Yuting Shi¹, Yuyao Zhang², and Hongjiang Wei^1
1School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²School of Information and Science and Technology, ShanghaiTech University, Shanghai, China

Keywords: Neurodegeneration, Quantitative Susceptibility mapping

        The aging process of the human brain is known to be complex, resulting in considerable structural and functional changes in the brain. In this study, a brain age prediction method based on QSM was proposed and then applied to predict the brain age of PD patients. The model achieved a high prediction accuracy with the MAE of 4.40 years and the R² of 0.91 in healthy subjects. The PADs of the PD patients were significantly higher than HC subjects. The results show that brain age prediction based on QSM can provide a new biomarker to explore iron-related brain age changes.

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Benjamin T Newman^1,2, Joshua S Danoff², Morgan E Lynch³, Stephanie N Giamberardino⁴, Simon G Gregory^4,5, Jessica J Connelly², T Jason Druzgal¹, and James P Morris^2
1Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, United States, ²Department of Psychology, University of Virginia, Charlottesville, VA, United States, ³Department of Psychology, Univeristy of Southern California, Los Angeles, CA, United States, ⁴Duke Molecular Physiology Institute, Duke University, Durham, NC, United States, ⁵Department of Neurology, Duke University, Durham, NC, United States

Keywords: Neurodegeneration, Neurodegeneration

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. This study uses the epigenetic clock GrimAge to longitudinally investigate brain cellular microstructure in axonal white matter from a healthy aging cohort. We reconstructed subject-specific axonal networks damaged by white matter hyperintensities, a visible neurological manifestation of small vessel disease. A chronological age-adjusted version of GrimAge was significantly correlated with longitudinal markers of neuronal decline. This study is the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.

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Keywords: Neurodegeneration, Aging, oxygen extraction fraction, OEF, gender differences, menopause

Regionally-resolved oxygen extraction fraction was investigated in an elderly cohort. OEF was obtained from a single 3D mGRE scan using a novel integrated model of QSM phase signal and quantitative blood oxygenation level dependent magnitude signal. Whereas age showed little influence on this metabolic parameter, a pronounced gender effect was observed. A lifestyle index reflecting physical and social activity as well as alcohol and nicotine consumption showed strong correlations with OEF. Venous blood volume fraction and tissue R2*, but not tissue QSM, also reflected lifestyle influence, showing that brain age is more than number of years.

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Keywords: Neurodegeneration, Arterial spin labelling

While mid-life cardiovascular pathology may lead to late-life cognitive decline, our understanding of the role of cerebrovascular health as an intermediate biomarker is limited. We explored the association between cardiovascular health biomarkers and cross-sectional and longitudinal cerebrovascular health assessed by ASL MRI in Insight46, a well-characterised cognitively normal population-based sample. 

We found several cross-sectional and longitudinal associations between blood pressure and CBF. These findings suggest that the effects of BP on cerebrovascular health can be imaged with ASL perfusion MRI, possibly offering opportunities to prevent or intervene before cognitive decline sets in.

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KowsalyaDevi Pavuluri¹, John Huston III¹, Richard L. Ehman¹, Armando Manduca^1,2, Prashanthi Vemuri¹, Clifford R. Jack Jr¹, Matthew L. Senjem³, and Matthew C. Murphy^1
1Department of Radiology, Mayo Clinic, Rochester, MN, United States, ²Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochetser, MN, United States, ³Department of Information Technology, Mayo Clinic, Rochester, MN, United States

Keywords: Neurodegeneration, Aging, Stiffness and Cognition

Aging is associated with neurodegeneration, cognitive function decline, and increased risk of dementia. Objective methods for the longitudinal prediction of cognitive trajectories are needed for design of comprehensive prevention strategies. We tested the hypothesis that measurements of brain mechanical properties will complement existing biomarkers in predicting future cognitive decline. Using linear mixed effect modelling, we evaluated the role of baseline medial temporal stiffness in predicting future cognitive function in participants along the Alzheimer’s disease spectrum.

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Keywords: Neurodegeneration, Aging

Memory consolidation, the ability to transform newly learned information into long-term memory, declines with age. Our previous study revealed targeted neuromodulation of spindle activities can arrest memory consolidation dysfunction in aging brains through strengthening multi-target memory representations. However, whether and how spindle activities influence memory consolidation via acting on inter-regional information integration remained unclear. Here, we demonstrate in aging animals that optogenetically-evoked spindle activities alleviate memory consolidation dysfunction through modulating brain-wide inter-regional connectivity and regional genetic expression. Our work provides an approach combining fMRI analysis and genetic expression profiling to bridge systems- and molecular-level understandings of memory consolidation.

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Kwok-Shing Chan^1,2, Michelle G. Jansen¹, Joukje Oosterman¹, David G. Norris^1,3,4, Christian F. Beckmann^1,2, and José P. Marques^1
1Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands, ²Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands, ³The Erwin L. Hahn Institute, Essen, Germany, ⁴University of Twente, Twente, Netherlands

Keywords: Neurodegeneration, Aging

The effects of ageing on quantitative MRI, including R₁, R₂* and tissue susceptibility, are investigated in subcortical grey matter using a healthy cohort. General Linear Regression analysis indicates that ageing has significant impacts on these quantitative measures: the mean R₁ has inverted U-shape appearances with time, while the mean R₂* and susceptibility are closer to linear. We further studied the spatial variation in these structures and the results show that the spatial gradient of some structures (e.g. caudate and putamen) also changes with age. Normative trajectories of these parameters in subcortical grey matter associated with ageing are also investigated.

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Yu Veronica Sui¹, Ryn Flaherty¹, Arjun V. Masurkar^2,3,4, Thomas Wisniewski^2,4,5,6, Henry Rusinek^1,5, and Mariana Lazar^1
1Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States, ²Department of Neurology, New York University Grossman School of Medicine, New York, NY, United States, ³Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY, United States, ⁴Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, United States, ⁵Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, United States, ⁶Department of Pathology, New York University Grossman School of Medicine, New York, NY, United States

Keywords: Neurodegeneration, Aging

In a large cohort of healthy participants (N=349, age range 18-90 years), we characterized intracortical myelin lifespan trajectories using two commonly used myelin proxies, magnetization transfer ratio (MTR) and T1w/T2w, combined with a surface-based image processing method. We showed that both measures exhibit an inverted-U shape trajectory for most cortical regions, with T1w/T2w values peaking later than MTR. A smoothed spline fitting of the trajectories allowed further delineation of onset decline age, a potential aging milestone. Frontal and temporal lobe regions showed consistently later peak ages than parietal and sensory motor regions across MRI metrics and curve fitting methods.

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Yixin Ma^1,2, Hansol Lee^1,2, Qiyaun Tian^1,2, Susie Y Huang^1,2, and Hong-Hsi Lee^1,2
1Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Radiology, Harvard Medical School, Boston, MA, United States

Keywords: Neurodegeneration, Microstructure

The hippocampus plays an important role in cognition and memory. Microstructural alterations can happen in specific sub-regions within the hippocampus in normal aging. Applying more advanced diffusion models and pinpointing changes in specific locations in the hippocampus, though challenging, may offer greater insight into subfield-specific neurodegeneration. Here, we applied advanced biophysical models of dMRI and correlated tissue parameters with age across the unfolded hippocampal coordinates in 43 healthy adults covering a wide age span.

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Saipavitra Murali-Manohar^1,2, Aaron T. Gudmundson^1,2, Kathleen E. Hupfeld^1,2, Helge J. Zöllner^1,2, Steve C.N. Hui^1,2, Yulu Song^1,2, Christopher W. Davies-Jenkins^1,2, Tao Gong^3,4, Guangbin Wang^3,4, Georg Oeltzschner^1,2, and Richard A.E. Edden^1,2
1The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Departments of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China, ⁴Departments of Radiology, Shandong Provincial Hospital, Shandong University, Shandong, China

Keywords: Spectroscopy, Aging, T1 relaxation times, Macromolecules, Human brain

This work investigates the age-dependence of metabolite T₁ relaxation times at 3T. T₁ relaxation times were estimated by modeling the residual metabolite amplitudes in macromolecular spectra, acquired with pre-inversion. Posterior cingulate (PCC) and centrum semiovale (CSO) spectra were acquired in 102 healthy volunteers across five decades of adult life (20 to 69 years). T₁ relaxation times of both tNAA_2.0 and tCr_3.0 significantly negatively correlated with age in CSO, and not in PCC. This has important implications for MRS studies of aging which tend to assume T₁ relaxation times are constant as a function of age.

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Keywords: White Matter, Aging

Brain functions are a property of the interaction between brain areas. While much is known about cortical structure and the structural connections in the white matter, the interaction between the cortex and white matter is underexplored. Here, we aim to investigate and characterize the relationship between white and cortical changes across the lifespan. We use the functionnectome framework to associate white matter to morphological features of the cortex. Biologically, this white matter influences (or is influenced by) these cortical changes.  

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Tyler D. Robinson¹, Yutong L. Sun¹, Paul T. H. Chang¹, and J. Jean Chen^1,2,3
1Rotman Research Institute, Baycrest, Toronto, ON, Canada, ²Medical Biophysics, University of Toronto, Toronto, ON, Canada, ³Biomedical Engineering, University of Toronto, Toronto, ON, Canada

Keywords: White Matter, Microstructure

This study compared age-related differences in white matter morphology and microstructure across ten major tracts of the human brain using diffusion data from 535 participants of the Human Connectome Project in Aging. The results are additionally assessed for agreement with retrogenesis predictions of white matter decline in normal aging. While whole-brain relationships between morphometry and white matter integrity were identified, high variability was also observed between tracts. While our data do not fully support retrogenesis models, we demonstrate patterns that may provide partial support, and highlight the need for tract-specific studies of morphological-microstructural interactions in the aging white matter.