Predicting risk of impending cognitive decline in asymptomatic individuals with early Alzheimer's disease: Insights from cortical diffusion MRI.
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2025-01
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Neurodegeneration associated with Alzheimer's disease (AD) can start at the microstructural level years before cognitive symptoms; yet, it has been difficult to definitively detect these early changes to plan effective treatments. Using a cortical column-based analysis of high-resolution diffusion magnetic resonance imaging data, we aim to identify early microstructural neurodegeneration in the gray matter across different cortical depths and regions. We compared four groups of participants across a spectrum of cognitive decline (n = 60): cognitively normal amyloid-negative (normal controls), cognitively normal amyloid-positive (stage-1 AD), mild cognitive impairment (MCI), and AD dementia. Our results showed progressive increases in radial diffusivity across these groups in cortical regions associated with AD, and our analysis in individual asymptomatic stage-1 AD participants was able to differentiate such diffusivity increases to predict risk of impending cognitive decline in 2 participants who had cognitive decline and MCI diagnosis at their follow-up clinical examination and 11 participants who did not.
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Overson, Devon K, Trong-Kha Truong, Jeffrey R Petrella, David J Madden, Yixin Ma, Kim G Johnson, Andy J Liu, Richard J O'Brien, et al. (2025). Predicting risk of impending cognitive decline in asymptomatic individuals with early Alzheimer's disease: Insights from cortical diffusion MRI. Imaging neuroscience (Cambridge, Mass.), 3. p. IMAG.a.1037. 10.1162/imag.a.1037 Retrieved from https://hdl.handle.net/10161/33997.
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Scholars@Duke
Trong-Kha Truong
I co-lead the MR Engineering Lab, which is part of the Brain Imaging and Analysis Center at Duke University. Our research involves the development of novel magnetic resonance imaging (MRI) coil technologies – in particular integrated parallel reception, excitation, and shimming (iPRES) and integrated radio-frequency/wireless (iRFW) coils – to enable imaging, localized B0 shimming, and/or wireless communication with a single coil, thereby improving the image quality and clinical utility of MRI applications such as functional MRI and diffusion-weighted imaging in the human brain and body. We also develop new technologies for portable low-field MRI scanners to increase MRI accessibility in non-traditional locations as well as high-resolution diffusion MRI techniques to investigate the microstructure of the human brain and to detect abnormalities in neurological disorders such as Alzheimer’s disease.
Jeffrey Robert Petrella
- Quantitating and modeling physiologic processes in normal and diseased states in the central nervous system through the use of imaging
- Application and development of advanced MR imaging technologies (e.g., diffusion, perfusion and fMRI) as well as advanced image processing and analysis techniques
- Elucidating the functional unpinnings of cognitive impairment in early stage Alzheimer's disease
- Development of functional imaging biomarkers for early diagnosis and monitoring of dementia
- Functional MRI as an aid to preoperative planning in patients with potentially resectable brain lesions
David Joseph Madden
My research focuses primarily on the cognitive neuroscience of aging: the investigation of age-related changes in perception, attention, and memory, using both behavioral measures and neuroimaging techniques, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI).
The behavioral measures have focused on reaction time, with the goal of distinguishing age-related changes in specific cognitive abilities from more general effects arising from a slowing in elementary perceptual processes. The cognitive abilities of interest include selective attention as measured in visual search tasks, semantic and episodic memory retrieval, and executive control processes.
The behavioral measures are necessary to define the cognitive abilities of interest, and the neuroimaging techniques help define the functional neuroanatomy of those abilities. The PET and fMRI measures provide information regarding neural activity during cognitive performance. DTI is a recently developed technique that images the structural integrity of white matter. The white matter tracts of the brain provide critical pathways linking the gray matter regions, and thus this work will complement the studies using PET and fMRI that focus on gray matter activation.
A current focus of the research program is the functional connectivity among regions, not only during cognitive task performance but also during rest. These latter measures, referred to as intrinsic functional connectivity, are beginning to show promise as an index of overall brain functional efficiency, which can be assessed without the implementation of a specific cognitive task. From DTI, information can be obtained regarding how anatomical connectivity constrains intrinsic functional connectivity. It will be important to determine the relative influence of white matter pathway integrity, intrinsic functional connectivity, and task-related functional connectivity, as mediators of age-related differences in behavioral measures of cognitive performance.
Ultimately, the research program can help link age-related changes in cognitive performance to changes in the structure and function of specific neural systems. The results also have implications for clinical translation, in terms of the identification of neural biomarkers for the diagnosis of neural pathology and targeting rehabilitation procedures.
Andrew John Liu
While striving to provide excellent clinical care, I also have several research interests:
1. Establish novel diagnostic biomarkers along with new therapeutic targets in Alzheimer's Disease (AD) and comorbid Cerebral Amyloid Angiopathy. I currently serve as the Associate Biomarker Core lead in the Duke-UNC Alzheimer's Disease Research Center (ADRC). I am also the site Principal Investigator (PI) of a Biogen sponsored phase 2 clinical trial, CELIA (BIIB080), that targets AD-related tau through an Anti-sense oligonucleotide (ASO) mechanism. Additionally, I am the site PI of the ALNYLAM sponsored phase 2 clinical trial. This trial knocks down the expression of APP through an ASO mechanism to potentially treat Cerebral Amyloid Angiopathy (CAA).
2. Investigate a neurodevelopmental disorder, Tuberous Sclerosis Complex (TSC), which has the potential to provide insight into the pathophysiological mechanism of AD-related tau. I have published several papers on this subject and am currently the PI of the Ann B. Bussell award that is following TSC patients longitudinally to determine if TSC is an AD-related tauopathy.
3. I am interested discovering new biomarkers to diagnose various neurodegenerative diseases. I am a co-Investigator with NCCU colleagues. We have published several new tau epitopes as potential biomarkers in diagnosing AD at earlier stages and have applied for several government funding mechanisms to continue this work.
Heather Elizabeth Whitson
Dr. Whitson is a geriatrician, memory care specialist, and clinical researcher. Her career is focused on improving care options and resilience for people with multiple chronic conditions. In particular, she has interest and expertise related to how aging biology and comorbidities impact brain health and risk for Alzheimer's disease. She is co-director of the Duke/UNC Alzheimer's Disease Research Center (Duke/UNC ADRC), which aims to transform dementia care and research in Eastern North Carolina while developing novel preventions and treatment strategies for Alzheimer's disease by identifying aging-related factors across the lifespan that drive risk, progression, or experience of dementia. The Duke/UNC ADRC conducts the Memory and Aging Study, which is tracking brain and cognitive changes in over 400 individuals at risk for dementia in later life. Dr. Whitson also co-Chairs the Alzheimer's Association's Clinical Practice Guideline panel for the use of blood-based biomarkers in the diagnosis of Alzheimer's disease. As a thought leader in a national collaborative focused on the biomedical aspects of resilience, Dr. Whitson seeks to better understand biological, psychological, and contextual factors that determine how well we "bounce back" after acute health stressors and why our resilience capacity changes with age. Dr. Whitson has contributed to work examining resilience to many types of health stressors, including surgery, dialysis, infection, vascular events, and vision loss - often focused on how these stressors affect the brain. She has led multiple studies to examine how the aging brain responds to the late-life stressor of vision loss, and she has developed a rehabilitation model to improve independence in older adults living with comorbid impairments in vision and cognition.
Allen W Song
The research in our lab is concerned with advancing structural and functional MRI methodologies (e.g. fast and high-resolution imaging techniques) for human brain imaging. We also aim to improve our understanding of functional brain signals, including spatiotemporal characterizations of the blood oxygenation level dependent contrast and alternative contrast mechanisms that are more directly linked to the neuronal activities. Additional effort is invested in applying and validating the developed methods to study human functional neuroanatomy.
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