Abstract
The natural history of Alzheimer’s Disease (AD) includes significant alterations in the human connectome, and this disconnection results in the dementia of AD. The organizing principle of our research project is the idea that the expression of cognitive dysfunction in the elderly is the result of two independent processes — the neuropathology associated with AD, and second the neuropathological changes of cerebrovascular disease. Synaptic loss, senile plaques, and neurofibrillary tangles are the functional and diagnostic hallmarks of AD, but it is the structural changes as a consequence of vascular disease that reduce brain reserve and compensation, resulting in an earlier expression of the clinical dementia syndrome. This work is being completed under the auspices of the Human Connectome Project (HCP). We have achieved an equal representation of Black individuals (vs. White individuals) and enrolled 60% Women. Each of the participants contributes demographic, behavioral and laboratory data. We acquire data relative to vascular risk, and the participants also undergo in vivo amyloid imaging, and magnetoencephalography (MEG). All of the data are publicly available under the HCP guidelines using the Connectome Coordinating Facility and the NIMH Data Archive. Locally, we use these data to address specific questions related to structure, function, AD, aging and vascular disease in multi-modality studies leveraging the differential advantages of magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), MEG, and in vivo beta amyloid imaging.
Highlights
METHODSThe natural history of Alzheimer’s Disease (AD) includes significant alterations in the human connectome, and this disconnection results in the dementia of the Alzheimer’s type (DAT)
The participants are escorted to the Center for Advanced Brain Magnetic Source Imaging7 where they are prepared for the MEG scan, and complete task training
Magnetic Resonance Imaging Structural Image Processing We briefly describe here the Human Connectome Project (HCP) Minimal Processing Pipelines that are implemented at the CCF prior to the release of the data [See Glasser, et alia (Glasser et al, 2013) for details]
Summary
METHODSThe natural history of Alzheimer’s Disease (AD) includes significant alterations in the human connectome, and this disconnection results in the dementia of the Alzheimer’s type (DAT). Data from structural and functional magnetic resonance imaging (MRI) (Dai and He, 2014; Prescott et al, 2014), as well as magnetoencephalopathy (MEG) (Lopez-Sanz et al, 2019) and electroencephalography (Maestu et al, 2019; Babiloni et al, 2020) all demonstrate significant changes in neural networks even prior to the onset of clinical dementia. While such changes are not explicit in the popular A/T/N (amyloid/tau/neurodegeneration) model of AD (Jack et al, 2016), they appear to be an early consequence of the accumulation of beta amyloid (Busche and Konnerth, 2016; Nakamura et al, 2017), and may be an early warning sign of impending neurodegeneration. All of the study data are currently being uploaded to the Connectome Coordination Facility and the NIMH National Data Archive.
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