Research

Our research examines structural and functional changes in the brain with aging and age-associated neurodegenerative disease. A primary focus of this work is to determine how the common decline in vascular health with advancing age contributes to neurodegenerative changes, cognitive attenuation and the development of Alzheimer’s disease and other dementias. We utilize structural and functional neuroimaging technology as a primary tool to measure subtle alterations in tissue integrity and physiology and how those changes relate to measures of cognitive function and systemic physiology. Through these studies, we hope to advance procedures for the clinical utilization of imaging technology in the diagnosis, characterization and tracking of neurodegenerative disease as well as towards advancing understanding of the pathological mechanisms that cause dementia.

Overview

Recent Research.

A major focus of the lab is in understanding how changes in vascular health that are typical with aging may contribute to changes in brain tissue, brain function, and thinking abilities.

Recent research in our laboratory suggests that there is a strong link between vascular and neural health and that more severe vascular changes have an important role in the development of the dementia associated with Alzheimer’s disease. For example, we have found that brain tissue changes associated with vascular disease show a strong and independent association with dementia status compared to commonly recognized markers of Alzheimer’s neurodegeneration. Additionally, brain tissue changes linked to vascular disease are more prominent in individuals that develop Alzheimer’s disease within three years suggesting an important contribution of vascular disease to the eventual development of dementia. These findings have highlighted the importance of understanding the contribution of vascular physiology to cognitive decline and the development of dementia and additionally stress the need to consider vascular therapeutics in the prevention or delay of dementia in older adults.

Ongoing Research and Future Directions.

Our ongoing work aims to better understand which aspects of vascular physiology are altered in older adults that contribute to the brain changes measured in our research. We additionally aim to understand the mechanistic dependence of these changes to the development of dementia and any potential links between vascular dysfunction and more classically recognized Alzheimer’s pathology. Finally, we aim to utilize this information for the development of vascular therapies that may be used to delay or prevent the development of dementia in older adults.

Imaging Procedures

Brain Imaging Procedures

Structural Brain Imaging

Characterizing subtle changes in brain morphometry and tissue integrity is a primary goal of our research. Our morphometry work, in collaboration with Dr. Bruce Fischl utilizes advanced MRI data acquisition and analysis procedures to create computerized models of the cerebral cortex as well as subcortical structures throughout the brain. These models allow the assessment of brain changes in individuals with neurodegenerative disease, and these results could potentially be used in the early detection of that disease in other individuals. Such early detection is a critical component of therapies that aim to halt degeneration of brain tissue prior to the point where significant damage has already occurred. In addition to morphometry studies, we utilize diffusion tensor imaging (DTI) to measure brain tissue integrity and how this is altered with disease.

Cortical reconstruction technique. Top panel: example of MR image segmentation in the coronal, axial and sagittal planes (a–c). Bottom panel: example of cortical thickness maps (d-f). Citation: Salat, D.H. et al (2004). Thinning of the Cerebral Cortex in Aging. Cerebral Cortex, 14(7), 721-730. doi: 10.1093/cercor/bhh032

Functional Brain Imaging

A secondary technique in our laboratory is the measurement of brain activity through functional magnetic resonance imaging (fMRI). These techniques allow us to measure networks of neural processing with the performance of different cognitive tasks that engage different brain regions. Understanding changes in these patterns of brain activation in patient populations can be useful towards understanding the cognitive and physiological consequences of neurodegenerative changes and can be utilized in the tracking of therapeutic procedures.

significance map using fMRI analysis (taken from FreeSurfer tutorial)

FreeSurfer

Developed by the Laboratory for Computational Neuroimaging at the Martinos Center, FreeSurfer is an open source software suite for processing and analyzing (human) brain MRI images. We use FreeSurfer to perform various analyses on a variety of measures from our brain images (ie. cortical thickness estimation, fMRI analysis, longitudinal processing, tractography and more). 

example: FreeSurfer white matter parcellation method. Citation: Salat, D.H. et al (2008). Regional white matter volume differences in nondemented aging and Alzheimer’s disease. Neuroimage, 44(4), 1247-1257. doi:10.1016/j.neuroimage.2011.07.033

Acknowledgements

Our research is generously supported by: 

Funding

NIH/NINR; Biogen Idec; Advanced Brain Monitoring

Resources

Athinoula A. Martinos Center for Biomedical Imaging