Cerebrovascular contributions to brain aging and dementia. Cerebrovascular disease (CVD) contributes in a complex manner to a host of detrimental age-related conditions including cognitive decline, neurodegeneration, and the clinical syndrome of Alzheimer's disease (AD). Still, little is known about how CVD affects the brain and cognition in these conditions. The goal of this proposal is to define the cognitive and neural consequences of CVD, and how CVD-related changes alter the course of clinical decline in AD through the use of a host of novel, advanced neuroimaging procedures.
Aim 1. To identify the contribution of CVD to brain gray (GM) and white matter (WM) degeneration in older adults and in patients with AD. Hypothesis 1. Poor Cerebrovascular health contributes to GM and WM degeneration in the frontal lobe. High stroke risk at baseline predicts subsequent tissue degeneration at follow up assessment.
Aim 2. To determine how CVD associated brain changes contribute to cognitive decline. Hypothesis 2. A relation exists between CVD and cognitive decline with strong associations between stroke risk and working memory, as opposed to long term memory.
Aim 3. To understand how CVD contributes to clinical status, brain aging, and the progression to AD. Hypothesis 3. CVD is related to changes in cognition across time with most pronounced relations between stroke risk and reduced working, as opposed to long term, memory abilities. CVD related WM degeneration is a risk for the development of dementia. CVD risk will be characterized using the Framingham Stroke Risk profile which integrates clinical and quantitative physiological data. We will model the association between CVD measures and MRI measures of with a focus on how stroke risk predicts subsequent neural degeneration and clinical decline. Measures of CVD will be related to change in cognitive abilities and imaging measures across testing sessions separated by two and four years to determine whether CVD or associated brain changes affect the rate of the conversion from mild cognitive impairment to dementia. Knowledge from the proposed studies would be useful in the differential therapeutic intervention of AD and CVD related brain degeneration.

National Institute of Health (NIH)
National Institute of Nursing Research (NINR)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Tully, Lois
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Chad, Jordan A; Pasternak, Ofer; Salat, David H et al. (2018) Re-examining age-related differences in white matter microstructure with free-water corrected diffusion tensor imaging. Neurobiol Aging 71:161-170
Sitnikova, Tatiana A; Hughes, Jeremy W; Ahlfors, Seppo P et al. (2018) Short timescale abnormalities in the states of spontaneous synchrony in the functional neural networks in Alzheimer's disease. Neuroimage Clin 20:128-152
Rosas, H D; Wilkens, P; Salat, D H et al. (2018) Complex spatial and temporally defined myelin and axonal degeneration in Huntington disease. Neuroimage Clin 20:236-242
Belathur Suresh, Mahanand; Fischl, Bruce; Salat, David H et al. (2018) Factors influencing accuracy of cortical thickness in the diagnosis of Alzheimer's disease. Hum Brain Mapp 39:1500-1515
Lindemer, Emily R; Greve, Douglas N; Fischl, Bruce R et al. (2017) Regional staging of white matter signal abnormalities in aging and Alzheimer's disease. Neuroimage Clin 14:156-165
Coutinho, Artur Martins; Coutu, Jean-Philippe; Lindemer, Emily Rose et al. (2017) Differential associations between systemic markers of disease and cortical thickness in healthy middle-aged and older adults. Neuroimage 146:19-27
Fortenbaugh, Francesca C; Corbo, Vincent; Poole, Victoria et al. (2017) Interpersonal early-life trauma alters amygdala connectivity and sustained attention performance. Brain Behav 7:e00684
Coutu, Jean-Philippe; Lindemer, Emily R; Konukoglu, Ender et al. (2017) Two distinct classes of degenerative change are independently linked to clinical progression in mild cognitive impairment. Neurobiol Aging 54:1-9
Lindemer, Emily R; Greve, Douglas N; Fischl, Bruce et al. (2017) Differential Regional Distribution of Juxtacortical White Matter Signal Abnormalities in Aging and Alzheimer's Disease. J Alzheimers Dis 57:293-303
Leritz, Elizabeth C; McGlinchey, Regina E; Salat, David H et al. (2016) Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory. Metab Brain Dis 31:465-73

Showing the most recent 10 out of 51 publications