Risk factors for cerebrovascular disease, such as hypertension, obesity, and diabetes, rarely occur in isolation. The clustering of three or more vascular risk factors comprises a clinical diagnosis of cardio-metabolic syndrome (CMS). In recent years, the prevalence of CMS has risen dramatically, with recent estimates of nearly 34% of US adults meeting criteria. A diagnosis of CMS in midlife, even prior to the development of clinically significant neurologic symptoms, is associated with a substantially increased risk for vascular-related neurodegenerative conditions, including vascular cognitive impairment, dementia, as well as major neurologic events such as stroke. While there is a great deal of research examining the negative impact of individual factors, such as blood pressure, on brain tissue, there is still little knowledge of the neural mechanisms underlying CMS-related changes to neural health. The current project seeks to better understand how multiple co-occurring risk factors affect vascular and neural integrity, and how cognitive and functional status is subsequently impacted. We will identify noninvasive neuroimaging, cognitive and functional biomarkers of CMS that can be used in detecting who may be at greater risk for cognitive decline and dementia. This will be accomplished with three Aims that include 1) understanding how CMS impacts specific structural and functional brain networks, 2) understanding how an index of vascular integrity, cerebrovascular reserve (CVR), impacts structural and functional brain networks in CMS, and 3) understanding how CVR interacts with structural and functional brain integrity to affect cognitive, psychiatric, and functional status. Ultimately, this project ams to provide important translational data that can be used in clinical settings for the treatment and management of multiple vascular risk factors.

Public Health Relevance

A diagnosis of cardio-metabolic syndrome is a significant risk factor for the development of cerebrovascular disease. Understanding the complex effect that multiple vascular risk factors have on structural and functional brain integrity, and on cognitive and functional status, will provide important information that can be used in targeting medical interventions that may help prevent the development of worsening disease, vascular cognitive impairment, and dementia.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Corriveau, Roderick A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard Medical School
Schools of Medicine
United States
Zip Code
Schwarz, Nicolette F; Nordstrom, Leslie K; Pagen, Linda H G et al. (2018) Differential associations of metabolic risk factors on cortical thickness in metabolic syndrome. Neuroimage Clin 17:98-108
Wolf, Erika J; Miller, Danielle R; Logue, Mark W et al. (2017) Contributions of polygenic risk for obesity to PTSD-related metabolic syndrome and cortical thickness. Brain Behav Immun 65:328-336
Spielberg, Jeffrey M; Sadeh, Naomi; Leritz, Elizabeth C et al. (2017) Higher serum cholesterol is associated with intensified age-related neural network decoupling and cognitive decline in early- to mid-life. Hum Brain Mapp 38:3249-3261
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
Wolf, Erika J; Sadeh, Naomi; Leritz, Elizabeth C et al. (2016) Posttraumatic Stress Disorder as a Catalyst for the Association Between Metabolic Syndrome and Reduced Cortical Thickness. Biol Psychiatry 80:363-71
Foley, Jessica M; Salat, David H; Stricker, Nikki H et al. (2016) Glucose Dysregulation Interacts With APOE-?4 to Potentiate Temporoparietal Cortical Thinning. Am J Alzheimers Dis Other Demen 31:76-86
Stricker, Nikki H; Salat, David H; Kuhn, Taylor P et al. (2016) Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum. Am J Alzheimers Dis Other Demen 31:68-75