Gottesman Lab: New Space Activation

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications & trials

Abstract

Background: Vascular risk factors are associated with cognitive decline and dementia, especially when evaluated in middle age. Whether these same risk factors determine risk of cognitive impairment after stroke, a condition where vascular risk is generally elevated, is not clear, nor is the role of other modifiable risk factors. Furthermore, whether the mechanism of a vascular impact on cognition is solely via identifiable imaging markers of cerebrovascular disease (such as small vessel disease, silent infarcts or microbleeds) or whether there are other mechanisms by which vascular risk contributes to cognitive impairment is not well understood. Ongoing studies in the SCAN section evaluate related questions to VCID presence, etiology, and potential pathways for prevention. Findings this year: The SCAN lab was initiated in May 2021, when PI R. Gottesman came to the NINDS, and thus many findings represent an extension of work done before her arrival to the institute, as well as some new studies initiated since May 2021. In the ARIC study, which is a study of individuals from four U.S. communities who were recruited randomly from those communities in 1987-1989 and have been followed since then, through collaboration with colleagues at extramural institutions, we found that a blood-based biomarker of amyloid-beta, when measured in middle age, was associated with risk of mild cognitive impairment and dementia. In particular, higher plasma amyloid-beta 42:amyloid-beta 40 ratio was associated with a lower risk of MCI or dementia over several decades. Relationships were not as strong when late-life plasma biomarkers were considered. Also in ARIC, late-onset epilepsy, which in earlier papers we have shown is an important risk factor for cognitive decline and dementia, and is associated with vascular risk factors, is associated with an elevated risk of death, which is partially attributed to stroke and dementia. Other ongoing and submitted ARIC papers evaluate the role of other vascular and modifiable risk factors for cognitive decline and dementia, and the association between white matter hyperintensities (a marker of cerebral small vessel disease) and brain amyloid deposition (by PET, in the ARIC-PET study), the role of cardiac disease and myocardial infarction in cognitive decline (in ARIC and other cohorts), and the risk of dementia in individuals with stroke, as well as the role of stroke severity and stroke recurrence in this risk. In other work, we have evaluated racial and ethnic disparities in thrombolysis, across the U.S. (using data from the Nationwide Inpatient Sample).