Memory decline is one of the earliest symptoms of Alzheimer's disease and there is a growing awareness that vascular disease can accelerate the course of decline for this dementia. Whereas both carotid endarterectomy (CEA) and carotid stenting (CAS) are effective treatments for stroke prevention in patients with severe carotid occlusive diseases, recent studies suggest that approximately a quarter of elderly adults undergoing these procedures experience cognitive decline. Our recently funded NIH project is to study memory decline with the goal of relating cognitive changes to microembolic lesions that occur during or after carotid intervention (R01 NS070308). The ultimate goal of that R01 is to identify the aspects of the surgical procedures and patient factors that increase the risk of cognitive decline so that they can be prevented. The research from that project led to the current proposal. Using a novel neuroimaging approach, we performed volumetric analysis of microemboli that were documented on post-procedural MRIs and generated a digital map of microemboli. This map remarkably resembled the general location of hemodynamic risk zone (HRZ). We have also shown decreased white matter (WM) density in these areas vulnerable to microemboli among the patients who had post-procedural memory decline. Based on our preliminary evaluations, we believe that reduced cerebral blood flow (CBF), decreased brain WM integrity, and procedure-related microembolization are intimately related. We propose a novel concept of a single model integrating all three risk factors for procedure-related cognitive deterioration. We hypothesize that brain white matter abnormality and cerebral blood flow reduction in HRZ contribute to the frequency and cognitive effects of microemboli. In this proposal, we will add diffusion tensor imaging (DTI) to evaluate white matter integrity and arterial spin labeling (ASL) to evaluate cerebral blood flow. We will first determine the effects o white matter abnormality in HRZ on carotid interventions-associated microemboli and cognitive changes;we will also examine the effects of CBF on procedure-associated microemboli and cognitive change. Through advanced neuroimaging techniques and novel analytical tools, we hope to identify a subset of patients at risk for procedure-associated cognitive deterioration. Thi proposal reflects our continuous efforts to improve interventional outcomes. Complementary to our NIH R01, this proposal will help to better understand the underlying etiology of cognitive deterioration following carotid revascularization and will potentially help to improve cognitive outcome by individualizing patient care.

Public Health Relevance

Carotid revascularization can significantly reduce the risk of stroke, but it has been associated with cognitive decline in 25% of the patients. Neuroimaging techniques that characterize white matter integrity and regional hypoperfusion have the potential to provide sensitive brain structure indicators that may be associated with memory decline following revascularization procedures. This proposal enhances an existing R01 by adding diffusion tensor imaging and arterial spin labeling, sensitive measures for white matter integrity and cerebral blood flow. The general hypothesis is that cutting-edge MRI measures can help to predict patients at risk for procedure-associated memory decline, and therefore individualized patient care can be applied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS081416-02
Application #
8548425
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Moy, Claudia S
Project Start
2012-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$140,487
Indirect Cost
$37,543
Name
Palo Alto Institute for Research & Edu, Inc.
Department
Type
DUNS #
624218814
City
Palo Alto
State
CA
Country
United States
Zip Code
94304