Carotid Artery Disease and Cognitive Functional Decline

Introduction

A decline in cognitive function from ischemic, hypoperfused or hemorrhagic brain lesions has been termed “vascular cognitive impairment” (VCI). While memory dysfunction is an important correlate of classic dementias, VCI is generally associated with dysfunction in executive function and processing speed. Cognitive dysfunction after stroke is a well-recognized disability. This awareness has stimulated extensive research that has established standards of diagnosis, reporting, prevention and management of cognitive impairment after stroke. The notion that atherosclerotic carotid artery occlusive disease can lead to cognitive dysfunction was first proposed by Fisher in 1951, based on a necropsy case. He postulated that carotid stenosis can produce a dementia state, and proposed that restoration of blood supply to the brain could reverse the condition. This stimulated the first carotid reconstruction (1951) and carotid endarterectomies (CEA, 1953 and 1954) on patients with stroke and carotid artery stenosis. Subsequently, stroke was recognized as a leading cause of death in the United States with about 10%–15% of instances attributable to atheroembolization from a carotid stenosis. As a result, the focus shifted to stroke prevention, which became the primary focus of carotid revascularization.

The possibility that carotid stenosis could alter cognitive function has only recently received attention again. By 2030, 20% of the US population will be 65 years of age or older. Cognitive dysfunction is the most frequently reported disability in this age group, prevalent in ∼20%, and often progresses to falls, frailty, loss of functional independence, dementia, disability, and death. Older age and male sex, genetic factors (e.g., ApoE), silent brain infarctions, white matter hyperintensities, and microbleeds are known non-modifiable risk factors associated with cognitive decline. Although vascular risk factors such as hypertension, diabetes, dyslipidemia, cigarette smoking and obesity respond to aggressive pharmacological and lifestyle modifications, long-term compliance remains challenging due to recidivism. The possible causative relationship between carotid disease and cognitive impairment offers the potential that carotid revascularization could restore cognitive function or delay progression. This chapter reviews the current state of knowledge about the pathophysiology, severity, and course of cognitive dysfunction in patients with stenosis or occlusion of the carotid arteries.

Cognitive Versus Neurologic Function

Cognitive function is the term used to describe how a person produces and controls behavioral and mental processes such as thinking, learning, remembering, problem-solving, and consciousness. Clinical observations in brain-injured patients indicate that cognitive abilities are controlled by specific regions of the brain somewhat like motor and sensory abilities. For instance, studies of the visual sensory system show that visual stimuli are initially received in the primary visual cortex. Secondary processing for detection of direction, intensity, contrast, speed, and other combined attributes of the stimulus takes place in the surrounding higher-order visual cortex. Finally, the association cortex responds exclusively to a combination of two or more sensory inputs. Therefore, cortical systems form a hierarchy based on the functions they participate in. Contemporary conceptions propose that activation and interaction of these regions occur through dedicated or shared circuits. It is the interconnections and interactions within and between such systems that give rise to specific cognitive functions. The major difference in conceptualization between what is traditionally termed a neurologic deficit versus a cognitive deficit, is that the former is based on the loss of a localized sensory or motor function (such as movement of the left arm) whereas the latter is a loss of a system (such as ability to learn new facts). Studies have clearly shown that individuals with isolated cognitive dysfunction are at greater risk for employment problems, have difficulty with activities of daily living, may require personal assistance, and may be rendered unsafe drivers. Patients may experience problems in social situations, and the impact on family relationships is also significant. Since changes may be subtle and are not commonly sought for in a routine clinical evaluation, they may persist and progress undetected with consequent high societal and healthcare system costs.

Neurologic and cognitive deficits may occur in isolation, or occur concurrently, depending on the nature and location of the cerebral injury sustained. Evidence for the coexistence of cognitive injury in patients with neurologic injury from carotid stenosis (i.e., a stroke) is quite forthcoming. However, exclusive cognitive dysfunction in these patients have traditionally not been looked for, and have therefore not been reported in any detail until quite recently. One informative view of the extent of the problem was provided in a subset analysis of the Cardiovascular Health Study which suggested that carotid stenosis may be a risk factor for cognitive dysfunction. In this epidemiologic study, 32 patients were identified with asymptomatic left carotid stenosis ≥75%. These patients, along with the rest of the cohort, were serially tested with a modified mini-mental state examination. Based on the test scores, there was a significant decline in cognitive function in 34% of the carotid stenosis patients (12/32) over 5 years without having suffered a stroke during follow-up. A similar decline was noted when patients with stenoses ≥50% were analyzed. Such a decline was not observed in the remaining cohort of over 4000 patients. The authors did caution that the study was preliminary, the sample size was small, and findings needed substantiation due to the absence of an ideal cognitive test battery designed to assess patients with carotid stenosis.

Evaluation of Cognitive Function

While neurologic examinations aim at identifying specific sensory or motor deficits, a cognitive assessment consists of administering tests that examine a set of more-or-less independent functional domains that are controlled by brain systems. Cognitive domains are further divided into component subdomains and most cognitive tests measure one or more discrete subdomains. Therefore, more than one test is generally required to assess any particular domain completely. In addition, some tests may examine combined categories of subdomains. The major cognitive domains that are commonly tested include: attention/concentration, memory, executive function, processing speed, language/verbal skills, perception including visuospatial, and motor skills ( Box 90.1 ). Most broadly accepted cognitive tests have standardized administration procedures with appropriate normative comparison groups. Guidelines for the assessment of cognition in clinical research have been published, derived largely from medical treatment outcomes studies. However, carotid stenosis is generally a unilateral disease perturbing primarily one cerebral hemisphere, a situation quite different from the global hemispheric insult (e.g., Alzheimer’s disease) suffered by patients for whom the tests were primarily developed. Cognitive batteries addressing the unique issues relating to carotid stenosis have been developed more recently. The author’s ongoing Asymptomatic Carotid Stenosis and Cognitive Function (ACCOF) group of studies are one example of an attempt to develop and validate a cognitive test battery that is comprehensive and responsive to carotid stenosis patients, while maintaining clinical feasibility (e.g., taking approximately 30 minutes to implement).

While assessing for specific cognitive deficits requires a composite of several tests, two commonly utilized cognitive screening tests are also available. Introduced in 1975, the Mini-Mental State Exam (MMSE) offers a quick (7 to 8 minutes) assessment of orientation, word recall, language abilities, attention and calculation, and visuospatial ability. The Montreal Cognitive Assessment (MoCA), is a newer test created in 1996 that also offers tasks such as a clock-drawing test and a trail test (10–12 minutes). While the MoCA is slightly more sensitive, neither can be considered a definitive test, and both are primarily screening tools for traditional dementias (e.g., Alzheimer’s) and therefore less sensitive to VCI. They do not serve well as diagnostic or differentiating tools.

Pathophysiology of Cognitive Dysfunction in Carotid Stenosis

Vascular cognitive impairment is widely described as a progressive disease resulting from accumulated ischemic injury. Symptomatic carotid disease is primarily associated with stroke and transient ischemic attacks through atheroembolization. On occasion, patients may also be rendered neurologically symptomatic from hypoperfusion secondary to stenosis with insufficient collateral compensation, “watershed infarction”. ^, In stroke-free patients, hypoperfusion and showering of atheroemboli are two important factors hypothesized to lead to cognitive dysfunction in patients with carotid stenosis or occlusion.