This is why I would never consider a carotid endarterectomy as long as the Circle of Willis is complete.
Cognitive Dysfunction and Mortality After Carotid Endarterectomy
Kristiina Relander1,2*, Marja Hietanen1,2, Krista Nuotio2,3, Petra Ijäs2,3, Irene Tikkala1,2, Eija Saimanen4, 
Perttu J. Lindsberg2,3 and 
Lauri Soinne2,3- 1Neuropsychology, Neurocenter, Helsinki University Hospital, Helsinki, Finland
- 2Clinical Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland
- 3Neurology, Neurocenter, Helsinki University Hospital, Helsinki, Finland
- 4Department of Surgery, South Karelia Central Hospital, Lappeenranta, Finland
Background: Carotid endarterectomy (CEA) has been associated with both postoperative cognitive dysfunction (POCD) and improvement (POCI). However, the prognostic significance of postoperative cognitive changes related to CEA is largely unknown. The aim of this study was to examine the associations between postoperative cognitive changes after CEA and long-term survival.
Methods: We studied 43 patients 1 day before CEA as well as 4 days and 3 months after surgery with an extensive neuropsychological test array, and followed them for up to 14 years. POCD and POCI relative to baseline were determined with the reliable change index derived from 17 healthy controls. Associations between POCD/POCI and mortality within the patient group were studied with Cox regression analyses adjusted for confounders.
Results: POCD in any functional domain was evident in 28% of patients 4 days after surgery and in 33% of patients 3 months after surgery. POCI was shown in 23% of patients at 4 days and in 44% of patients at 3 months. POCD at 3 months was associated with higher long-term mortality (hazard ratio 5.0, 95% CI 1.8–13.9, p = 0.002) compared with patients with no cognitive decline.
Conclusions: Our findings suggest that POCD in a stable phase, 3 months after CEA predicts premature death. Evaluation of postoperative cognitive changes is essential, and POCD in a stable phase after CEA should prompt scrutiny of underlying factors and better adherence to therapies to prevent recurrences and to promote early intervention in imminent deterioration.
Introduction
Carotid endarterectomy (CEA) is an effective treatment for symptomatic (1, 2) and asymptomatic (3) high-grade carotid stenosis to prevent stroke, but findings on the cognitive consequences of CEA are strikingly mixed. CEA has been associated with both postoperative cognitive dysfunction (POCD), generally found in 10–15% of patients, and postoperative cognitive improvement (POCI) in ~10% patients 1–3 months after the operation (4–10). However, the practical and prognostic significance of postoperative cognitive changes after CEA remain essentially unexplored. POCD related to other types of surgery, such as cardiac (11, 12) and non-cardiac thoracic, abdominal or orthopedic (13) surgery, has been associated with an increased mortality rate. However, studies regarding POCD and survival after revascularization of the respective cerebral hemisphere with CEA are outstandingly scarce. An association between early cognitive dysfunction <24 h after CEA and higher mortality has been shown in patients not using statins at the time of operation but not in statin users (14). However, cognitive functioning in an early postoperative phase can be obscured by surgery-related factors, such as medication, postoperative pain and emotional stress, for which POCD is more reliably defined in a stable phase, preferably more than 30 days after operation (15). It has not yet been established whether efficient cognitive performance as a function of an essentially unbroken neural network of the cerebrum plays a role in later well-being and survival after CEA.
The aim of this study was to examine the associations between postoperative cognitive changes after CEA, assessed in both an acute and a stable postoperative phase, and long-term survival. We hypothesized that the changes in postoperative cognitive performance should have profound prognostic value, especially when examined in the stable phase, 3 months after CEA.
Materials and Methods
Setting
This prospective cohort study was carried out within the Helsinki Carotid Endarterectomy Study (HeCES) (6, 16) in the Departments of Neurology and Cardiovascular and Thoracic Surgery at the Helsinki University Hospital, Finland. The study was approved by the ethical committee of the Helsinki University Hospital and performed in accordance with the ethical standards of the Declaration of Helsinki. The participants gave their written informed consent prior to their inclusion in the study.
CEA was performed between February 20, 1997 and March 23, 2000. The patients underwent a comprehensive neuropsychological assessment 1–2 days before surgery and postoperatively 4 days after operation (median 5 days after baseline assessment, range 4–8) and ~3 months after operation (median 95 days after baseline, range 69–164). Post mortem data acquisition was approved by the local Medical Ethics Committee, the National Institute for Health and Welfare and Statistics Finland. Follow-up medical history was collected from hospital archives and electronic patient records beginning from CEA until April 30, 2012 or death. Causes of death were collected from death certificates archived at Statistics Finland.
The control group participated in neuropsychological testing but was not included in long-term follow-up. They underwent neuropsychological assessments three times at similar time intervals as the patients (second assessment median 5 days after baseline, range 4–7; third assessment median 117 days after baseline, range 89–180).
Participants
A cohort of 44 consecutive CEA patients of the HeCES study (6, 16) were enrolled in this substudy upon patient consent and availability of imaging facilities and the necessary personnel during the time frames as defined by the protocol. The participants were independent in activities of daily living, had no potential cardiogenic origin of emboli, no history of previous ipsilateral CEA or radiotherapy, and had a surgically accessible symptomatic (TIA or minor stroke, i.e., no need for inpatient rehabilitation or a deficit that would be expected to be a limiting factor in the neuropsychological examination) or asymptomatic unilateral carotid stenosis of at least 70% in digital subtraction angiography (NASCET criteria).
The level of education was scored on a three-code scale according to the Finnish education system: basic level (compulsory education requiring 6–9 years of education), middle level (vocational training, matriculation examination and/or bachelor's degree requiring 8–15 years of education), or higher level (university level master's degree or higher requiring a minimum of 16 years of education). Occupational attainment was scored using a simple three-code scale: physical or manual labor workers, skilled manual professionals, and non-manual white collar workers.
A control population was included in order to account for normal variation and practice effects in neuropsychological tests in order to define criteria for POCD/POCI. The control population consisted of 17 volunteers matched for age, gender, and education and occupation level of the patients. The control population had no medications, no signs or history of cardiovascular or neurological morbidity, no excessive alcohol intake over longer periods and no family history of neurodegenerative diseases.
Surgical Management and Postoperative Care
Patients were operated under general anesthesia with routine hemodynamic and transcranial Doppler monitoring by the same surgeon with a standard approach. Sedation, induction, muscle relaxation, and maintenance of anesthesia were carried out according to the hospital practice. Shunting was performed in three patients on the basis of stump pressure. A 1.5 Tesla magnetic resonance (MR) imaging of the brain was obtained 1 day before surgery and ~4 days and 3 to 4 months after surgery.
At discharge, all patients were deemed to have adequate preventive medication, and according to the Finnish healthcare system, they were referred to primary healthcare for the continued management and follow-up of vascular risk factors.
Neuropsychological Assessment
The test battery was selected from established neuropsychological tests and classified into seven functional domains. Learning included the Logical memory subtest of the Rivermead Behavioral Memory test, the Auditory verbal learning test (10 words, sum of trials 1 to 5) and the Rey visual learning test (15 drawings, sum of trials 1 to 5). Delayed memory included delayed recall of Logical memory, the Auditory verbal learning test and the Rey visual learning test as well as recognition of the Rey visual learning test. Working memory comprised Digit span forwards and backwards. Executive functioning included the Letter Cancellation test (time to complete), the Trail Making test, part B subtracted by part A (times to complete), the Stroop test, the Word subtest subtracted by the Color subtest (times to complete) and Verbal phonemic fluency. Motor dexterity comprised Finger tapping and the Purdue Pegboard (hand contralateral to stenosis in both tests). Processing speed included the Trail Making test, part A (time to complete) and the Stroop Color subtest (time to complete). Reasoning included the Similarities and Block Design subtests of the Wechsler Adult Intelligence Scale—revised (reasoning was not assessed at 4 days). In order to minimize learning effects, parallel memory test versions were used in repeated measurements.
Missing values were not imputed. All test scores were standardized using healthy controls' baseline performance as reference. Timed z-scores were inverted so that negative z-scores always indicated worsening of cognitive performance. Domain-wise scores were formed by averaging the standardized z-scores of each patient within each functional domain.
Risk Factor Assessment
Smoking was measured in pack years (smoking years*amount of smoked packs of cigarettes per day). Preoperative depressive symptoms were assessed with the short 13-item version of the Beck Depression Inventory (BDI) (17). Symptomatic stenosis (TIA or minor stroke), body mass index (BMI) as well as occurrence of preoperative stroke, high blood pressure, diabetes and dyslipidemia were recorded at baseline. Statin use was recorded both preoperatively (>4 weeks usage before surgery) and at follow-up. Degree of preoperative white matter hyperintensities (HI) was assessed on a four-code scale (HI-1, small and focal, <5 mm; HI-2, larger focal, 6–10 mm; HI-3, focal confluent, 11–25 mm; HI-4, diffusely confluent) and categorized into HI-1 or more.
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