Acta Neurochir (2009) 151:1593–1600 DOI 10.1007/s00701-009-0420-4
CLINICAL ARTICLE
Changes in cognitive function during the 1-year period following endarterectomy and stenting of patients with high-grade carotid artery stenosis Akiko Takaiwa & Nakamasa Hayashi & Naoya Kuwayama & Naoki Akioka & Michiya Kubo & Shunro Endo
Received: 26 March 2009 / Accepted: 18 May 2009 / Published online: 16 June 2009 # Springer-Verlag 2009
Abstract Background In patients with severe carotid artery stenosis, cognitive decline and changes in cognitive function before to after treatment have been noted, though the true effects of treatment in such patients remain unclear. A convenient and repeatable neuropsychological test battery is needed for such patients. Methods In 26 patients with severe carotid artery stenosis treated by carotid endarterectomy (CEA) and stenting (CAS), cognitive function was examined before and 1 week, 3 months, 6 months, and 1 year after treatment. RBANS and MMSE were selected as a test battery, and changes in test scores and long-term results of revascularization were evaluated. Results RBANS was useful and suitable for neuropsychological testing in such patients, and yielded the following results: (1) Patients before treatment had, on average, RBANS scores rated low average, with mild but relatively diffuse cognitive impairment; (2) RBANS scores were increased significantly at 3 months after CEA and CAS, and cognitive improvement was maintained over 1 year; and (3) scores were decreased temporarily at 1 week after CEA, but not after CAS. Conclusions Patients with severe carotid artery stenosis exhibited mild decline in cognitive function, which was improved after CEA and CAS. RBANS is a suitable test battery for this type of patient. A. Takaiwa : N. Hayashi (*) : N. Kuwayama : N. Akioka : M. Kubo : S. Endo Department of Neurosugery, Faculty of Medicine, University of Toyama, 2630 Sugitani Toyama, Toyama, 930-0194, Japan e-mail:
[email protected]
Keywords Cognitive function . Carotid artery stenosis . Carotid endarterectomy . Carotid artery stenting . Change over time
Introduction High-grade carotid artery stenosis is known to be a major risk factor for ischemic cerebral stroke, and the usefulness of prophylactic carotid endarterectomy (CEA) and carotid stenting (CAS) for the prevention of stroke has been evaluated in many large RCT studies. In patients with this condition, progressive cognitive decline and changes before to after treatment CEA and/or CAS have been noted [5, 7, 21, 24]. There are increasing clinical findings that surgical repair of carotid stenosis may improve cognitive function, though some other reports have noted cognitive decline due to surgical procedures. Additional studies are needed to confirm the effects of carotid stenosis and surgical repair on cognition. The goal of this study was to prospectively measure objective cognitive performance during the 1-year period following CEA and CAS in patients with symptomatic / asymptomatic high-grade carotid artery stenosis. We also examined whether the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is suitable for measurement of cognitive function in such patients.
Materials and methods This prospective study was performed under the approval of the Ethics Committee of the University of Toyama. Candidates were patients who were referred to the
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neurosurgical service of Toyama University Hospital for surgical treatment of unilateral carotid artery stenosis, between April 2004 and December 2006. The patients were screened initially by CT angiography or carotid echography, and measurements of carotid stenosis and the determination of whether to perform CEA or CAS was made by conventional angiography. The degree of carotid artery stenosis was determined using NASCET criteria. Inclusion criteria included evidence of unilateral carotid stenosis of more than 70% in symptomatic patients who had a history of TIA and/or minor stroke, and more than 80% in asymptomatic patients. Exclusion criteria included evidence of other significant stenosis (>50%) in the intracranial major arteries, previous major stroke and brain damage, history of cerebral surgery, findings of infarction on MRI or CT, and uncontrolled or malignant general complications. All patients had good levels of activities of daily living and lacked signs of neurological disorders including aphasia, apraxia, agnosia, and dementia. The neurologist, neurosurgeon, and neuroendovascular physician on our stroke care team reviewed patient data and decided whether to perform CEA or CAS. Basically, the first choice of treatment was CEA, while CAS was considered for patients at high risk with performance of CEA, according to the AHA/ASA guidelines and SAPPHIRE trial. CEA was performed under general anesthesia and in the usual fashion. An intraluminal shunt during CEA was not used in any of patients in the present study. We used brainprotective drugs during carotid occlusion, and primary closure without patching was performed. In CAS, angioplasty with PRECISE stent placement under distal protection with balloon technique was performed. All patients were treated with aspirin and/or clopidogrel (Plavix) or cilostazol before and after CEA/CAS. MRI was performed routinely at baseline and within 2 days after procedures to check for ischemic complications. Postoperative carotid artery lesions were followed by echography and/or MRA. An objective measure of cognitive performance was obtained with the Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS was developed to identify and characterize cognitive decline in the older adult, and is composed of two test batteries, forms A and B, which are parallel forms and can be used to avoid effects of learning. In each test, total score and scores for the five sections or domains of immediate memory (list learning, story memory), visuospatial/constructional (figure copy, line orientation), language (picture naming, semantic fluency), attention (digit span, coding), and delayed memory (list recall, list recognition, story recall, figure recall) were recorded. Scores can be normalized for age, sex, ethnicity, and level of education with a score of 100 and a standard deviation of 15 for the index group. The classification of RBANS index
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scores includes seven grades: very superior (index score: 130 or above, theoretical percent: 2.2%), superior (120– 129, 6.7%), high average (110–119, 16.1%), average (90– 109, 50%), low average (80–89, 16.1%), borderline (70–79, 6.7%), and extremely low (69 and below, 2.2%). The MiniMental State Examination (MMSE) was performed for comparison. Neuropsychological test scores were obtained and evaluated at baseline and 1 week, 3 months, 6 months, and 1 year after surgical procedures. Each RBANS and MMSE was performed by one experienced neuropsychologist. Statistical analysis Demographic data Age and educational background variables were examined using the Mann-Whitney U-test. Differences in sex, handedness, symptoms, side of stenosis, and side treated between CAE and CAS were examined by the Chi-square test. Effects of revascularization on cognitive function Cognitive function at baseline was examined using the Mann-Whitney U-test. Effects of revascularization on cognitive function data were examined by group-rate analysis and event-rate analysis. (1) Group-rate analysis: Effects of treatment and elapse of time were examined using a 2 (the first factor: effect of treatment type: CEA versus CAS) x 5 (the second factor: effect of elapse of time: pretreatment and after 1 week, 3 months, 6 months, and 1 year) two-way repeated-measures ANOVA. Post-hoc comparisons were performed using the Bonferroni test. The significance level was 5%. 2) Event-rate analysis: In this analysis, 95% confidence intervals for each RBANS index corresponding to each age group were used. Changes in each patient were calculated from differences in score before to after treatment. Values exceeding the confidence interval were presumed to indicate cognitive improvement or decline after treatment. Rates of change in the CEA and CAS groups after 1 week, 3 months, 6 months, and 1 year were calculated as percentages.
Results Clinical characteristics In this study, 26 patients were enrolled and written consent was obtained from each. All CEA and CAS procedures
Changes in cognitive function during the one-year period following endarterectomy and stenting of patients with high-grade carotid Table 1 Clinical characteristics
Group
Age (years) Length of education (years) Gender Male Female Dominant hand Right Left Symptomatic Asymptomatic Symptomatic Side of stenosis & side of treatment n=number ns: non-significant
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CAS (n=15)
p-value
68.0±8.9 10.8±3.0
71.6±6.9 9.7±2.5
ns ns ns
9 2
11 4 ns
11 0
14 1
6 5
6 9
9 2
6 9
ns
p=0.03
Right Left
were performed without unusual events. All RBANS and MMSE tests were completed within 40 min. Eleven of the 26 patients, including nine males and two females, were treated by CEA (CEA group). Their mean age was 68.0±8.9 (range: 52–82) years, with a mean length of education of 10.8±3.0 (range: 8–16) years. The right hand was dominant for all of these patients. The clinical breakdown was as follows: six patients were asymptomatic and five symptomatic, while nine lesions and corresponding sides of treatment were on the right, and two were on the left. The other 15 patients, including 11 males and four females, were treated with CAS (CAS group). Their mean age was 71.6±6.9 (range: 58–80) years, with a mean length of education of 9.7±2.5 (range: 8–16) years. For 14 patients the right hand was dominant, while for one patient the left hand was. The clinical breakdown was as follows: six patients were asymptomatic and nine symptomatic, while six lesions and corresponding sides of treatment were on the right and nine were on the left. The CEA and CAS groups differed significantly with respect to none of age, educational background, gender, handedness, and symptomatic status, but did differ significantly with respect to lesions and treatment side (Table 1).
CEA (n=11)
level”, three (11.5%) as “borderline level”, and two (7.7%) as “extremely low level”. During the 1-year period following treatment, scores steadily increased after CEA and CAS, and mean total score on RBANS recovered to 102±14.1 (range: index Index score 130
A: CEA group
120
case 1 case 2 case 3 case 4 case 5 case 6 case 7 case 8 case 9 case 10 case 11
110 100 90 80 70 60 pretreatment Index score 130
1 week
3 months
6 months
1 year
B: CAS group case 12 case 13 case 14 case 15 case 16 case 17 case 18 case 19 case 20 case 21 case 22 case 23 case 24 case 25 case 26
120 110 100
Neuropsychological test scores before and after CEA/CAS For the 26 patients, mean total scores of RBANS and MMSE before treatment were 88.6±13.7 (range: index score 62–118) and 27.8±1.4 (range: 25–30 point), respectively. As classified using the index score for RBANS, two patients (7.7%) were classified as “high average level”, nine (34.6%) as “average level”, ten (38.5%) as “low average
90 80 70 60
pretreatment 1 week
3 months
6 months
1 year
Fig. 1 Changes of RBANS total score with each patients in 1-year period. a CEA group patients. b CAS group patients
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score 73–124) and that on MMSE to 29.0±0.7 (range: 27– 30 points). Classification of RBANS total scale changed to “superior level” in three of 26 patients (11.5%), “ high average level” in eight (30.8%), “average level” in 12 (46.2%), “low average level” in two (7.7%), and “borderline level” in one (3.8%). Figure 1 showed changes of RBANS total score with each patients in one-year period Results of group-rate analysis of RBANS and MMSE and of event-rate analysis of RBANS are shown in Tables 2 and 3. # Group-rate analysis (Table 2) In the case of RBANS, two-way ANOVA for interaction (elapse of time x treatment type) was found to be significant for scores for immediate memory, language, and total scale. Regarding the first factor, treatment type (CEA versus
CAS), significant difference was found for no domain or total score. On the other hand, the second factor, elapse of time (pretreatment and after 1 week, 3 months, 6 months, and 1 year) was found to be significant in each of the five domains and for total score. On post-hoc comparisons, CEA and CAS exhibited different patterns of change in score (Fig. 2). In the CEA group, significant decreases in scores were revealed in the domain of visuospatial/constructional, language, and total scale at 1 week versus pretreatment. However, scores for immediate memory, attention, delayed memory, and total score were improved significantly at three months after CEA, and the score for visuospatial/constructional was also improved at 1 year after treatment. In the CAS group, test scores steadily increased after treatment, and no temporary decrease in scores was observed after 1 week as in the case of CEA. Scores for
Table 2 Cognitive performance Tests
Pretreatment
MMSE CEA 28.0±1.5 CAS 27.7±1.3 RBANS Immediate memory CEA 93.4±12.5 CAS 86.3±11.0 Visuospatial/constructional CEA 98.6±18.8 CAS 100.7±16.4 Language CEA 93.5±12.4 CAS 88.5±14.4 Attention CEA 85.1±19.3 CAS 83.5±12.1 Delayed memory CEA 94.7±18.9 CAS 91.0±14.1 Total Score CEA 91.4±17.0 CAS 86.5(SD10.8)
1week
3months
6months
1year
27.8±1.9 28.5±1.6
28.5±1.4 28.9±0.8
28.9±0.7 29.8±1.0
29.2±0.6 28.9±0.8
90.5±9.0 94.7±12.1
106.8±15.3 100.3±10.8
104.0±16.3 106.2±13.5
104.8±14.3 103.5±13.8
90.4±16.6 103.2±14.0
102.6±16.2 105.1±13.7
101.8±13.8 105.5±12.8
107.9±13.8 107.7±9.9
85.1±11.4 92.6±12.3
94.8±7.1 94.7±8.6
92.4±7.1 98.4±8.7
94.5±6.9 97.5±9.0
86.3±18.3 86.0±14.9
93.9±17.9 92.8±10.4
94.5±18.8 92.5±15.4
98.4±17.9 92.5±14.3
93.3±14.8 101.6±15.2
105.5±12.3 102.5±14.4
108.0±10.9 105.5±17.5
109.5±13.5 106.4±13.1
85.5±13.0 93.9±11.5
101.4±15.6 98.0±8.8
100.0±14.1 102.0±12.6
104.5±15.4 101.7±13.5
MMSE: Mini Mental State Examination RBANS: Repeatable Battery for the Assessment of Neuropsychological Status CEA: Carotid Endarterectomy CAS: Carotid Artery Stenting Factor 1: method of treatment (CEA versus CAS) Factor 2: elapse of time (pretreatment and after one week, three months, six months, and one year) Interaction: treatment type x elapse of time
Factor1
Factor2
Interaction
0.76
