Neurol Sci (2012) 33:839–846 DOI 10.1007/s10072-011-0845-4
ORIGINAL ARTICLE
Neurologic signs in relation to cognitive function in subcortical ischemic vascular dementia: a CREDOS (Clinical Research Center for Dementia of South Korea) study Seong Hye Choi • SangYun Kim • Seol-Heui Han • Duk L. Na • Doh-Kwan Kim Hae-Kwan Cheong • Jae-Hong Lee • Seong Yoon Kim • Chang Hyung Hong • So Young Moon • Jay C. Kwon • Jung Eun Kim • Jee H. Jeong • Hae Ri Na • Kyung Ryeol Cha • Sang Won Seo • Yong S. Shim • Jun-Young Lee • Kyung Won Park
•
Received: 11 December 2010 / Accepted: 28 October 2011 / Published online: 9 November 2011 Ó Springer-Verlag 2011
Abstract The objective of this study was to investigate the relationship between neurologic signs and cognitive dysfunction in subcortical ischemic vascular dementia (SIVD). 121 patients with SIVD were recruited from multiple nationwide hospitals. The patients’ neurologic signs were evaluated using the Focal Neurologic Sign Score (FNSS). The FNSS scores did not correlate with the composite neuropsychology scores and Korean Mini-Mental State Examination scores. The FNSS scores correlated with the letter fluency and Rey–Osterrieth Complex Figure (ROCF) copy scores. Using a multivariate regression analysis controlled for
age, sex, and educational level, the FNSS scores had a significant relationship with the letter fluency test scores (R2 = 0.08, b = -2.28, p = 0.02) and ROCF copy scores (R2 = 0.08, b = -0.42, p = 0.03). These findings suggest that the neurologic signs in patients with SIVD do not correlate with global cognitive functions; however, these signs do correlate with executive dysfunction in these patients.
S. H. Choi Department of Neurology, Inha University School of Medicine, Incheon, South Korea
H.-K. Cheong Department of Social and Preventive Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
S. Kim J. E. Kim Department of Neurology, Seoul National University College of Medicine, Seoul, South Korea S. Kim (&) Department of Neurology, Seoul National University Bundang Hospital, Gumi-dong 300, Bundang-gu, Seongnam 463-707, Gyeonggi-do, South Korea e-mail:
[email protected] S.-H. Han Department of Neurology, Konkuk University School of Medicine, Seoul, South Korea D. L. Na S. W. Seo Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea D.-K. Kim Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Keywords Subcortical ischemic vascular dementia Neurologic sign Executive dysfunction Cognition Small-vessel disease White matter changes
J.-H. Lee Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea S. Y. Kim Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea C. H. Hong Department of Psychiatry, Ajou University School of Medicine, Suwon, South Korea S. Y. Moon Department of Neurology, Ajou University School of Medicine, Suwon, South Korea J. C. Kwon Department of Neurology, Changwon Fatima Hospital, Changwon, South Korea
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Introduction Vascular dementia is the second most common type of dementia after Alzheimer’s disease (AD) [1, 2]. The incidence of vascular dementia is higher in Asian countries than in Western countries [1–4]. This condition can result from multiple large, complete infarcts, a single strategic infarct, multiple lacunes, widespread incomplete ischemic lesions, or a brain hemorrhage [5]. Subcortical ischemic vascular dementia (SIVD), caused by either small-vessel disease or by hypoperfusion, is one of the most common types of vascular dementia [4–6] and is clinically homogeneous compared to other types of vascular dementia. SIVD incorporates two neuropathological conditions: the lacunar state and Binswanger’s disease. The occlusion of the arteriolar lumen due to arteriolosclerosis leads to the formation of lacunes. In addition, critical stenosis and hypoperfusion of multiple medullary arterioles lead to widespread incomplete infarctions of the deep white matter, resulting in Binswanger’s disease [7]. Often, lacunes and white-matter lesions occur in the same SIVD patient. Loss of executive function and mild memory deficits were proposed as the major components of cognitive disabilities for the diagnostic criteria of SIVD [8]. The cognitive profile of vascular dementia depended on the anatomical distribution of the vascular insults. The white matter changes (WMCs) were most abundant in the frontal region, and regardless of the location in the brain where these WMCs were located, they were associated with frontal hypometabolism and executive dysfunction [9].
J. H. Jeong Department of Neurology, Ewha Womans University School of Medicine, Seoul, South Korea H. R. Na Department of Neurology, Bobath Memorial Hospital, Seongnam, South Korea K. R. Cha Department of Psychiatry, MunGyeong Jeil General Hospital, MunGyeong, South Korea Y. S. Shim Department of Neurology, School of Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Bucheon, South Korea
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Previous studies reported that subcortical vascular disease was associated with deficits in working memory and visuomotor speed and with executive dysfunction [10, 11]. The other core feature of SIVD is the presence or history of focal neurologic signs that are consistent with subcortical cerebrovascular disease [8]. However, previous reports addressing the prevalence of specific neurologic signs in SIVD are rare. In a recent study, SIVD was found to be associated with non-focal signs, such as extrapyramidal signs, and with signs of lateralization, such as hemimotor dysfunction [12]. However, lower facial weakness, which is a common focal neurologic sign in SIVD, was not assessed in the study. SIVD incorporates both cognitive and motor impairments. Motor symptoms and cognitive impairments lead to distress for patients with SIVD and for their caregivers. However, motor symptoms have received less attention in SIVD research. Although cognitive dysfunctions and focal neurologic signs are core features of SIVD, the relationship between these two features has not been studied. Whether the neurologic signs in SIVD are proportionate to the level of cognitive dysfunction is unknown. The objective of this study was to investigate the relationship between the neurologic signs and cognitive dysfunction in SIVD patients.
Methods Subjects In the present study, 121 patients with SIVD were selected from the participants of the Clinical Research Center for Dementia of South Korea (CREDOS) study. The patients included in the present study met the criteria for vascular dementia as described by the Diagnostic and Statistical Manual of Mental Disorders—fourth edition [13], had at least one focal sign identified using the Focal Neurologic Sign Score (FNSS) evaluation (described later), and had severe ischemic changes associated with small-vessel disease on T2-weighted and FLAIR images. The severe ischemic changes observed in the images were defined as periventricular WMCs with a cap or rim larger than 10 mm in maximum diameter and severe deep subcortical WMCs that were consistent with extensive or diffusely confluent WMCs C25 mm in maximum diameter. The patients who had cortical or cortico-subcortical territorial infarcts and watershed infarcts on the images were excluded.
J.-Y. Lee Department of Psychiatry, Boramae Hospital, Seoul National University, Seoul, South Korea
The CREDOS study
K. W. Park Department of Neurology, Dong-A University College of Medicine, Pusan, South Korea
The CREDOS is a multicenter cohort from 30 nationwide hospitals in South Korea that consecutively recruits subjects with subjective memory impairment, mild cognitive
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impairment, AD, or SIVD. As of 2010, the CREDOS was in its sixth year. The SIVD patients for the current study came from a cohort of patients that completed their registration with the CREDOS between September 2005 and December 2008. The participants underwent extensive neuropsychological tests, brain MRIs, and laboratory tests that included the thyroid function test (TFT), a test measuring serum levels of vitamin B12 and folate, and the venereal disease research laboratory test. Each patient had a reliable caregiver who was able to provide investigators with requested information. The exclusion criteria included an abnormal result on the TFT, a deficiency in vitamin B12 or folate, syphilis, major depressive disorder, psychosis, mental retardation, a history of encephalitis, head trauma with loss of consciousness longer than 1 h, metabolic encephalopathy, a brain tumor, a traumatic intracranial hemorrhage or a subarachnoid hemorrhage, sick-sinus syndrome, a second or third degree atrioventricular block, severe pulmonary, hepatic, or renal disease, an active gastric ulcer, uncontrolled diabetes mellitus, and uncured malignancy. The participants and their caregivers took part in two structured protocols that were devised by the CREDOS: the Clinical Evaluation Form administered by a neurologist or psychiatrist and the Caregiver Questionnaire Form administered by the caregiver under the supervision of physicians. When these protocols were completed, the investigators obtained information regarding the participants’ cognition, abnormal behaviors, activities of daily living (ADL), demographic characteristics, vascular risk factors, and other comorbidities. In addition, the investigators administered the following questionnaires or bedside tests: the Korean Mini-Mental State Examination (K-MMSE) [14], the Korean version of the Geriatric Depression Scale (GDS-K) [15], the FNSS, the Clinical Dementia Rating (CDR) scale [16], the Hachinski Ischemic Score (HIS) [17], and the Seoul-Instrumental ADL (S-IADL) [18]. The S-IADL score was determined using a 15-item questionnaire about activities that included using the telephone, shopping, meal preparation, housekeeping, mode of transportation, travelling a short distance, taking medication, handling money, grooming, using electrical equipment, finding belongings, locking a door, keeping an appointment, talking about a recent event, and hobbies. For each item, a four-point scale (0–3) was used that ranged from 3, ‘unable to do’, to 0, ‘independent activity’. The S-IADL scores ranged from 0 to 45. Higher scores were indicative of more severe functional impairment. The study protocol and informed consent form were reviewed and approved by the institutional review board in each center. Prior to participation in the study, the patients gave their written informed consent to participation in the study.
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Neurologic signs assessment Neurologic signs were rated using the FNSS. The FNSS had a range of 0–38. It consisted of the following items: limitations of eye movements (score 1), dysarthria (score 1), dysphagia (score 1), pathologic laughing (score 1) and crying (score 1), lower facial weakness (score 1), weakness (score 4, score ‘1’ for each of 4 limbs) and sensory loss in limbs (score 4, score ‘1’ for each of 4 limbs), the hyperactive deep tendon reflex (DTR) (score 8, score ‘1’ each for biceps, triceps, knee, and ankle jerks for each bilateral side), the Babinski sign (score 2, score ‘1’ for each bilateral side), the Chaddock sign (score 2, score ‘1’ for each bilateral side), rigidity of upper limbs (score 1), rigidity of lower limbs (score 1), axial rigidity (score 1), bradykinesia (score 1), hemiplegic gait (score 1), ataxic gait (score 1), stooped posture (score 1), decreased arm swing while walking (score 1), short-step gait (score 1), festinating gait (score 1), shuffling gait (score 1), and multi-step turning (score 1). Neuropsychological assessment A battery of tests that assessed a range of cognitive abilities was administered. Each patient’s attention was measured using the Forward Digit Span Test. Each patient’s verbal memory was measured using the immediate and delayed recall tests and the recognition test of the Seoul Verbal Learning Test (SVLT) using a 12-word list [19]. Each patient’s visuoconstruction was measured using the Rey– Osterrieth Complex Figure (ROCF) copy test. Each patient’s visual memory was measured using the immediate and delayed recall tests and the recognition test of the ROCF. Each patient’s language function was measured using the Short Form of the Korean version of Boston Naming Test (15 items) [20]. Each patient’s executive functions were measured using the letter fluency test, the animal fluency test, the Backward Digit Span test, and the Stroop Color-Word test. Statistical analysis To allow for a direct comparison between these different tests, we generated z scores for the neuropsychological measures. These scores were based on the means and standard deviations of each measure in the age- and education-matched control group [19]. A z score defines where a score falls in the distribution of scores for normal subjects; a z score of ?2.0 corresponds to a score that is 2 SD above the mean score. A direct comparison of the performance on these tests was possible because the z scores for all of the tests were calculated using an identical control population. The verbal memory score was estimated by
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averaging the z scores from the immediate word recall test, the delayed word recall test, and the word recognition test of the SVLT. The visual memory score was estimated by averaging the z scores of the immediate recall test, the delayed recall test, and the recognition test of the ROCF. The composite neuropsychology score was estimated by averaging the z scores of all the neuropsychological subtests. To test for a correlation with the FNSS, the results of the K-MMSE were also transferred to z scores based on the means and the standard deviations in the age- and education-matched control group [19]. The distribution of the FNSS was not normal. Therefore, the correlations between the FNSS and the clinical or neuropsychological variables were examined using Spearman correlations. The multivariate regression analyses controlling for age, gender, and education were used to test the associations of the letter fluency and ROCF copy scores with the FNSS scores. Student t tests were used to test the associations of the letter fluency and ROCF copy scores with each neurological sign. The statistical software SPSS-18 for Windows was used for data analysis. A p value of \0.05 was considered to be significant for all analyses.
Results A total of 121 patients with SIVD (45 men and 76 women) were included in the present study. The demographic and clinical characteristics for the patients are displayed in Table 1. On average, patients were mildly to moderately demented with a mean K-MMSE score of 18.2 ± 4.9. The patients had a mean FNSS score of 9.8 ± 8.1 and a mean HIS score of 6.8 ± 3.2. The patients in the present study had a mean number of lacunes of 2.4 ± 2.5. The prevalence for specific neurologic signs in the patients is shown in Fig. 1. The Chaddock sign was the neurologic sign that was observed most often (49.6%), followed by stooped posture (47.1%), decreased arm swing (47.1%),
Table 1 Baseline clinical characteristics and correlations between the Focal Neurologic Sign Score and clinical variables
Data are presented as mean ± standard deviation or as number with the percentage in a parenthesis a
A score that was estimated by averaging the z scores of all the neuropsychological subtests
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bradykinesia (46.3%), and rigidity (43.8%). The symptom that was most seldom observed was bilateral sensory dysfunction (1.7%), followed by ataxic gait (2.5%) and hemisensory dysfunction (3.3%). In an additional analysis, the majority of patients with SIVD (69.4%) exhibited at least one extrapyramidal sign (stooped posture, decreased arm swing while walking, short-step gait, festinating gait, shuffling gait, multi-step turning, rigidity, or bradykinesia), and 57.9% of the patients with SIVD exhibited at least one unilateral lateralizing sign (hemimotor dysfunction, hemisensory dysfunction, unilateral lower facial weakness, reflex asymmetry, a unilateral Babinski sign, a unilateral Chaddock sign, or hemiplegic gait). The correlations between the FNSS scores and the clinical variables are also presented in Table 1. The FNSS scores did not correlate with age, sex, educational level, or disease duration. Similarly, the FNSS scores did not correlate with the composite neuropsychology scores or the scores of the S-IADL, GDS-K, K-MMSE, and CDR-Sum of Boxes (CDR-SB). The FNSS scores were compared to selected neuropsychological measures in Table 2. Our analysis showed a significant correlation of the FNSS scores with the letter fluency scores (r = -0.20; p = 0.04) and the ROCF copy scores (r = -0.22; p = 0.02). No significant correlation was noted between the FNSS scores and the scores from all of the other cognitive measures (see Table 2). Using a multivariate regression analysis that controlled for age, sex, and educational level, the FNSS scores had a significant relationship with the letter fluency test scores (R2 = 0.08, b = -2.28, p = 0.02) and the ROCF copy scores (R2 = 0.08, b = -0.42, p = 0.03) (Table 3). We conducted additional analyses to define what specific signs were associated with poor performance on letter fluency and ROCF copy test. The subjects with rigidity, sensory loss, limitation of extraocular movement or dysphagia had lower z scores of letter fluency and ROCF copy in comparison to those without the signs (Table 4).
Clinical variables
Values
Focal Neurologic Sign Score Spearman r
P value 0.06
Age, (years)
74.6 ± 6.9
-0.17
Female
76 (62.8%)
-0.12
0.18
Education, (years)
6.5 ± 5.0
0.15
0.09
Duration of disease, (months)
34.9 ± 32.6
0.14
0.14
Seoul-instrumental activities of daily living
21.4 ± 10.9
0.10
0.29
Korean version of the Geriatric Depression Scale Korean Mini-Mental State Examination
18.9 ± 7.6 18.2 ± 4.9
0.16 0.06
0.10 0.51
Composite neuropsychology scorea
-1.9 ± 1.0
-0.12
0.18
Clinical Dementia Rating scale Sum of Boxes
6.2 ± 3.2
0.07
0.42
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Fig. 1 Prevalence of neurologic signs. Percentage of patients of the total population presenting individual neurologic signs. All neurologic signs were rated in n = 121 patients with subcortical ischemic vascular dementia. DTR deep tendon reflex
Table 2 Correlations between the Focal Neurologic Sign Score and different neuropsychological tests in subcortical ischemic vascular dementia Neuropsychological test
Focal Neurologic Sign Score Spearman r
Digit span, forwards Digit span, backwards
Table 3 Association (b coefficients, and 95% confidence interval, CI) between the neuropsychological measures and the Focal Neurologic Sign Score as the Outcome, according to the regression model adjusted for age, sex, and education Neuropsychological test
Age-, sex-, and education-adjusted model
P value b
95% CI for b
P value
0.01
0.88
Letter fluency
-2.28
-4.21*-0.35
0.02
Rey–Osterrieth Complex Figure copy
-0.42
-0.81*-0.04
0.03
0.05
0.63
Letter fluency
-0.20
0.04
Animal fluency
-0.12
0.20
Stroop, color reading
-0.10
0.32
Rey–Osterrieth Complex Figure copy
-0.22
0.02
Verbal memory scorea
-0.06
0.52
Visual memory scoreb Korean version of the Boston Naming Test (15 items)
-0.17 0.002
0.07 0.98
a A score that was estimated by averaging the z scores from the immediate word recall test, the delayed word recall test, and the word recognition test of the SVLT b
A score that was estimated by averaging the z scores of the immediate recall test, the delayed recall test, and the recognition test of the Rey–Osterrieth Complex Figure
Discussion The present study focused on the relationship between neurologic signs and cognitive functioning in patients with SIVD. We found that the neurologic signs in SIVD patients did not correlate with global cognitive performance. However, these signs correlated with executive dysfunction
in these patients. A recent study reported that extensive WMCs and multiple lacunes were associated with the neurologic signs that were observed in patients with SIVD [12]. A study on the relationship between WMCs, cortical metabolism, and cognitive function reported that WMCs were predominant in the frontal lobes and that, regardless of their regional distribution, WMCs were associated with frontal hypometabolism and executive dysfunction [9]. The neurologic signs in patients with SIVD may correlate with executive dysfunction because both features were associated with WMCs and lacunes. The FNSS scores from patients with SIVD did not correlate with global cognitive performance, as measured by the K-MMSE and the composite neuropsychology scores, and the scores of the other executive function tests except letter fluency. Several explanations exist for this poor correlation. First, the motor pathway is not the same pathway that is associated with cognition. Depending on the location of the ischemic injury, a discrepancy exists
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Table 4 The comparison of the z scores of letter fluency and Rey–Osterrieth Complex Figure (ROCF) between the subjects with a specific neurologic sign and those without it z sore of letter fluency
z score of ROCF copy
Presence of a specific neurologic sign
Presence of a specific neurologic sign
Yes
No
P
Yes
No
P
Limitation of extraocular movement
-2.5 ± 0.3
-1.5 ± 0.8
0.005
-7.6 ± 3.3
-3.4 ± 3.9
0.002
Dysarthria
-1.8 ± 0.9
-1.5 ± 0.8
0.11
-4.3 ± 3.9
-3.4 ± 4.0
0.24
Dysphagia
-1.9 ± 0.9
-1.5 ± 0.8
0.025
-5.1 ± 4.0
-3.3 ± 3.9
0.03
Pathologic laughing
-1.7 ± 0.5
-1.6 ± 0.9
0.69
-3.5 ± 3.1
-3.7 ± 4.1
0.89
Pathologic crying
-0.9 ± 0.9
-1.6 ± 0.9
0.23
-1.1 ± 1.7
-3.8 ± 4.0
0.19
Lower facial weakness
-1.1 ± 0.8
-1.7 ± 0.8
0.01
-2.0 ± 3.3
-4.0 ± 4.1
0.049
Arm weakness
-1.5 ± 1.0
-1.6 ± 0.8
0.75
-3.9 ± 3.9
-3.6 ± 4.0
0.73
Leg weakness
-1.7 ± 0.9
-1.6 ± 0.8
0.44
-4.4 ± 5.5
-3.4 ± 3.2
0.21
Sensory loss in arm
-2.4 ± 0.3
-1.6 ± 0.9
0.049
-6.9 ± 4.1
-3.5 ± 3.9
0.045
Sensory loss in leg
-2.4 ± 0.3
-1.6 ± 0.9
0.049
-6.9 ± 4.1
-3.5 ± 3.9
0.045
Increased DTR in arm
-1.7 ± 0.8
-1.5 ± 0.9
0.15
-4.5 ± 4.9
-3.1 ± 3.2
0.067
Increased DTR in leg
-1.7 ± 0.8
-1.4 ± 0.9
0.054
-4.2 ± 4.6
-3.0 ± 3.0
0.11
Babinski sign
-1.7 ± 0.9
-1.6 ± 0.8
0.54
-3.9 ± 3.7
-3.6 ± 4.2
0.67
Chaddock sign Rigidity in arm
-1.7 ± 0.9 -1.8 ± 0.8
-1.5 ± 0.8 -1.4 ± 0.9
0.32 0.028
-4.0 ± 3.6 -4.4 ± 3.7
-3.4 ± 4.3 -3.2 ± 4.1
0.35 0.10
Rigidity in leg
-1.9 ± 0.8
-1.4 ± 0.8
0.004
-4.6 ± 3.8
-3.1 ± 4.0
0.046
Axial rigidity
-1.9 ± 0.8
-1.4 ± 0.8
0.01
-4.2 ± 3.7
-3.4 ± 4.1
0.30
Bradykinesia
-1.8 ± 0.8
-1.4 ± 0.9
0.08
-4.3 ± 4.9
-3.1 ± 2.9
0.11
Hemiplegic gait
-1.6 ± 1.0
-1.6 ± 0.8
0.88
-5.0 ± 6.4
-3.4 ± 3.3
0.11
Ataxic gait
-2.5 ± 0.0
-1.6 ± 0.9
0.32
-4.8 ± 6.3
-3.7 ± 4.0
0.62
Decreased arm swing
-1.7 ± 0.9
-1.5 ± 0.8
0.43
-4.2 ± 4.9
-3.3 ± 3.0
0.22
Stooped posture
-1.8 ± 0.8
-1.4 ± 0.8
0.08
-4.1 ± 3.7
-3.3 ± 4.2
0.32
Short-step gait
-1.7 ± 0.8
-1.5 ± 0.9
0.41
-4.0 ± 3.6
-3.5 ± 4.2
0.54
Festination
-1.5 ± 0.9
-1.6 ± 0.9
0.80
-3.1 ± 3.0
-3.8 ± 4.2
0.52
Shuffling gait
-1.8 ± 0.9
-1.5 ± 0.8
0.20
-4.7 ± 4.0
-3.2 ± 3.9
0.056
Multi-step turning
-1.8 ± 0.7
-1.5 ± 0.9
0.12
-4.2 ± 3.8
-3.5 ± 4.1
0.33
Data are presented as mean ± standard deviation. DTR Deep tendon reflex
between the cognitive and motor impairments. If the number of lacunes increases or if the level of hypoperfusion progresses in brain regions that are associated mainly with cognition, a cognitive impairment may increase without an increase in neurologic signs, or vice versa. In addition, many patients with SIVD may have the pathology of AD. The aggravation of dementia in these patients might not be due to the progression of ischemia or lacunes, but it may be due to the progression of the AD pathology. Previous studies suggest that many patients with clinically diagnosed vascular dementia harbor AD pathology and suggest that Alzheimer and vascular pathologies act synergistically [21–23]. In the aforementioned previous study, the relationship between WMCs, frontal hypometabolism, and executive dysfunction was not prominent in AD patients [9]. The impact of AD pathology on cortical function might overcome the effects of concomitant cerebrovascular pathology.
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In our study, FNSS scores were inversely correlated with the ROCF copy scores. The ROCF test is commonly used to assess visuospatial skills, visuoconstruction, and executive functioning [24]. Decreased visuoconstructive ability was associated with right parietal hypoperfusion in an AD patient in a previous study [25]. However, visuoconstructive errors may be secondary to executive dysfunction. Errors on the time subscale and perseveration errors on the clock-drawing test have been correlated with executive deficits [26]. SIVD patients with mild dementia had lower scores in the clock-drawing test compared to AD patients [27]. In the ROCF copy test, the drawings from vascular dementia patients were very fragmented and contained numerous perseverations and omissions compared to AD patients [28]. Therefore, poor performance in the ROCF copy test in patients with SIVD may be associated with executive dysfunction.
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Among the many signs of the FNSS, rigidity, sensory loss, limitation of extraocular movement and dysphagia were associated with poor performance on letter fluency and ROCF copy test. Executive dysfunction in SIVD may not be associated with pyramidal tract sign, but be associated with extrapyramidal and corticobulbar tract signs. Our study showed that in addition to signs of lateralization, non-focal signs such as extrapyramidal signs are also frequently observed in patients with SIVD. This finding is in agreement with a previous study [12]. The authors of the previous study reported that extensive WMCs were associated with dysarthria, dysphagia, and extrapyramidal signs and that territorial cerebral infarcts were associated with hemisensory or hemimotor dysfunction, reflex asymmetry, and hemiplegic gait [12]. Bilateral motor weakness or bilateral sensory dysfunction was rare in the SIVD patients included in this study, but bilaterally increased DTRs were more frequently observed than reflex asymmetry. Additionally, in another previous study, the bilateral increased DTRs as well as reflex asymmetries were frequently observed in patients with SIVD [12]. One limitation of our study was that we did not directly measure gait impairment or test for visuomotor dysfunction, which has been commonly observed in patients with SIVD. Another limitation in this study was that the study design was a cross-sectional cohort study, which precludes the assessment of causality or the evolution of symptomatology. Despite these limitations, to the authors’ knowledge, this study is the first to investigate the relationship between cognitive impairment and neurologic signs in patients with SIVD. The findings of this study indicate that neurologic signs in patients with SIVD may not be correlated to global cognitive dysfunction but may be associated instead with executive dysfunction. Acknowledgment This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A102065).
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