ORIGINAL ARTICLE
Association between carotid stenosis or lacunar infarction and incident dementia in patients with vascular risk factors K. Kitagawaa, K. Miwab, Y. Yagitab, S. Okazakib, M. Sakaguchib and H. Mochizukib Department of Neurology, Tokyo Women’s Medical University, Tokyo, Japan; and bDepartment of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Suita, Japan
Keywords:
carotid stenosis, dementia, lacunar infarction, vascular factor Received 14 April 2014 Accepted 16 July 2014 European Journal of Neurology 2015, 22: 187–192 doi:10.1111/ene.12553
Background and purpose: The association between vascular risk factors and dementia is of interest. Several studies have shown that cerebral small vessel disease (SVD) is associated with dementia. However, the association between cerebral large vessel disease (LVD) and dementia has not been thoroughly examined. Methods: The Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, was a prospective cohort study of cardiovascular events and dementia in which patients (n = 1106) with vascular risk factors underwent carotid ultrasound. Of these patients, 600 who had normal cognitive function were included and underwent brain magnetic resonance imaging. The presence of lacunar infarction and carotid stenosis served as markers for SVD and LVD, respectively. Results: Amongst 600 patients (mean 68 years, 57% men), 261 (44%) showed lacunar infarction and 94 (16%) showed carotid stenosis. During the followup period (median 8.0 years), 57 patients had incident dementia. Patients with carotid stenosis and lacunar infarction were significantly more likely to be diagnosed with dementia (log-rank test, P = 0.037 and P < 0.001, respectively). The association between lacunar infarction and dementia remained significant after adjusting for risk factors including stroke history, apolipoprotein E genotype and years of education (hazard ratio 2.64, 95% confidence interval 1.22–6.09). However, the presence of carotid stenosis was not associated with incident dementia after adjusting for age and sex (P = 0.477). Conclusions: This study demonstrated that carotid stenosis had little association with dementia, but lacunar infarction had a significant association. The impact of SVD on dementia could be much greater than that of LVD.
Introduction The association between vascular risk factors and dementia has attracted much attention. Several prospective studies have shown that the presence of cerebral small vessel disease (SVD) including silent lacunar infarction, white matter hyperintensity and microbleeds is associated with incident dementia [1]. In addition, cerebral large vessel disease (LVD) has been shown to be related to cognitive decline [2]. Correspondence: K. Kitagawa, Department of Neurology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan (tel.: +81-3-3353-8111 (Ext 37423); fax: +81-33341-0613; e-mail: [email protected]).
2014 EAN
However, it remains unclear whether SVD and LVD influence incident dementia in a similar way. Thus, the purpose of this study was to compare the effects of SVD and LVD on incident dementia in patients with vascular risk factors. Lacunar infarction and carotid stenosis were used as markers of SVD and LVD, respectively.
Methods The present data were obtained from the Osaka Follow-up Study for Carotid Atherosclerosis, Part 2 (OSACA2), an ongoing longitudinal study in which physicians controlled risk factors for primary and
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secondary prevention of cardiovascular disease [3]. Briefly, outpatients who visited the Department of Neurology and Stroke Center at Osaka University Hospital, were aged ≥40 years and had at least one vascular risk factor, including hypertension, diabetes, dyslipidemia, history of smoking and established arteriosclerosis, documented by a transient ischaemic attack, stroke, coronary heart disease or peripheral artery disease, were enrolled. Patients were excluded from the study if they had experienced a symptomatic vascular event during the previous 3 months. Between January 2001 and December 2009, 1106 patients who underwent baseline examinations, including a clinical assessment that included medical history, inquiry into medications, physical and neurological examination, blood sampling and carotid ultrasound, were enrolled in the OSACA2 study. Amongst them, 729 outpatients underwent brain magnetic resonance imaging (MRI), which was performed to examine lesions in cases with stroke history or suspicious neurological symptoms (e.g. headache, vertigo, dizziness, numbness, syncope or subjective memory impairment). The Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale (CDR) were used to screen suspected cases of cognitive decline. Cognitive tests were obtained 3 mm and 50% diameter reduction of the carotid artery by European Carotid Surgery Trial criteria [5]. Potential risk factors
The statistical analyses were adjusted for variables that have frequently been associated with increased risk of dementia, including age, sex, education level, body mass index (BMI), apolipoprotein E (APOE) e4 allele status (having ≥1 e4 allele) and vascular risk factors (hypertension, diabetes, dyslipidemia and smoking). Patients were categorized as having a history of cerebrovascular events if they had experienced a stroke or had undergone surgical or endovascular treatment. Incident cerebrovascular events during the follow-up were also assessed and classified as a history of stroke. Hypertension was defined as blood pressure ≥140/90 mmHg on measurements taken at least twice or being on anti-hypertensive medications. Diabetes was defined as a fasting plasma glucose level ≥7.0 mmol/l, HbA1c level ≥6.5% or being on anti-diabetic therapies. Dyslipidemia was defined as a lowdensity lipoprotein cholesterol level ≥3.6 mmol/l, total cholesterol level ≥5.7 mmol/l, triglyceride level ≥1.7 mmol/l or being on cholesterol lowering therapies. Smoking was evaluated based on past and current habits. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula for Japanese patients [6]. Diagnosis of dementia
Cognitive status was assessed prospectively by a neurologist using the MMSE and CDR [7]. Patients visited the outpatient clinic to control risk factors (e.g. hypertension and dyslipidemia) every 3 months, 6 months or 1 year for the prevention of stroke. Annual evaluations were performed by trained neurologists and included a medical history, CDR score determination and a standardized neurological examination. The final follow-up data were collected in June 2013. During the interim follow-up periods, patients with suspected cognitive decline (e.g. CDR scores ≥0.5) were examined periodically by a neurologist. Clinically significant cognitive impairment was defined as an MMSE score
Association between carotid stenosis or lacunar infarction and incident dementia in patients with vascular risk factors K. Kitagawaa, K. Miwab, Y. Yagitab, S. Okazakib, M. Sakaguchib and H. Mochizukib Department of Neurology, Tokyo Women’s Medical University, Tokyo, Japan; and bDepartment of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Suita, Japan
Keywords:
carotid stenosis, dementia, lacunar infarction, vascular factor Received 14 April 2014 Accepted 16 July 2014 European Journal of Neurology 2015, 22: 187–192 doi:10.1111/ene.12553
Background and purpose: The association between vascular risk factors and dementia is of interest. Several studies have shown that cerebral small vessel disease (SVD) is associated with dementia. However, the association between cerebral large vessel disease (LVD) and dementia has not been thoroughly examined. Methods: The Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, was a prospective cohort study of cardiovascular events and dementia in which patients (n = 1106) with vascular risk factors underwent carotid ultrasound. Of these patients, 600 who had normal cognitive function were included and underwent brain magnetic resonance imaging. The presence of lacunar infarction and carotid stenosis served as markers for SVD and LVD, respectively. Results: Amongst 600 patients (mean 68 years, 57% men), 261 (44%) showed lacunar infarction and 94 (16%) showed carotid stenosis. During the followup period (median 8.0 years), 57 patients had incident dementia. Patients with carotid stenosis and lacunar infarction were significantly more likely to be diagnosed with dementia (log-rank test, P = 0.037 and P < 0.001, respectively). The association between lacunar infarction and dementia remained significant after adjusting for risk factors including stroke history, apolipoprotein E genotype and years of education (hazard ratio 2.64, 95% confidence interval 1.22–6.09). However, the presence of carotid stenosis was not associated with incident dementia after adjusting for age and sex (P = 0.477). Conclusions: This study demonstrated that carotid stenosis had little association with dementia, but lacunar infarction had a significant association. The impact of SVD on dementia could be much greater than that of LVD.
Introduction The association between vascular risk factors and dementia has attracted much attention. Several prospective studies have shown that the presence of cerebral small vessel disease (SVD) including silent lacunar infarction, white matter hyperintensity and microbleeds is associated with incident dementia [1]. In addition, cerebral large vessel disease (LVD) has been shown to be related to cognitive decline [2]. Correspondence: K. Kitagawa, Department of Neurology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan (tel.: +81-3-3353-8111 (Ext 37423); fax: +81-33341-0613; e-mail: [email protected]).
2014 EAN
However, it remains unclear whether SVD and LVD influence incident dementia in a similar way. Thus, the purpose of this study was to compare the effects of SVD and LVD on incident dementia in patients with vascular risk factors. Lacunar infarction and carotid stenosis were used as markers of SVD and LVD, respectively.
Methods The present data were obtained from the Osaka Follow-up Study for Carotid Atherosclerosis, Part 2 (OSACA2), an ongoing longitudinal study in which physicians controlled risk factors for primary and
187
EUROPEAN JOURNAL OF NEUROLOGY
a
188
K. KITAGAWA ET AL.
secondary prevention of cardiovascular disease [3]. Briefly, outpatients who visited the Department of Neurology and Stroke Center at Osaka University Hospital, were aged ≥40 years and had at least one vascular risk factor, including hypertension, diabetes, dyslipidemia, history of smoking and established arteriosclerosis, documented by a transient ischaemic attack, stroke, coronary heart disease or peripheral artery disease, were enrolled. Patients were excluded from the study if they had experienced a symptomatic vascular event during the previous 3 months. Between January 2001 and December 2009, 1106 patients who underwent baseline examinations, including a clinical assessment that included medical history, inquiry into medications, physical and neurological examination, blood sampling and carotid ultrasound, were enrolled in the OSACA2 study. Amongst them, 729 outpatients underwent brain magnetic resonance imaging (MRI), which was performed to examine lesions in cases with stroke history or suspicious neurological symptoms (e.g. headache, vertigo, dizziness, numbness, syncope or subjective memory impairment). The Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale (CDR) were used to screen suspected cases of cognitive decline. Cognitive tests were obtained 3 mm and 50% diameter reduction of the carotid artery by European Carotid Surgery Trial criteria [5]. Potential risk factors
The statistical analyses were adjusted for variables that have frequently been associated with increased risk of dementia, including age, sex, education level, body mass index (BMI), apolipoprotein E (APOE) e4 allele status (having ≥1 e4 allele) and vascular risk factors (hypertension, diabetes, dyslipidemia and smoking). Patients were categorized as having a history of cerebrovascular events if they had experienced a stroke or had undergone surgical or endovascular treatment. Incident cerebrovascular events during the follow-up were also assessed and classified as a history of stroke. Hypertension was defined as blood pressure ≥140/90 mmHg on measurements taken at least twice or being on anti-hypertensive medications. Diabetes was defined as a fasting plasma glucose level ≥7.0 mmol/l, HbA1c level ≥6.5% or being on anti-diabetic therapies. Dyslipidemia was defined as a lowdensity lipoprotein cholesterol level ≥3.6 mmol/l, total cholesterol level ≥5.7 mmol/l, triglyceride level ≥1.7 mmol/l or being on cholesterol lowering therapies. Smoking was evaluated based on past and current habits. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula for Japanese patients [6]. Diagnosis of dementia
Cognitive status was assessed prospectively by a neurologist using the MMSE and CDR [7]. Patients visited the outpatient clinic to control risk factors (e.g. hypertension and dyslipidemia) every 3 months, 6 months or 1 year for the prevention of stroke. Annual evaluations were performed by trained neurologists and included a medical history, CDR score determination and a standardized neurological examination. The final follow-up data were collected in June 2013. During the interim follow-up periods, patients with suspected cognitive decline (e.g. CDR scores ≥0.5) were examined periodically by a neurologist. Clinically significant cognitive impairment was defined as an MMSE score
