- Email: [email protected]
Vascular characteristics of patients with dementia
Journal of the Neurological Sciences 283 (2009) 41–43
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Vascular characteristics of patients with dementia☆ Sandra Morović, Miljenka-Jelena Jurašić, Irena Martinić Popović, Vesna Šerić, Marijana Lisak, Vida Demarin ⁎ University Department of Neurology, Sestre Milosrdnice University Hospital, Vinogradska 29, Zagreb, Croatia
a r t i c l e
i n f o
Available online 16 April 2009 Keywords: Dementia-vascular Alzheimer disease Arterial stiffness Vascular ultrasound
a b s t r a c t Arterial beta stiffness index is a potential risk factor for increased stroke occurrence. Vascular component appears to be significant in both Alzheimer's disease (AD) and vascular dementia (VAD). We aimed to further explore vascular characteristics of patients with both types of cognitive decline using non-invasive neurosonological methods. There were 38 patients; 16 diagnosed with AD and 22 with VAD. Vascular risk factors were assessed and ultrasound measurements on common carotid artery (CCA) were performed using Aloka ProSound ALPHA 10 with 13 MHz linear probe. Among AD patients there were 5 with arterial hypertension (AH), 3 with atrial fibrillation (AF), 2 with diabetes mellitus (DM), 6 with hyper lipidemia and 1 smoker. Nineteen VAD patients had AH, 6 had AF, 12 had hyper lipidemia and one was diabetic. We found no statistically significant differences between groups regarding average body mass index (BMI), blood pressure, pulse pressure, intima–media thickness (IMT), CCA diameter or arterial beta stiffness indices. However, the trend of BMI increase, slight blood and pulse pressure decrease, CCA diameter increase and beta stiffness index increase was noted in VAD patients. Even though there was no significant difference found among two explored subgroups of patients with dementia, there was a tendency of greater systolic and diastolic diameters noted in VAD as well as greater stiffness, especially when measured in the right CCA. This indicates that VAD patients may have more prominent vascular changes that may help differentiate the type of dementia and further monitor these individuals. Further studies on a larger number of patients are needed support this evidence. © 2009 Published by Elsevier B.V.
1. Introduction Impaired cognition sometimes accompanies ageing. As populations grow older, so does the increase in incidence of dementia. It appears that most of cardiovascular risk factors, such as hypertension, diabetes mellitus, hypercholesterolemia, atrial fibrillation, and smoking are also risk factors for AD and not exclusively for VD [1–7]. Recent studies present us with new data connecting vascular risk factors and dementia. Atrial fibrillation, hypertension, and angina are shown to be associated with greater cognitive decline. These modifiable risk factors may become a greater point of interest in secondary prevention of dementia [8]. The Nun study done in 1997 showed a higher prevalence of dementia among stroke patients with pathologically proven Alzheimer's disease than in those without stroke [9]. Arterial stiffness is a clinical indicator of high pulse pressure [10]. One hypothesis is that functional changes of the arterial system may
☆ Note: This study is a result of a scientific project: The role of vascular risk factors in pathogenesis of Alzheimer's disease, supported by the Ministry of Science, Education and Sports of the Republic of Croatia (No:134-134-0036-0035). ⁎ Corresponding author. E-mail address: [email protected] (V. Demarin). 0022-510X/$ – see front matter © 2009 Published by Elsevier B.V. doi:10.1016/j.jns.2009.02.330
be involved in the pathogenesis of dementia. Specific measures of large artery structure and function — such as aorto-femoral or brachial-ankle pulse wave velocity (PWV) can be regarded as useful markers of subclinical vascular disease and are reliable predictors of vascular accidents such as stroke. Pulse wave analysis measures arterial stiffness between two points of the arterial tree. Ultrasound technique is used to identify the approaching arterial pulse and measure the velocity of a pulse wave. This method is considered a “golden standard” in arterial stiffness measurement. It allows for the detection of pathology prior to the appearance of morphological changes of the vasculature [10]. Arterial beta stiffness index of common carotid artery is a parameter that directly indicates stiffness of local arterial wall [10]. It was selected as a potential risk factor for increased stroke occurrence. As the vascular component appears to be significant in both AD and VAD, in this pilot study we aimed to further explore vascular characteristics of patients with both types of cognitive decline using non-invasive neurosonological methods. A neurosonological method widely used to this day is IMT measurement [3]. IMT is a noninvasive tool for assessing subclinical atherosclerosis. Carotid IMT is a marker of generalized atherosclerosis and is continuously associated with future vascular incidents such as stroke, cardiovascular and peripheral vascular disease [11].
42
S. Morović et al. / Journal of the Neurological Sciences 283 (2009) 41–43
2. Patients and methods
3. Results
This study was performed on 38 individuals who were fully informed about the procedure. There were 16 patients diagnosed with Alzheimer's disease (AD; 8 women, 8 men, aged 72.19 ± 6.86 years) and 22 patients diagnosed with vascular dementia (VAD; 14 women, 8 men, aged 70.20 ± 15.50 years). After taking the patient's history, vascular risk factors were extracted. Blood pressure measurements were taken three times with 10 min pauses for an accurate assessment, and the mean value was used in the study. Electrodes used for tracking cardiac cycles were placed on both hands. We also calculated body-mass index (BMI) to categorize patients accordingly. Vascular risk factors were assessed and ultrasound measurements on the common carotid artery (CCA) were performed using Aloka ProSound ALPHA 10 with a 13 MHz linear probe. Measurements performed on the common carotid artery were measurement of intima–media thickness (IMT), arterial beta stiffness index, pulse pressure measurement and lumen diameters. All measurements were done in a supine position with head elevated up to 45°, and tilted to the either side for 30°, depending on the side examined. B mode and M mode examinations were made 1.5 cm proximal to the carotid bifurcation on the far wall of the common carotid artery (CCA) on both sides. The IMT measurement was done following the Mannheim carotid intima–media thickness consensus [12]. The results were expressed as arithmetic means of measurements taken during three cardiac cycles. IMT measurement was done on the far wall during diastole. All IMT measurements were done by the same sonographers. The diameter was measured as the distance between two media– adventitia points on far and near wall. Arterial ß stiffness was measured automatically by “eTRACKING” software. Hypertension was considered to be present when the subject's systolic blood pressure was consistently 140 mmHg or greater, and/or the diastolic blood pressure is consistently 90 mmHg or greater. Diabetes mellitus was considered to be present in subjects with recurrent or persistent hyperglycemia, who had fasting a plasma glucose level at or above 7.0 mmol/l, plasma glucose at or above 11.1 mmol/l 2 h after glucose tolerance test, and/or random plasma glucose at or above 11.1 mmol/l. Hyper lipidemia was considered to be present when total serum cholesterol values exceeded 5.0 mmol/l. Presence of atrial fibrillation was confirmed by EKG monitoring. Neuroimaging by computerized tomography was used to help differentiate VAD from AD. Bilateral multiple infarcts were located in the dominant hemisphere and limbic structures, multiple lacunar strokes, or periventricular white matter lesions extending into the deep white matter. The lack of cerebrovascular lesions on CT scans was used as evidence against vascular etiology [13].
Among AD patients there were 5 with arterial hypertension (AH), 3 with atrial fibrillation (AF), 2 with diabetes mellitus (DM), 6 with hyper lipidemia and 1 was a smoker. Nineteen VAD patients had AH, 6 had AF, 12 had hyper lipidemia and one was diabetic. We found no statistically significant differences between the groups regarding average body mass index (BMI), blood pressure, pulse pressure, intima–media thickness (IMT), CCA diameter or arterial beta stiffness indices. However, the trend of BMI increase, slight blood and pulse pressure decrease, CCA diameter increase and beta stiffness index increase was noted in VAD patients (Table 1).
Table 1 Vascular characteristics and risk factors of patients diagnosed with vascular dementia (VAD) and Alzheimer's disease (AD).
38 patients Average age No. of hypertensive pts. Atrial fibrillation Diabetes mellitus Hyper lipidemia No. of smokers Average BMI Average RR mmHg Average pulse pressure mm Hg Average IMT mm Average CCA diameter Average beta stiffness
VAD
AD
22 (14 women, 8 men) 70.20 ± 15.50 19 6 1 12 0 26.98 ± 3.61 kg/m2 (NS) 135.23±17.62/78.50±9.95 (NS) 56.73 ± 13.08 (NS)
16 (8 women, 8 men) 72.19 ± 6.86 5 3 2 6 1 24.98 ± 4.07 kg/m2 136.06±24.48/78.56±16.93 57.50 ± 16.93
0.84 ± 0.32 (p b 0.05) (NS) 8.86 ± 1.44 (right CCA) 8.43 ± 1.41 (left CCA) (NS) 11.29 ± 4.73 (right CCA) 11.75 ± 6.55 (left CCA) (NS)
0.83 ± 0.18 8.31 ± 1.38 (right CCA) 8.29 ± 1.16 (left CCA) 9.91 ± 5.27 (right CCA) 11.31 ± 6.66 (left CCA)
(NS) refers to comparison of VAD and AD.
4. Discussion Even though there was no significant difference found among the two explored subgroups of patients with dementia, our investigation pointed towards some differences in vascular characteristics among AD and VAD patients. Even though this study was limited by a small number of patients, it showed a tendency of greater systolic and diastolic diameters noted in VAD as well as greater stiffness. It was recently pointed out that while evidence exists that cardiovascular risk factors increase risk of AD, there is not as much evidence on their influence on progression of AD once the diagnosis is established [8]. A recent population-based study suggests some cardiovascular risk factors are associated with more rapid progression of AD than others. Atrial fibrillation, systolic hypertension, and angina were associated with a more rapid cognitive decline than history of coronary artery bypass graft surgery, diabetes or antihypertensive medications [8]. Because some of the cardiovascular risk factors are modifiable [7], investigating the mechanisms by which they contribute to AD pathology and the manifestation of dementia has implications in prevention. Studies suggest that physical and total activity in midlife, diet and mild to moderate alcohol consumption are protective against AD [14]. In view of the vascular component of dementia, increased intima–media thickness measurement should be carefully assessed as a risk factor [15]. Since IMT is associated with hypertension and responds well to treatment of hypertension [7], it should be considered when assessing cognition. IMT measured at the time of stroke is predictive of cognitive impairment 1 year later [15]. Pulse wave velocity (PWV), a parameter of arterial stiffness, is associated with cognitive impairment and with a greater personal dependency, independently of major modifiable cerebrovascular risk factors [16]. This parameter is even more sensitive to vascular changes than IMT itself, because changes can be caught before clinical manifestation of atherosclerotic disease. Hanon et al. showed that higher PWV is associated with poorer cognitive function [17]. This study suggests that functional changes of the arterial system could be involved in the onset of dementia [17]. A study done in Japan showed that arterial stiffness assessed by pulse wave velocity was significantly and independently associated with the MMSE score in aged individuals [18]. A study done more than a decade ago (the Rotterdam study) investigated cardiovascular disease and cognitive function in the elderly. This study showed poorer cognitive function with increasing age and lower educational level [19]. The Rotterdam study also established a link between vascular events and atherosclerosis with poorer cognitive performance regardless of age and education. Despite today's point of view, only additional, well designed studies will clarify if dementia and vascular disease are two separate pathological processes, or if they represent two presentations of the same pathological process [9]. Also, greater emphasis must be put on primary and secondary prevention of dementia [20]. Therapy is most effective when initiated while individuals are still asymptomatic or show mild cognitive impairment. Many clinical trials are being developed in hope of early identification of individuals who will
S. Morović et al. / Journal of the Neurological Sciences 283 (2009) 41–43
eventually develop AD but don't yet show pathologic hallmarks, and those who already have the disease present but without clinical manifestations [20]. 5. Conclusion Our study suggests a tendency of greater systolic and diastolic diameters noted in VAD. We also noted greater arterial stiffness in patients diagnosed with vascular dementia in comparison to patients with Alzheimer's disease, especially when measured in the right CCA. This indicates that VAD patients may have more prominent vascular changes that may help differentiate the type of dementia and further monitor these individuals. Further studies on a larger number of patients are needed support this evidence. References [1] Siuda J, Gorzkowska A, Opala G, Ochudlo S. Vascular risk factors and intensity of cognitive dysfunction in MCI. J Neurol Sci 2007:1–8. [2] Hofman A, Ott A, Breteler MM. Atherosclerosis, apolipoprotein E and prevalence of dementia and Alzheimer's disease in the Rotterdam study. Lancet 1997;349:151–4. [3] Sofrizzi V, Panza F, Colacicco AM, D'Introno A, Capurso C, Torres F. Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology 2004;63:1882–91. [4] Morris J. Mild cognitive impairment and preclinical Alzheimer's disease. Geriatrics 2005:9–14. [5] Yener GG, Ozturk V, Uzunel F. Diagnosis profile and comparison of risk factors in major types of dementia: a hospital based study. J Neurol Sci 2004;21:4–8. [6] Kivipelto M, Helkala T, Hanninen T, Laakso MP, Hallikainen M, Alhainen K. Midlife vascular risk factors and late-life Alzheimer's disease. Ann Intern Med 2002;137:3. [7] Demarin V, Lovrenčić-Huzjan A, Trkanjec Z, Vuković V, Vargek-Solter V, Šerić V, et al. Recommendations for stroke management 2006 update. Acta clin Croat 2006;45:219–85.
43
[8] Mielke MM, Rosenberg PB, Tschanz J, Cook L, Corcoran C, Hayden KM, et al. Vascular factors predict rate of progression in Alzheimer disease. Neurology 2007;69:1850–8. [9] Sondown DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer's disease. The Nun study. JAMA 1997;277:813–7. [10] Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;27:2588–605. [11] Brenner DA, Alexandrov AV. Alheimer's disease: the vascular connection. Int J Stroke 2007;2:243–4. [12] Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim carotid intima–media thickness consensus (2004–2006). Cerebrovasc Dis 2007;23:75–80 Published online: November 14, 2006. [13] Diagnostic and statistical manual of mental disorders. DSM-IV™, International Version with ICD-10 Codes. Fourth Edition. Washington, DC: American Psychiatric Association; 1995. Croatian translation. Jastrebarsko: Naklada Slap; 1996. p. 144–50. [14] Jurašić MJ, Lovrenčić Huzjan A, Bedeković Roje M, Demarin V. How to monitor vascular aging with an ultrasound. J Neurol Sci 2007:1–9. [15] Spence JD. Carotid intima–media thickness and cognitive decline: what does it mean for prevention of dementia? J Neurol Sci 2004;223(2):103–5. [16] Scuteri A, Brancati AM, Gianni W, Assisi A, Volpe M. Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: a pilot study. J Hypertens 2005;23:1211–6. [17] Hanon O, Haulon SH, Lenoir S, Seux ML, Rigaud AS, Safar M, et al. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke 2005;36:2193–7. [18] Fukuhara M, Matsumura K, Ansai T, Takata Y, Sonoki K, Akifusa S, et al. Prediction of cognitive function by arterial stiffness in the very elderly. Circ J 2006;70:756–61. [19] Breteler MMB, Claus JJ, Grobbee DE, Hofman A. Cardiovascular disease and distribution of cognitive function in elderly people: the Rotterdam study. BMJ 1994;308:1604–8. [20] Cummings JL, Doody R, Clark C. Disease-modifying therapies for Alzheimer disease—challenges to early intervention. Neurology 2007;69:1622–35.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Vascular characteristics of patients with dementia☆ Sandra Morović, Miljenka-Jelena Jurašić, Irena Martinić Popović, Vesna Šerić, Marijana Lisak, Vida Demarin ⁎ University Department of Neurology, Sestre Milosrdnice University Hospital, Vinogradska 29, Zagreb, Croatia
a r t i c l e
i n f o
Available online 16 April 2009 Keywords: Dementia-vascular Alzheimer disease Arterial stiffness Vascular ultrasound
a b s t r a c t Arterial beta stiffness index is a potential risk factor for increased stroke occurrence. Vascular component appears to be significant in both Alzheimer's disease (AD) and vascular dementia (VAD). We aimed to further explore vascular characteristics of patients with both types of cognitive decline using non-invasive neurosonological methods. There were 38 patients; 16 diagnosed with AD and 22 with VAD. Vascular risk factors were assessed and ultrasound measurements on common carotid artery (CCA) were performed using Aloka ProSound ALPHA 10 with 13 MHz linear probe. Among AD patients there were 5 with arterial hypertension (AH), 3 with atrial fibrillation (AF), 2 with diabetes mellitus (DM), 6 with hyper lipidemia and 1 smoker. Nineteen VAD patients had AH, 6 had AF, 12 had hyper lipidemia and one was diabetic. We found no statistically significant differences between groups regarding average body mass index (BMI), blood pressure, pulse pressure, intima–media thickness (IMT), CCA diameter or arterial beta stiffness indices. However, the trend of BMI increase, slight blood and pulse pressure decrease, CCA diameter increase and beta stiffness index increase was noted in VAD patients. Even though there was no significant difference found among two explored subgroups of patients with dementia, there was a tendency of greater systolic and diastolic diameters noted in VAD as well as greater stiffness, especially when measured in the right CCA. This indicates that VAD patients may have more prominent vascular changes that may help differentiate the type of dementia and further monitor these individuals. Further studies on a larger number of patients are needed support this evidence. © 2009 Published by Elsevier B.V.
1. Introduction Impaired cognition sometimes accompanies ageing. As populations grow older, so does the increase in incidence of dementia. It appears that most of cardiovascular risk factors, such as hypertension, diabetes mellitus, hypercholesterolemia, atrial fibrillation, and smoking are also risk factors for AD and not exclusively for VD [1–7]. Recent studies present us with new data connecting vascular risk factors and dementia. Atrial fibrillation, hypertension, and angina are shown to be associated with greater cognitive decline. These modifiable risk factors may become a greater point of interest in secondary prevention of dementia [8]. The Nun study done in 1997 showed a higher prevalence of dementia among stroke patients with pathologically proven Alzheimer's disease than in those without stroke [9]. Arterial stiffness is a clinical indicator of high pulse pressure [10]. One hypothesis is that functional changes of the arterial system may
☆ Note: This study is a result of a scientific project: The role of vascular risk factors in pathogenesis of Alzheimer's disease, supported by the Ministry of Science, Education and Sports of the Republic of Croatia (No:134-134-0036-0035). ⁎ Corresponding author. E-mail address: [email protected] (V. Demarin). 0022-510X/$ – see front matter © 2009 Published by Elsevier B.V. doi:10.1016/j.jns.2009.02.330
be involved in the pathogenesis of dementia. Specific measures of large artery structure and function — such as aorto-femoral or brachial-ankle pulse wave velocity (PWV) can be regarded as useful markers of subclinical vascular disease and are reliable predictors of vascular accidents such as stroke. Pulse wave analysis measures arterial stiffness between two points of the arterial tree. Ultrasound technique is used to identify the approaching arterial pulse and measure the velocity of a pulse wave. This method is considered a “golden standard” in arterial stiffness measurement. It allows for the detection of pathology prior to the appearance of morphological changes of the vasculature [10]. Arterial beta stiffness index of common carotid artery is a parameter that directly indicates stiffness of local arterial wall [10]. It was selected as a potential risk factor for increased stroke occurrence. As the vascular component appears to be significant in both AD and VAD, in this pilot study we aimed to further explore vascular characteristics of patients with both types of cognitive decline using non-invasive neurosonological methods. A neurosonological method widely used to this day is IMT measurement [3]. IMT is a noninvasive tool for assessing subclinical atherosclerosis. Carotid IMT is a marker of generalized atherosclerosis and is continuously associated with future vascular incidents such as stroke, cardiovascular and peripheral vascular disease [11].
42
S. Morović et al. / Journal of the Neurological Sciences 283 (2009) 41–43
2. Patients and methods
3. Results
This study was performed on 38 individuals who were fully informed about the procedure. There were 16 patients diagnosed with Alzheimer's disease (AD; 8 women, 8 men, aged 72.19 ± 6.86 years) and 22 patients diagnosed with vascular dementia (VAD; 14 women, 8 men, aged 70.20 ± 15.50 years). After taking the patient's history, vascular risk factors were extracted. Blood pressure measurements were taken three times with 10 min pauses for an accurate assessment, and the mean value was used in the study. Electrodes used for tracking cardiac cycles were placed on both hands. We also calculated body-mass index (BMI) to categorize patients accordingly. Vascular risk factors were assessed and ultrasound measurements on the common carotid artery (CCA) were performed using Aloka ProSound ALPHA 10 with a 13 MHz linear probe. Measurements performed on the common carotid artery were measurement of intima–media thickness (IMT), arterial beta stiffness index, pulse pressure measurement and lumen diameters. All measurements were done in a supine position with head elevated up to 45°, and tilted to the either side for 30°, depending on the side examined. B mode and M mode examinations were made 1.5 cm proximal to the carotid bifurcation on the far wall of the common carotid artery (CCA) on both sides. The IMT measurement was done following the Mannheim carotid intima–media thickness consensus [12]. The results were expressed as arithmetic means of measurements taken during three cardiac cycles. IMT measurement was done on the far wall during diastole. All IMT measurements were done by the same sonographers. The diameter was measured as the distance between two media– adventitia points on far and near wall. Arterial ß stiffness was measured automatically by “eTRACKING” software. Hypertension was considered to be present when the subject's systolic blood pressure was consistently 140 mmHg or greater, and/or the diastolic blood pressure is consistently 90 mmHg or greater. Diabetes mellitus was considered to be present in subjects with recurrent or persistent hyperglycemia, who had fasting a plasma glucose level at or above 7.0 mmol/l, plasma glucose at or above 11.1 mmol/l 2 h after glucose tolerance test, and/or random plasma glucose at or above 11.1 mmol/l. Hyper lipidemia was considered to be present when total serum cholesterol values exceeded 5.0 mmol/l. Presence of atrial fibrillation was confirmed by EKG monitoring. Neuroimaging by computerized tomography was used to help differentiate VAD from AD. Bilateral multiple infarcts were located in the dominant hemisphere and limbic structures, multiple lacunar strokes, or periventricular white matter lesions extending into the deep white matter. The lack of cerebrovascular lesions on CT scans was used as evidence against vascular etiology [13].
Among AD patients there were 5 with arterial hypertension (AH), 3 with atrial fibrillation (AF), 2 with diabetes mellitus (DM), 6 with hyper lipidemia and 1 was a smoker. Nineteen VAD patients had AH, 6 had AF, 12 had hyper lipidemia and one was diabetic. We found no statistically significant differences between the groups regarding average body mass index (BMI), blood pressure, pulse pressure, intima–media thickness (IMT), CCA diameter or arterial beta stiffness indices. However, the trend of BMI increase, slight blood and pulse pressure decrease, CCA diameter increase and beta stiffness index increase was noted in VAD patients (Table 1).
Table 1 Vascular characteristics and risk factors of patients diagnosed with vascular dementia (VAD) and Alzheimer's disease (AD).
38 patients Average age No. of hypertensive pts. Atrial fibrillation Diabetes mellitus Hyper lipidemia No. of smokers Average BMI Average RR mmHg Average pulse pressure mm Hg Average IMT mm Average CCA diameter Average beta stiffness
VAD
AD
22 (14 women, 8 men) 70.20 ± 15.50 19 6 1 12 0 26.98 ± 3.61 kg/m2 (NS) 135.23±17.62/78.50±9.95 (NS) 56.73 ± 13.08 (NS)
16 (8 women, 8 men) 72.19 ± 6.86 5 3 2 6 1 24.98 ± 4.07 kg/m2 136.06±24.48/78.56±16.93 57.50 ± 16.93
0.84 ± 0.32 (p b 0.05) (NS) 8.86 ± 1.44 (right CCA) 8.43 ± 1.41 (left CCA) (NS) 11.29 ± 4.73 (right CCA) 11.75 ± 6.55 (left CCA) (NS)
0.83 ± 0.18 8.31 ± 1.38 (right CCA) 8.29 ± 1.16 (left CCA) 9.91 ± 5.27 (right CCA) 11.31 ± 6.66 (left CCA)
(NS) refers to comparison of VAD and AD.
4. Discussion Even though there was no significant difference found among the two explored subgroups of patients with dementia, our investigation pointed towards some differences in vascular characteristics among AD and VAD patients. Even though this study was limited by a small number of patients, it showed a tendency of greater systolic and diastolic diameters noted in VAD as well as greater stiffness. It was recently pointed out that while evidence exists that cardiovascular risk factors increase risk of AD, there is not as much evidence on their influence on progression of AD once the diagnosis is established [8]. A recent population-based study suggests some cardiovascular risk factors are associated with more rapid progression of AD than others. Atrial fibrillation, systolic hypertension, and angina were associated with a more rapid cognitive decline than history of coronary artery bypass graft surgery, diabetes or antihypertensive medications [8]. Because some of the cardiovascular risk factors are modifiable [7], investigating the mechanisms by which they contribute to AD pathology and the manifestation of dementia has implications in prevention. Studies suggest that physical and total activity in midlife, diet and mild to moderate alcohol consumption are protective against AD [14]. In view of the vascular component of dementia, increased intima–media thickness measurement should be carefully assessed as a risk factor [15]. Since IMT is associated with hypertension and responds well to treatment of hypertension [7], it should be considered when assessing cognition. IMT measured at the time of stroke is predictive of cognitive impairment 1 year later [15]. Pulse wave velocity (PWV), a parameter of arterial stiffness, is associated with cognitive impairment and with a greater personal dependency, independently of major modifiable cerebrovascular risk factors [16]. This parameter is even more sensitive to vascular changes than IMT itself, because changes can be caught before clinical manifestation of atherosclerotic disease. Hanon et al. showed that higher PWV is associated with poorer cognitive function [17]. This study suggests that functional changes of the arterial system could be involved in the onset of dementia [17]. A study done in Japan showed that arterial stiffness assessed by pulse wave velocity was significantly and independently associated with the MMSE score in aged individuals [18]. A study done more than a decade ago (the Rotterdam study) investigated cardiovascular disease and cognitive function in the elderly. This study showed poorer cognitive function with increasing age and lower educational level [19]. The Rotterdam study also established a link between vascular events and atherosclerosis with poorer cognitive performance regardless of age and education. Despite today's point of view, only additional, well designed studies will clarify if dementia and vascular disease are two separate pathological processes, or if they represent two presentations of the same pathological process [9]. Also, greater emphasis must be put on primary and secondary prevention of dementia [20]. Therapy is most effective when initiated while individuals are still asymptomatic or show mild cognitive impairment. Many clinical trials are being developed in hope of early identification of individuals who will
S. Morović et al. / Journal of the Neurological Sciences 283 (2009) 41–43
eventually develop AD but don't yet show pathologic hallmarks, and those who already have the disease present but without clinical manifestations [20]. 5. Conclusion Our study suggests a tendency of greater systolic and diastolic diameters noted in VAD. We also noted greater arterial stiffness in patients diagnosed with vascular dementia in comparison to patients with Alzheimer's disease, especially when measured in the right CCA. This indicates that VAD patients may have more prominent vascular changes that may help differentiate the type of dementia and further monitor these individuals. Further studies on a larger number of patients are needed support this evidence. References [1] Siuda J, Gorzkowska A, Opala G, Ochudlo S. Vascular risk factors and intensity of cognitive dysfunction in MCI. J Neurol Sci 2007:1–8. [2] Hofman A, Ott A, Breteler MM. Atherosclerosis, apolipoprotein E and prevalence of dementia and Alzheimer's disease in the Rotterdam study. Lancet 1997;349:151–4. [3] Sofrizzi V, Panza F, Colacicco AM, D'Introno A, Capurso C, Torres F. Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology 2004;63:1882–91. [4] Morris J. Mild cognitive impairment and preclinical Alzheimer's disease. Geriatrics 2005:9–14. [5] Yener GG, Ozturk V, Uzunel F. Diagnosis profile and comparison of risk factors in major types of dementia: a hospital based study. J Neurol Sci 2004;21:4–8. [6] Kivipelto M, Helkala T, Hanninen T, Laakso MP, Hallikainen M, Alhainen K. Midlife vascular risk factors and late-life Alzheimer's disease. Ann Intern Med 2002;137:3. [7] Demarin V, Lovrenčić-Huzjan A, Trkanjec Z, Vuković V, Vargek-Solter V, Šerić V, et al. Recommendations for stroke management 2006 update. Acta clin Croat 2006;45:219–85.
43
[8] Mielke MM, Rosenberg PB, Tschanz J, Cook L, Corcoran C, Hayden KM, et al. Vascular factors predict rate of progression in Alzheimer disease. Neurology 2007;69:1850–8. [9] Sondown DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer's disease. The Nun study. JAMA 1997;277:813–7. [10] Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;27:2588–605. [11] Brenner DA, Alexandrov AV. Alheimer's disease: the vascular connection. Int J Stroke 2007;2:243–4. [12] Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim carotid intima–media thickness consensus (2004–2006). Cerebrovasc Dis 2007;23:75–80 Published online: November 14, 2006. [13] Diagnostic and statistical manual of mental disorders. DSM-IV™, International Version with ICD-10 Codes. Fourth Edition. Washington, DC: American Psychiatric Association; 1995. Croatian translation. Jastrebarsko: Naklada Slap; 1996. p. 144–50. [14] Jurašić MJ, Lovrenčić Huzjan A, Bedeković Roje M, Demarin V. How to monitor vascular aging with an ultrasound. J Neurol Sci 2007:1–9. [15] Spence JD. Carotid intima–media thickness and cognitive decline: what does it mean for prevention of dementia? J Neurol Sci 2004;223(2):103–5. [16] Scuteri A, Brancati AM, Gianni W, Assisi A, Volpe M. Arterial stiffness is an independent risk factor for cognitive impairment in the elderly: a pilot study. J Hypertens 2005;23:1211–6. [17] Hanon O, Haulon SH, Lenoir S, Seux ML, Rigaud AS, Safar M, et al. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke 2005;36:2193–7. [18] Fukuhara M, Matsumura K, Ansai T, Takata Y, Sonoki K, Akifusa S, et al. Prediction of cognitive function by arterial stiffness in the very elderly. Circ J 2006;70:756–61. [19] Breteler MMB, Claus JJ, Grobbee DE, Hofman A. Cardiovascular disease and distribution of cognitive function in elderly people: the Rotterdam study. BMJ 1994;308:1604–8. [20] Cummings JL, Doody R, Clark C. Disease-modifying therapies for Alzheimer disease—challenges to early intervention. Neurology 2007;69:1622–35.