Original Paper Received: February 4, 2014 Accepted: May 15, 2014 Published online: September 2, 2014
Cerebrovasc Dis 2014;38:24–30 DOI: 10.1159/000363620
Diffusion Tensor Imaging, Intracranial Vascular Resistance and Cognition in Middle-Aged Asymptomatic Subjects Jorge López-Olóriz a, b Elena López-Cancio c Juan F. Arenillas d María Hernández c Laura Dorado c Rosalía Dacosta-Aguayo a Maite Barrios e Juan José Soriano-Raya a Júlia Miralbell a, b Núria Bargalló f, g Cynthia Cáceres c Pere Torán h, i Maite Alzamora h, j Antonio Dávalos c Maria Mataró a, b
a
Department of Psychiatry and Clinical Psychobiology, b Institute for Brain, Cognition and Behavior (IR3C), Universitat de Barcelona, Barcelona, c Department of Neurosciences, Hospital Universitari Germans Trias I Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, d Stroke Unit, Department of Neurology, Hospital Clínico Universitario, Valladolid, e Department of Methodology of Behavioural Sciences, Universitat de Barcelona, f Radiology Department, Image Diagnosis Center, Hospital Clínic, g Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, h Primary Healthcare Research Support Unit Metropolitana Nord, ICS-IDIAP Jordi Gol, i Primary Healthcare Centre Gatassa, Mataró, Barcelona, j Primary Healthcare Centre Riu Nord-Riu Sud, Santa Coloma de Gramenet, Barcelona, Spain
Key Words Vascular cognitive impairment · Pulsatility index · Vascular resistance · Diffusion tensor imaging
Abstract Background: The contribution of traditional vascular risk factors to cognitive impairment and dementia is well known. However, in order to obtain possible targets for prevention of vascular cognitive impairment (VCI), it may be important to identify other early and noninvasive markers in asymptomatic middle-aged adults. The calculation of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique to assess increased distal resistance to blood flow. This study aims to assess the relationship between MCA-PI, microstructural white matter (WM) integrity and cognition in a middleaged asymptomatic population. Methods: Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were includ-
© 2014 S. Karger AG, Basel 1015–9770/14/0381–0024$39.50/0 E-Mail [email protected] www.karger.com/ced
ed. Subjects were 50–65 years old, free from dementia and without history of vascular disease. Transcranial color-coded duplex ultrasound examination was performed to assess MCA-PI as a measure of vascular resistance. WM integrity was evaluated by fractional anisotropy (FA) measurements of diffusion tensor images (DTI) acquired on a 3T-MRI. The neuropsychological battery was specifically selected to be sensitive to VCI, and included tests that were grouped into six cognitive domains: executive functioning, attention, verbal fluency, memory, visuospatial skills and psychomotor speed. A multivariate linear regression model adjusted for age, gender, years of education, diabetes and hypertension was performed. Results: MCA-PI was significantly associated with WM disintegration in different tracts (fornix, corticospinal and anterior thalamic), all p < 0.05 uncorrected. Both mean MCA-PI and mean FA of those significant tracts were independently associated with poor performance in attention, psychomotor speed, and visuospatial skills after adjustment for age, gender, years of education, and vascular risk factors (all p < 0.05). MCA-PI was independently associated with
Dra. Maria Mataró Department of Psychiatry and Clinical Psychobiology Universitat de Barcelona Passeig de la Vall d’Hebron 171, ES–08035 Barcelona (Spain) E-Mail mmataro @ ub.edu
Downloaded by: NYU Medical Center Library 128.122.253.212 - 10/11/2014 8:02:25 AM
Introduction
Vascular risk factors (VRF) have been consistently related to cognitive impairment and dementia [1–3]. Vascular Cognitive Impairment (VCI) is associated with stroke and with subclinical ischemic brain lesions [4], and there is increasing interest in its relevance and contribution to cognitive dysfunction [5]. However, there can be vascular cognitive decline even in the absence of clinically detectable precipitating events [6, 7]. MRI studies including diffusion tensor imaging (DTI) can assess microstructural changes in the normal-appearing white matter (WM) before they can be visualized using conventional MRI. These early changes have been associated with cognitive function, regardless of WM atrophy and WM lesion volume [8]. Risk markers for VCI are generally the same as traditional risk factors for stroke [4]. It may be important to identify other early and noninvasive markers of VCI in asymptomatic middle-aged adults, in order to obtain possible targets for prevention. The measurement of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique. PI is an indicator of increased distal resistance to blood flow [9] and it has been associated with microvascular dysfunction [10]. MCA-PI offers a picture of the structure and function of cerebral small vessels, less accessible to morphological studies. MCA-PI has also been evaluated in the field of cognitive impairment and dementia. MCA-PI is found to be related to Alzheimer disease [11, 12] and to WM lesions (WMLs) in hypertensive [13] and stroke patients [14, 15]. Mok et al. [16] found a relationship between MCA-PI and severe WML but not with lacunes or microbleeds in subjects older than 60 years. In a small group of hypertensive and diabetic elders, Purkayastha et al. [17] found an association between MCAPI and WMH, but not with miscrostructural brain changes measured by MRI-DTI. In the Barcelona-AsIA-Neuropsychology Study, including 747 asymptomatic subjects DTI, Intracranial Vascular Resistance and Cognition
with a wide age range (51–91 years), we found an independent association between MCA-PI and lower cognitive performance [18]. The relationship between MCA-PI and microstructural DTI-WM changes of concrete tracts in a population-based sample has never been explored. The aim of this study is to assess the association between a noninvasive cerebral ultrasound measurement, microstructural WM integrity and cognition in a middleaged asymptomatic population.
Methods Study Design and Sample Selection The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) Neuropsychology study is a population-based study that aims (1) to evaluate the associations of vascular risk factors, asymptomatic extra and intracranial atherosclerosis with cognition, and (2) to identify clinical features and biological mechanisms underlying these associations. For the present research, one hundred subjects aged 50 to 65, including subjects from low to high vascular risk according to the REGICOR score (the validated Spanish adaptation of the Framingham cardiovascular risk scale), were selected to undergo an extensive neuropsychological assessment, a complete extra and transcranial ultrasound study, and brain magnetic resonance imaging (MRI) within the next month after the baseline visit. Exclusion criteria were as follows: chronic neurological disease or severe psychiatric disorder; a Mini-Mental State Examination (MMSE) score
Cerebrovasc Dis 2014;38:24–30 DOI: 10.1159/000363620
Diffusion Tensor Imaging, Intracranial Vascular Resistance and Cognition in Middle-Aged Asymptomatic Subjects Jorge López-Olóriz a, b Elena López-Cancio c Juan F. Arenillas d María Hernández c Laura Dorado c Rosalía Dacosta-Aguayo a Maite Barrios e Juan José Soriano-Raya a Júlia Miralbell a, b Núria Bargalló f, g Cynthia Cáceres c Pere Torán h, i Maite Alzamora h, j Antonio Dávalos c Maria Mataró a, b
a
Department of Psychiatry and Clinical Psychobiology, b Institute for Brain, Cognition and Behavior (IR3C), Universitat de Barcelona, Barcelona, c Department of Neurosciences, Hospital Universitari Germans Trias I Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, d Stroke Unit, Department of Neurology, Hospital Clínico Universitario, Valladolid, e Department of Methodology of Behavioural Sciences, Universitat de Barcelona, f Radiology Department, Image Diagnosis Center, Hospital Clínic, g Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, h Primary Healthcare Research Support Unit Metropolitana Nord, ICS-IDIAP Jordi Gol, i Primary Healthcare Centre Gatassa, Mataró, Barcelona, j Primary Healthcare Centre Riu Nord-Riu Sud, Santa Coloma de Gramenet, Barcelona, Spain
Key Words Vascular cognitive impairment · Pulsatility index · Vascular resistance · Diffusion tensor imaging
Abstract Background: The contribution of traditional vascular risk factors to cognitive impairment and dementia is well known. However, in order to obtain possible targets for prevention of vascular cognitive impairment (VCI), it may be important to identify other early and noninvasive markers in asymptomatic middle-aged adults. The calculation of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique to assess increased distal resistance to blood flow. This study aims to assess the relationship between MCA-PI, microstructural white matter (WM) integrity and cognition in a middleaged asymptomatic population. Methods: Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were includ-
© 2014 S. Karger AG, Basel 1015–9770/14/0381–0024$39.50/0 E-Mail [email protected] www.karger.com/ced
ed. Subjects were 50–65 years old, free from dementia and without history of vascular disease. Transcranial color-coded duplex ultrasound examination was performed to assess MCA-PI as a measure of vascular resistance. WM integrity was evaluated by fractional anisotropy (FA) measurements of diffusion tensor images (DTI) acquired on a 3T-MRI. The neuropsychological battery was specifically selected to be sensitive to VCI, and included tests that were grouped into six cognitive domains: executive functioning, attention, verbal fluency, memory, visuospatial skills and psychomotor speed. A multivariate linear regression model adjusted for age, gender, years of education, diabetes and hypertension was performed. Results: MCA-PI was significantly associated with WM disintegration in different tracts (fornix, corticospinal and anterior thalamic), all p < 0.05 uncorrected. Both mean MCA-PI and mean FA of those significant tracts were independently associated with poor performance in attention, psychomotor speed, and visuospatial skills after adjustment for age, gender, years of education, and vascular risk factors (all p < 0.05). MCA-PI was independently associated with
Dra. Maria Mataró Department of Psychiatry and Clinical Psychobiology Universitat de Barcelona Passeig de la Vall d’Hebron 171, ES–08035 Barcelona (Spain) E-Mail mmataro @ ub.edu
Downloaded by: NYU Medical Center Library 128.122.253.212 - 10/11/2014 8:02:25 AM
Introduction
Vascular risk factors (VRF) have been consistently related to cognitive impairment and dementia [1–3]. Vascular Cognitive Impairment (VCI) is associated with stroke and with subclinical ischemic brain lesions [4], and there is increasing interest in its relevance and contribution to cognitive dysfunction [5]. However, there can be vascular cognitive decline even in the absence of clinically detectable precipitating events [6, 7]. MRI studies including diffusion tensor imaging (DTI) can assess microstructural changes in the normal-appearing white matter (WM) before they can be visualized using conventional MRI. These early changes have been associated with cognitive function, regardless of WM atrophy and WM lesion volume [8]. Risk markers for VCI are generally the same as traditional risk factors for stroke [4]. It may be important to identify other early and noninvasive markers of VCI in asymptomatic middle-aged adults, in order to obtain possible targets for prevention. The measurement of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique. PI is an indicator of increased distal resistance to blood flow [9] and it has been associated with microvascular dysfunction [10]. MCA-PI offers a picture of the structure and function of cerebral small vessels, less accessible to morphological studies. MCA-PI has also been evaluated in the field of cognitive impairment and dementia. MCA-PI is found to be related to Alzheimer disease [11, 12] and to WM lesions (WMLs) in hypertensive [13] and stroke patients [14, 15]. Mok et al. [16] found a relationship between MCA-PI and severe WML but not with lacunes or microbleeds in subjects older than 60 years. In a small group of hypertensive and diabetic elders, Purkayastha et al. [17] found an association between MCAPI and WMH, but not with miscrostructural brain changes measured by MRI-DTI. In the Barcelona-AsIA-Neuropsychology Study, including 747 asymptomatic subjects DTI, Intracranial Vascular Resistance and Cognition
with a wide age range (51–91 years), we found an independent association between MCA-PI and lower cognitive performance [18]. The relationship between MCA-PI and microstructural DTI-WM changes of concrete tracts in a population-based sample has never been explored. The aim of this study is to assess the association between a noninvasive cerebral ultrasound measurement, microstructural WM integrity and cognition in a middleaged asymptomatic population.
Methods Study Design and Sample Selection The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) Neuropsychology study is a population-based study that aims (1) to evaluate the associations of vascular risk factors, asymptomatic extra and intracranial atherosclerosis with cognition, and (2) to identify clinical features and biological mechanisms underlying these associations. For the present research, one hundred subjects aged 50 to 65, including subjects from low to high vascular risk according to the REGICOR score (the validated Spanish adaptation of the Framingham cardiovascular risk scale), were selected to undergo an extensive neuropsychological assessment, a complete extra and transcranial ultrasound study, and brain magnetic resonance imaging (MRI) within the next month after the baseline visit. Exclusion criteria were as follows: chronic neurological disease or severe psychiatric disorder; a Mini-Mental State Examination (MMSE) score
