Diffusion Tensor Imaging, Intracranial Vascular Resistance and Cognition in Middle-Aged Asymptomatic Subjects

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 middle-aged asymptomatic population. Methods: Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. 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 lower scores in all cognitive domains, except for visuospatial skills. Conclusions: Our data suggest that MCA-PI may be related to WM disintegration and early vascular cognitive impairment in middle-aged subjects. Although further prospective studies are needed to provide evidence for its validity in longitudinal studies, our results support the proposal of including MCA-PI as part of clinical assessment in order to identify targets for VCI prevention.

Middle Cerebral Artery Pulsatility Index is Associated with Cognitive Impairment in Lacunar Stroke

“…To the best of our knowledge, our study is the first to identify this association in patients with ischemic strokes. The results are however in accordance with those found by Lopez-Oloriz et al 31 in a study of asymptomatic participants between 50 and 65 years. Our mean PI value is higher than in this study.…”

Microstructural white matter changes mediate age‐related cognitive decline on the Montreal Cognitive Assessment (MoCA)

“…This is consistent with evidence that changes to cerebral vasculature more strongly affect cognitive processes that rely on frontal networks. For instance, López‐Olóriz et al () reported that increasing middle cerebral arterial pulsatility was linked to poorer executive function, attention, verbal fluency, memory, and processing speed. Knecht, Wersching, Lohmann, Berger, & Ringelstein () reported that up to 11% of age‐related changes in memory, executive function, attention, and verbal fluency were linked to systolic blood pressure.…”

“…Studies comparing WMH and DTI measures to quantify white matter structure highlight the greater sensitivity of DTI measures to individual differences in cognitive functioning, and especially processing speed and executive functioning (e.g., Kerchner et al, ; Nitkunan, Barrick, Charlton, Clark, & Markus, ; O'Sullivan et al, ; Salami, Eriksson, Nilsson, & Nyberg, ; Sasson, Doniger, Pasternak, Tarrasch, & Assaf, ; Shenkin et al, ). Indeed, recent studies suggest that changes in white matter microstructure may underlie age‐related decline in cognitive function on a range of neuropsychological tasks (e.g., Bendlin et al, ; Lopez‐Oloriz et al, ; Sullivan, Rohlfing, & Pfefferbaum, ; Vernooij et al, ; Zhuang et al, ) and experimental measures that target executive functioning (e.g., Madden, Spaniol et al, ; see Bennett & Madden, , for review). Moreover, white matter microstructural changes may explain the greater age‐related cognitive decline in the presence of cardiovascular risk factors (Kennedy & Raz, ; Maillard et al, ).…”

“…Measures of intracranial and intracerebral blood flow pulsatility have also been associated with white matter changes. Lopez‐Oloriz et al () measured middle cerebral artery (MCA) pulsatility index using transcranial ultrasound. MCA pulsatility was weakly associated with FA in clusters in the fornix, thalamic radiation, and corticospinal tract (i.e., did not survive familywise error rate correction).…”

Correlation Between Hippocampal Enlarged Perivascular Spaces and Cognition in Non-dementic Elderly Population

“…Impaired vascular circulation from any cause leads to cognitive impairment ( 18 , 19 ). The middle cerebral artery-pulsatility index (MCA-PI) is independently associated with cognitive impairment in middle-aged asymptomatic subjects ( 20 ). Patients with AD with higher posterior atrophy scores have worse performance on tasks of visuospatial and executive function ( 21 ).…”