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. 2017;60(1):243-252.
doi: 10.3233/JAD-170402.

Intracranial Arterial 4D Flow in Individuals with Mild Cognitive Impairment is Associated with Cognitive Performance and Amyloid Positivity

Sara E Berman  1   2   3 , Lindsay R Clark  4   1   5 , Leonardo A Rivera-Rivera  6 , Derek Norton  7 , Annie M Racine  1 , Howard A Rowley  1   8 , Barbara B Bendlin  4   1   5 , Kaj Blennow  9   10 , Henrik Zetterberg  9   10   11   12 , Cynthia M Carlsson  4   1   5 , Sanjay Asthana  4   1 , Patrick Turski  6   8 , Oliver Wieben  6   8 , Sterling C Johnson  4   1   5
Affiliations

Intracranial Arterial 4D Flow in Individuals with Mild Cognitive Impairment is Associated with Cognitive Performance and Amyloid Positivity

Sara E Berman et al. J Alzheimers Dis. 2017.

Abstract

It is becoming increasingly recognized that cerebrovascular disease is a contributing factor in the pathogenesis of Alzheimer's disease (AD). A unique 4D-Flow magnetic resonance imaging (MRI) technique, phase contrast vastly undersampled isotropic projection imaging (PC VIPR), enables examination of angiographic and quantitative metrics of blood flow in the arteries of the Circle of Willis within a single MRI acquisition. Thirty-eight participants with mild cognitive impairment (MCI) underwent a comprehensive neuroimaging protocol (including 4D-Flow imaging) and a standard neuropsychological battery. A subset of participants (n = 22) also underwent lumbar puncture and had cerebrospinal fluid (CSF) assayed for AD biomarkers. Cut-offs for biomarker positivity in CSF resulting from a receiver operating characteristic curve analysis of AD cases and controls from the larger Wisconsin Alzheimer's Disease Research Center cohort were used to classify MCI participants as biomarker positive or negative on amyloid-β (Aβ42), total-tau and total-tau/Aβ42 ratio. Internal carotid artery (ICA) and middle cerebral artery (MCA) mean flow were associated with executive functioning performance, with lower mean flow corresponding to worse performance. MCI participants who were biomarker positive for Aβ42 had lower ICA mean flow than did those who were Aβ42 negative. In sum, mean ICA and MCA arterial flow was associated with cognitive performance in participants with MCI and lower flow in the ICA was associated with amyloid positivity. This provides further evidence for vascular health as a contributing factor in the etiopathogenesis of AD, and could represent a point to intervene in the disease process.

Keywords: Aging; Alzheimer’s disease; cerebrovascular disease; mild cognitive impairment.

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Figures

Figure 1
Figure 1. Greater mean flow in the ICA and MCA correlates with better executive functioning performance
(A) ICA mean flow in participants with MCI is on the x-axis, and executive function composite score adjusted for covariates (age, gender, interval between MRI and neuropsychological testing, and years of education) is on the y-axis. A higher composite Z-score indicates better performance (N=38, p<.001); (B) MCA mean flow in participants with MCI is on the x-axis and executive function composite score adjusted for covariates (age, gender, interval between MRI and neuropsychological testing, and years of education) is on the y-axis (N=35, p<.001).
Figure 2
Figure 2. Amyloid positivity is associated with reduced blood flow in the ICA
MCI participants who were amyloid positive (Aβ42 ≤ 471.54 ng/L) had reduced mean blood flow measured in the distal petrous portion of the ICA. Biomarker positivity is plotted on the x-axis and unadjusted ICA mean flow data is on the y-axis (N=22, p = 0.034).
See this image and copyright information in PMC

References

    1. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270–279. - PMC - PubMed
    1. Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL, de Leon M, Feldman H, Ganguli M, Hampel H, Scheltens P, Tierney MC, Whitehouse P, Winblad B International Psychogeriatric Association Expert Conference on mild cognitive i. Mild cognitive impairment. Lancet. 2006;367:1262–1270. - PubMed
    1. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5:228–234. - PubMed
    1. Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, Freund-Levi Y, Tsolaki M, Minthon L, Wallin AK, Hampel H, Burger K, Pirttila T, Soininen H, Rikkert MO, Verbeek MM, Spiru L, Blennow K. Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 2009;8:619–627. - PubMed
    1. Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VM, Trojanowski JQ Alzheimer’s Disease Neuroimaging I. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol. 2009;65:403–413. - PMC - PubMed

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