BackgroundPatients with carotid artery occlusion (CAO) are vulnerable to cognitive impairment (CI). Anaemia is associated with CI in the general population. We hypothesized that lower haemoglobin... Show moreBackgroundPatients with carotid artery occlusion (CAO) are vulnerable to cognitive impairment (CI). Anaemia is associated with CI in the general population. We hypothesized that lower haemoglobin is associated with cognitive impairment (CI) in patients with CAO and that this association is accentuated by cerebral blood flow (CBF).Methods104 patients (mean age 66±8 years, 77% men) with complete CAO from the Heart-Brain Connection study were included. Anaemia was defined as haemoglobin < 12 g/dL for women and < 13 g/dL for men. Cognitive test results were standardized into z-scores (using a reference group) in four cognitive domains. Patients were classified as cognitively impaired when ≥ one domain was impaired. The association between lower haemoglobin and both cognitive domain z-scores and the presence of CI was assessed with adjusted (age, sex, education and ischaemic stroke) regression models. Total CBF (measured with phase contrast MRI) and the interaction term haemoglobin*CBF were additionally added to the analyses.ResultsAnaemia was present in 6 (6%) patients and was associated with CI (RR 2.54, 95% CI 1.36; 4.76). Lower haemoglobin was associated with the presence of CI (RR per minus 1 g/dL haemoglobin 1.15, 95% CI 1.02; 1.30). This association was strongest for the attention-psychomotor speed domain (RR for impaired attention-psychomotor speed functioning per minus 1 g/dL haemoglobin 1.27, 95% CI 1.09;1.47) and ß for attention-psychomotor speed z-scores per minus 1 g/dL haemoglobin -0.19, 95% CI -0.33; -0.05). Adjustment for CBF did not affect these results and we found no interaction between haemoglobin and CBF in relation to cognition.ConclusionLower haemoglobin concentrations are associated with CI in patients with complete CAO, particularly in the domain attention-psychomotor speed. CBF did not accentuate this association. If validated in longitudinal studies, haemoglobin might be a viable target to prevent cognitive deterioration in patients with CAO. Show less
In this thesis, multiple approaches have been investigated for the simultaneous acquisition of 4D angiography and perfusion images using arterial spin labeling (ASL) MRI. Time-encoded pseudo... Show moreIn this thesis, multiple approaches have been investigated for the simultaneous acquisition of 4D angiography and perfusion images using arterial spin labeling (ASL) MRI. Time-encoded pseudo-continuous (ASL) preparation was combined with multiple different readout modules, such as Look-Locker, Simultaneous multi-slice acquisition or a golden angle based non-Cartesian k-space trajectory to obtain high temporal resolution multi-time point data. These datasets were then used to improve the quantification of ASL signal and to obtain cerebral blood flow, arterial transit time and arterial blood volume maps. These quantitative maps hold the potential to provide important information in for example patients with stroke or Alzheimer’s disease. In addition, one of the assumptions within the two-component kinetic model to obtain these quantitative maps was investigated to study the separation of the macrovascular and perfusion component of the ASL signal. Show less
Brink, H. van den; Ferro, D.A.; Bresser, J. de; Bron, E.E.; Onkenhout, L.P.; Kappelle, L.J.; ... ; Heart-Brain Connection Consortium 2021
Cerebral cortical microinfarcts (CMI) are small ischemic lesions that are associated with cognitive impairment and probably have multiple etiologies. Cerebral hypoperfusion has been proposed as a... Show moreCerebral cortical microinfarcts (CMI) are small ischemic lesions that are associated with cognitive impairment and probably have multiple etiologies. Cerebral hypoperfusion has been proposed as a causal factor. We studied CMI in patients with internal carotid artery (ICA) occlusion, as a model for cerebral hemodynamic compromise. We included 95 patients with a complete ICA occlusion (age 66.2 +/- 8.3, 22% female) and 125 reference participants (age 65.5 +/- 7.4, 47% female). Participants underwent clinical, neuropsychological, and 3 T brain MRI assessment. CMI were more common in patients with an ICA occlusion (54%, median 2, range 1-33) than in the reference group (6%, median 0; range 1-7; OR 14.3; 95% CI 6.2-33.1; p<.001). CMI were more common ipsilateral to the occlusion than in the contralateral hemisphere (median 2 and 0 respectively; p<.001). In patients with CMI compared to patients without CMI, the number of additional occluded or stenosed cervical arteries was higher (p=.038), and cerebral blood flow was lower (B -6.2 ml/min/100 ml; 95% CI -12.0:-0.41; p=.036). In conclusion, CMI are common in patients with an ICA occlusion, particularly in the hemisphere of the occluded ICA. CMI burden was related to the severity of cervical arterial compromise, supporting a role of hemodynamics in CMI etiology. Show less
One of the pathological hallmarks of Alzheimer's disease is amyloid‑β accumulation in the parenchymal brain tissue. Amyloid‑β is also found in the vessel wall of patients with cerebral amyloid... Show moreOne of the pathological hallmarks of Alzheimer's disease is amyloid‑β accumulation in the parenchymal brain tissue. Amyloid‑β is also found in the vessel wall of patients with cerebral amyloid angiopathy (CAA). These pathological accumulations of the amyloid‑β peptide are referred to as amyloidosis. Both patients with AD and CAA also commonly show cerebrovascular dysfunction. The aim of this thesis was to improve our understanding of the relation between cerebrovascular dysfunction and amyloidosis. To that end, cerebrovascular function measurements were designed and carried out in mouse models of cerebral amyloidosis. Chapter 2 and 3 show improvements of the current techniques to measure cerebrovascular function in mice. Surprisingly however, no difference was found in cerebrovascular function in two different models of amyloidosis, as shown in chapter 4 and 5. Possible explanations of the negative findings are further discussed in chapter 6. Despite the negative connotation of the outcome this thesis, this work is another small step towards a better understanding of the exact relationship between cerebrovascular dysfunction and amyloid‑β deposition in AD and CAA patients. Ultimately, this will help in the design of highly needed novel therapies for AD and CAA. Show less
Ghaznawi, R.; Zwartbol, M.H.T.; Zuithoff, N.P.A.; Bresser, J. de; Hendrikse, J.; Geerlings, M.I.; UCC-SMART Study Grp 2020
Global cerebral hypoperfusion may be involved in the aetiology of brain atrophy; however, long-term longitudinal studies on this relationship are lacking. We examined whether reduced cerebral blood... Show moreGlobal cerebral hypoperfusion may be involved in the aetiology of brain atrophy; however, long-term longitudinal studies on this relationship are lacking. We examined whether reduced cerebral blood flow was associated with greater progression of brain atrophy. Data of 1165 patients (61 +/- 10 years) from the SMART-MR study, a prospective cohort study of patients with arterial disease, were used of whom 689 participated after 4 years and 297 again after 12 years. Attrition was substantial. Total brain volume and total cerebral blood flow were obtained from magnetic resonance imaging scans and expressed as brain parenchymal fraction (BPF) and parenchymal cerebral blood flow (pCBF). Mean decrease in BPF per year was 0.22% total intracranial volume (95% CI: -0.23 to -0.21). Mean decrease in pCBF per year was 0.24 ml/min per 100 ml brain volume (95% CI: -0.29 to -0.20). Using linear mixed models, lower pCBF at baseline was associated with a greater decrease in BPF over time (p = 0.01). Lower baseline BPF, however, was not associated with a greater decrease in pCBF (p = 0.43). These findings indicate that reduced cerebral blood flow is associated with greater progression of brain atrophy and provide further support for a role of cerebral blood flow in the process of neurodegeneration. Show less
Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently... Show moreIncreasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved. Show less
Petr, J.; Platzek, I.; Hofheinz, F.; Mutsaerts, H.J.M.M.; Asllani, I.; Osch, M.J.P. van; ... ; Hoff, J. van den 2018
The primary aim of the project “Go with the flow: the heart-brain axis” was to elucidate the interaction between heart and the brain, across the lifespan. This was done by integration of... Show moreThe primary aim of the project “Go with the flow: the heart-brain axis” was to elucidate the interaction between heart and the brain, across the lifespan. This was done by integration of physiological concepts into the MRI-environment and by monitoring brain perfusion at both the macrovascular level (using transcranial Doppler; TCD) and the tissue level (using arterial spin labeling MRI; ASL). This thesis focused on the comparison and validation of these two modalities used in this project. We found that high levels of end-tidal CO2, blood pressure and handgrip all influence the middle cerebral artery (MCA) diameter, challenging the long-held assumption of diameter constancy. Furthermore, we found that during rhythmic handgrip the flow velocity (TCD) increased, whereas no change in the MCA flow territory (ASL) could be observed. Therefore, whole-brain CBF-measurements by ASL do not support the claim that a change in flow velocity measured by TCD can be used as a proxy for regional CBF during rhythmic handgrip exercise. Finally, we found in simulations and in-vivo experiments only modest influence of the cardiac cycle on the end-of-labeling. Therefore, cardiac triggering at the start or the end of labeling has little benefit to pseudo-Continuous ASL signal stability. Show less
