Cerebral hemodynamics comparison using transcranial doppler ultrasound and 4D flow MRI.

Introduction: Age-related changes in cerebral hemodynamics are controversial and discrepancies may be due to experimental techniques. As such, the purpose of this study was to compare cerebral hemodynamics measurements of the middle cerebral artery (MCA) between transcranial Doppler ultrasound (TCD) and four-dimensional flow MRI (4D flow MRI). Methods: Twenty young (25 ± 3 years) and 19 older (62 ± 6 years) participants underwent two randomized study visits to evaluate hemodynamics at baseline (normocapnia) and in response to stepped hypercapnia (4% CO2, and 6% CO2) using TCD and 4D flow MRI. Cerebral hemodynamic measures included MCA velocity, MCA flow, cerebral pulsatility index (PI) and cerebrovascular reactivity to hypercapnia. MCA flow was only assessed using 4D flow MRI. Results: MCA velocity between the TCD and 4D flow MRI methods was positively correlated across the normocapnia and hypercapnia conditions (r = 0.262; p = 0.004). Additionally, cerebral PI was significantly correlated between TCD and 4D flow MRI across the conditions (r = 0.236; p = 0.010). However, there was no significant association between MCA velocity using TCD and MCA flow using 4D flow MRI across the conditions (r = 0.079; p = 0.397). When age-associated differences in cerebrovascular reactivity using conductance were compared using both methodologies, cerebrovascular reactivity was greater in young adults compared to older adults when using 4D flow MRI (2.11 ± 1.68 mL/min/mmHg/mmHg vs. 0.78 ± 1.68 mL/min/mmHg/mmHg; p = 0.019), but not with TCD (0.88 ± 1.01 cm/s/mmHg/mmHg vs. 0.68 ± 0.94 cm/s/mmHg/mmHg; p = 0.513). Conclusion: Our results demonstrated good agreement between the methods at measuring MCA velocity during normocapnia and in response to hypercapnia, but MCA velocity and MCA flow were not related. In addition, measurements using 4D flow MRI revealed effects of aging on cerebral hemodynamics that were not apparent using TCD.

Focused Abbreviated Survey MRI Protocols for Brain and Spine Imaging.

There has been extensive growth in both the technical development and the clinical applications of MRI, establishing this modality as one of the most powerful diagnostic imaging tools. However, long examination and image interpretation times still limit the application of MRI, especially in emergent clinical settings. Rapid and abbreviated MRI protocols have been developed as alternatives to standard MRI, with reduced imaging times, and in some cases limited numbers of sequences, to more efficiently answer specific clinical questions. A group of rapid MRI protocols used at the authors' institution, referred to as FAST (focused abbreviated survey techniques), are designed to include or exclude emergent or urgent conditions or screen for specific entities. These FAST protocols provide adequate diagnostic image quality with use of accelerated approaches to produce imaging studies faster than traditional methods. FAST protocols have become critical diagnostic screening tools at the authors' institution, allowing confident and efficient confirmation or exclusion of actionable findings. The techniques commonly used to reduce imaging times, the imaging protocols used at the authors' institution, and future directions in FAST imaging are reviewed to provide a practical and comprehensive overview of FAST MRI for practicing neuroradiologists. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Normative Cerebral Hemodynamics in Middle-aged and Older Adults Using 4D Flow MRI: Initial Analysis of Vascular Aging.

Background Characterizing cerebrovascular hemodynamics in older adults is important for identifying disease and understanding normal neurovascular aging. Four-dimensional (4D) flow MRI allows for a comprehensive assessment of cerebral hemodynamics in a single acquisition. Purpose To establish reference intracranial blood flow and pulsatility index values in a large cross-sectional sample of middle-aged (45-65 years) and older (>65 years) adults and characterize the effect of age and sex on blood flow and pulsatility. Materials and Methods In this retrospective study, patients aged 45-93 years (cognitively unimpaired) underwent cranial 4D flow MRI between March 2010 and March 2020. Blood flow rates and pulsatility indexes from 13 major arteries and four venous sinuses and total cerebral blood flow were collected. Intraobserver and interobserver reproducibility of flow and pulsatility measures was assessed in 30 patients. Descriptive statistics (mean ± SD) of blood flow and pulsatility were tabulated for the entire group and by age and sex. Multiple linear regression and linear mixed-effects models were used to assess the effect of age and sex on total cerebral blood flow and vessel-specific flow and pulsatility, respectively. Results There were 759 patients (mean age, 65 years ± 8 [SD]; 506 female patients) analyzed. For intra- and interobserver reproducibility, median intraclass correlation coefficients were greater than 0.90 for flow and pulsatility measures across all vessels. Regression coefficients ß ± standard error from multiple linear regression showed a 4 mL/min decrease in total cerebral blood flow each year (age ß = -3.94 mL/min per year ± 0.44; P < .001). Mixed effects showed a 1 mL/min average annual decrease in blood flow (age ß = -0.95 mL/min per year ± 0.16; P < .001) and 0.01 arbitrary unit (au) average annual increase in pulsatility over all vessels (age ß = 0.011 au per year ± 0.001; P < .001). No evidence of sex differences was observed for flow (ß = -1.60 mL/min per male patient ± 1.77; P = .37), but pulsatility was higher in female patients (sex ß = -0.018 au per male patient ± 0.008; P = .02). Conclusion Normal reference values for blood flow and pulsatility obtained using four-dimensional flow MRI showed correlations with age. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Steinman in this issue.

The Impact of Aging on the Association Between Aortic Stiffness and Cerebral Pulsatility Index.

The central arteries dampen the pulsatile forces from myocardial contraction, limiting the pulsatility that reaches the cerebral vasculature, although there are limited data on this relationship with aging in humans. The purpose of this study was to determine the association between aortic stiffness and cerebral artery pulsatility index in young and older adults. We hypothesized that cerebral pulsatility index would be associated with aortic stiffness in older adults, but not in young adults. We also hypothesized that both age and aortic stiffness would be significant predictors for cerebral pulsatility index. This study included 23 healthy older adults (aged 62 ± 6 years) and 33 healthy young adults (aged 25 ± 4 years). Aortic stiffness was measured using carotid-femoral pulse wave velocity (cfPWV), while cerebral artery pulsatility index in the internal carotid arteries (ICAs), middle cerebral arteries (MCAs), and basilar artery were assessed using 4D Flow MRI. Cerebral pulsatility index was calculated as (maximum flow - minimum flow) / mean flow. In the combined age group, there was a positive association between cfPWV and cerebral pulsatility index in the ICAs (r = 0.487; p < 0.001), MCAs (r = 0.393; p = 0.003), and basilar artery (r = 0.576; p < 0.001). In young adults, there were no associations between cfPWV and cerebral pulsatility index in any of the arteries of interest (ICAs: r = 0.253; p = 0.156, MCAs: r = -0.059; p = 0.743, basilar artery r = 0.171; p = 0.344). In contrast, in older adults there was a positive association between cfPWV and cerebral pulsatility index in the MCAs (r = 0.437; p = 0.037) and basilar artery (r = 0.500; p = 0.015). However, the relationship between cfPWV and cerebral pulsatility index in the ICAs of the older adults did not reach the threshold for significance (r = 0.375; p = 0.078). In conclusion, age and aortic stiffness are significant predictors of cerebral artery pulsatility index in healthy adults. This study highlights the importance of targeting aortic stiffness in our increasingly aging population to reduce the burden of age-related changes in cerebral hemodynamics.

Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer's disease.

Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric-fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO-is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer's disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.

Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study.

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40-89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13-8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (ß=-1.43), hippocampus (-1.25), superior frontal gyrus (-1.70), middle frontal gyrus (-1.99), posterior cingulate (-2.46), and precuneus (-2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.

Neurodegeneration, Alzheimer's disease biomarkers, and longitudinal verbal learning and memory performance in late middle age.

This study examined the effect of neurodegeneration, and its interaction with Alzheimer's disease (AD) cerebrospinal fluid biomarkers, on longitudinal verbal learning and memory performance in cognitively unimpaired (CU) late middle-aged adults. Three hundred and forty-two CU adults (cognitive baseline mean age = 58.4), with cerebrospinal fluid and structural MRI, completed 2-10 (median = 5) cognitive assessments. Learning and memory were assessed using the Rey Auditory Verbal Learning Test (RAVLT). We used sequential comparison of nested linear mixed effects models to analyze the data. Model selection preserved a significant ptau181/Aß42 × global atrophy × age interaction; individuals with less global atrophy and lower ptau181/Aß42 levels had less learning and delayed recall decline than individuals with more global atrophy and/or higher levels of ptau181/Aß42. The hippocampal volume × age × ptau181/Aß42 interaction was not significant. Findings suggest that in a sample of CU late middle-aged adults, individuals with AD biomarkers, global atrophy, or both evidence greater verbal learning and memory decline than individuals without either risk factor.

Assessment of vascular stiffness in the internal carotid artery proximal to the carotid canal in Alzheimer's disease using pulse wave velocity from low rank reconstructed 4D flow MRI.

Clinical evidence shows vascular factors may co-occur and complicate the expression of Alzheimer's disease (AD); yet, the pathologic mechanisms and involvement of different compartments of the vascular network are not well understood. Diseases such as arteriosclerosis diminish vascular compliance and will lead to arterial stiffness, a well-established risk factor for cardiovascular morbidity. Arterial stiffness can be assessed using pulse wave velocity (PWV); however, this is usually done from carotid-to-femoral artery ratios. To probe the brain vasculature, intracranial PWV measures would be ideal. In this study, high temporal resolution 4D flow MRI was used to assess transcranial PWV in 160 subjects including AD, mild cognitive impairment (MCI), healthy controls, and healthy subjects with apolipoprotein ɛ4 positivity (APOE4+) and parental history of AD dementia (FH+). High temporal resolution imaging was achieved by high temporal binning of retrospectively gated data using a local-low rank approach. Significantly higher transcranial PWV in AD dementia and MCI subjects was found when compared to old-age-matched controls (AD vs. old-age-matched controls: P <0.001, AD vs. MCI: P = 0.029, MCI vs. old-age-matched controls P = 0.013). Furthermore, vascular changes were found in clinically healthy middle-age adults with APOE4+ and FH+ indicating significantly higher transcranial PWV compared to controls (P <0.001).

Cerebrovascular stiffness and flow dynamics in the presence of amyloid and tau biomarkers.

INTRODUCTION: This work investigated the relationship between cerebrovascular disease (CVD) markers and Alzheimer's disease (AD) biomarkers of amyloid beta deposition, and neurofibrillary tau tangles in subjects spanning the AD clinical spectrum. METHODS: A total of 136 subjects participated in this study. Four groups were established based on AD biomarker positivity from positron emission tomography (amyloid [A] and tau [T]) and clinical diagnosis (cognitively normal [CN] and impaired [IM]). CVD markers were derived from structural and quantitative magnetic resonance imaging data. RESULTS: Transcapillary pulse wave delay was significantly longer in controls compared to AT biomarker-confirmed groups (A+/T-/CN P < .001, A+/T+/CN P < .001, A+/T+/IM P = .003). Intracranial low-frequency oscillations were diminished in AT biomarker-confirmed groups both CN and impaired (A+/T-/CN P = .039, A+/T+/CN P = .007, A+/T+/IM P = .011). A significantly higher presence of microhemorrhages was measured in A+/T+/CN compared to controls (P = .006). DISCUSSION: Cerebrovascular markers indicate increased vessel stiffness and reduced vasomotion in AT biomarker-positive subjects during preclinical AD.

Vertebral artery hypoplasia influences age-related differences in blood flow of the large intracranial arteries.

Our purpose was to compare cerebral blood flow in the large intracranial vessels between healthy adults with (VAH+) and without (No VAH) vertebral artery hypoplasia. We also evaluated age-related differences in regional blood flow through the large cerebral arteries. Healthy young (n = 20; age = 25 ±â€¯3 years) and older adults (n = 19; age = 61 ±â€¯5 years) underwent 4D flow MRI scans to evaluate blood flow in the internal carotid arteries (ICA) and basilar artery (BA). VAH was determined retrospectively from 4D flow MRI using both structural (vessel diameter ≤ 2 mm) and flow criteria (flow ≤ 50 mL/min). We identified 5 young and 5 older adults with unilateral VAH (prevalence = 26%). ICA flow was lower in the VAH+ group compared with the No VAH group (367 ±â€¯75 mL/min vs. 432 ±â€¯92 mL/min, respectively; p < 0.05). There was no difference in BA flow between VAH+ and No VAH (110 ±â€¯20 mL/min vs. 126 ±â€¯40 mL/min, respectively; p = 0.24). When comparing age-related differences in blood flow in the No VAH group, older adults demonstrated lower BA flow compared with young adults (111 ±â€¯38 mL/min vs. 140 ±â€¯38 mL/min, respectively; p < 0.05) but not ICA flow (428 ±â€¯89 mL/min vs. 436 ±â€¯98 mL/min, respectively; p = 0.82). In contrast, in the VAH+ group, older adults had lower ICA flow compared with young adults (312 ±â€¯65 mL/min vs. 421 ±â€¯35 mL/min, respectively; p < 0.01), but not BA flow (104 ±â€¯16 mL/min vs. 117 ±â€¯23 mL/min, respectively; p = 0.32). Our results suggest that the presence of VAH is associated with lower ICA blood flow. Furthermore, VAH may contribute to the variability in the age-related differences in cerebral blood flow in healthy adults.

Intracranial vascular flow oscillations in Alzheimer's disease from 4D flow MRI.

Recent modeling and experimental evidence suggests clearance of soluble metabolites from the brain can be driven by low frequency flow oscillations (LFOs) through the intramural periarterial drainage (IPAD) pathway. This study investigates the use of 4D flow MRI to derive LFOs from arterial and venous measures of blood flow. 3D radial 4D flow MRI data were acquired on a 3.0 T scanner and reconstructed using a low-rank constraint to produce time resolved measurements of blood flow. Physical phantom experiments were performed to validate the time resolved 4D flow against a standard 2D phase contrast (PC) approach. To evaluate the ability of 4D flow to distinguish physiologic flow changes from noise, healthy volunteers were scanned during a breath-hold (BH) maneuver and compared against 2D PC measures. Finally, flow measures were performed in intracranial arteries and veins of 112 participants including subjects diagnosed with Alzheimer's disease (AD) clinical syndrome (n = 23), and healthy controls (n = 89) on whom apolipoprotein ɛ4 positivity (APOE4+) and parental history of AD dementia (FH+) was known. To assess LFOs, flow range, standard deviation, demeaned temporal flow changes, and power spectral density were quantified from the time series. Group differences were assessed using ANOVA followed by Tukey-Kramer method for pairwise comparison for adjusted means (P < 0.05). Significantly lower LFOs as measured from flow variation range and standard deviations were observed in the arteries of AD subjects when compared to age-matched controls (P = 0.005, P = 0.011). Results suggest altered vascular function in AD subjects. 4D flow based spontaneous LFO measures might hold potential for longitudinal studies aimed at predicting cognitive trajectories in AD and study disease mechanisms.

Fitness, independent of physical activity is associated with cerebral blood flow in adults at risk for Alzheimer's disease.

Patterns of decreased resting cerebral blood flow (CBF) within the inferior temporal gyri, angular gyri, and posterior cingulate are a feature of aging and Alzheimer's disease (AD) and have shown to be predictive of cognitive decline among older adults. Fitness and physical activity are both associated with many indices of brain health and may positively influence CBF, however, the majority of research to date has examined these measures in isolation, leaving the potential independent associations unknown. The purpose of this study was to determine the unique contributions of fitness and physical activity when predicting CBF in cognitively healthy adults at risk for AD. One hundred participants (63% female) from the Wisconsin Registry for Alzheimer's Prevention underwent a maximal exercise test, physical activity monitoring, and a 3-D arterial spin labeling magnetic resonance imaging scan. For the entire sample, fitness was significantly associated with CBF while accounting for physical activity, age, gender, APOE ε4, family history of AD, education, and handedness (p = .026). Further, fitness explained significantly more variance than the combined effect of the covariates on CBF (R2 change = .059; p = .047). These results appear to be gender dependent, our data suggest fitness level, independent of physical activity, is associated with greater CBF in regions that are known to decline with age and AD for female (p = .011), but not male participants.

Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age.

This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified groups in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer's Prevention. One hundred and sixty-seven initially unimpaired individuals (baseline age 59 ± 6 years; 115 females) were stratified by elevated amyloid-ß and tau status based on 11C-Pittsburgh compound B (PiB) and 18F-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differed between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between 18F-MK-6240, 11C-PiB, and age. A significant group × age interaction was observed with post hoc comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust against various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did not differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry. Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and 18F-MK-6240 in tangle-associated regions, which were negligible after adjusting for 11C-PiB. Strong associations, particularly in entorhinal cortex, hippocampus and amygdala, were observed between 18F-MK-6240 and global 11C-PiB in regions associated with Braak neurofibrillary tangle stages I-VI. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer's disease during late middle-age. Within the Alzheimer's disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. 18F-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer's disease.

Age-Related Reductions in Cerebrovascular Reactivity Using 4D Flow MRI.

Cerebrovascular reactivity (CVR), is important for determining future risk of cerebrovascular disease. It is unclear if primary aging is associated with reductions in CVR because previous studies often include participants with vascular risk factors. Additionally, the inconsistency in the literature may be due to the inherent difficulty in quantifying intracranial cerebral blood flow and CVR. To address these limitations, we determined the effect of age on CVR in the large intracranial vessels in adults with low vascular risk using state-of-the-art MRI techniques. We also determined if the effect of age on CVR was sex-specific. Young (n = 20; 25 ± 3 years) and older (n = 19; 61 ± 5 years) healthy, physically active adults participated in the study. CVR was measured in response to hypercapnia using 4D flow MRI, which allows for simultaneous angiographic and quantitative blood flow measurements in the intracranial arteries. Older adults had lower global CVR and CVR in multiple intracranial arteries [right and left internal carotid arteries (ICA), right and left middle cerebral arteries (MCA), and basilar artery (BA)] compared with young adults (p < 0.05 for all). In addition, the MCA dilated significantly in response to hypercapnia in young (p < 0.05), but not older adults. Young men demonstrated higher global CVR and CVR in multiple intracranial arteries (ICAs, MCAs, and BA) compared with young women and older men (p < 0.05 for both); however, CVR did not differ between young women and older women. Our results demonstrate that, using 4D flow MRI, primary aging is associated with lower CVR in adults with low vascular risk. In addition, the effect of age on CVR may be driven by men. The 4D flow MRI technique may provide a promising new alternative to measure cerebrovascular physiology without the limitations of commonly used techniques. Future studies could utilize this MRI technique to examine interventions to maintain CVR with advancing age. This study was registered under clinicaltrials.gov # NCT02840851.

Comparison of different MRI-based morphometric estimates for defining neurodegeneration across the Alzheimer's disease continuum.

BACKGROUND: Several neurodegeneration (N) metrics using structural MRI are used for the purpose of Alzheimer's disease (AD)-related staging, including hippocampal volume, global atrophy, and an "AD signature" composite consisting of thickness or volumetric estimates derived from regions impacted early in AD. This study sought to determine if less user-intensive estimates of global atrophy and hippocampal volume were equivalent to a thickness-based AD signature from FreeSurfer for defining N across the AD continuum (i.e., individuals who are amyloid-positive (A+)). METHODS: Cognitively unimpaired (CU) late middle-aged and older adults, as well as A+ mild cognitive impairment (MCI) and A+ AD dementia individuals, with available CSF and structural MRI scan <1.5 years apart, were selected for the study (n = 325, mean age = 62). First, in a subsample of A+ AD dementia and matched biomarker-negative (i.e., A- and tau tangle pathology (T)-) CU controls (n = 40), we examined ROC characteristics and identified N cut-offs using Youden's J for neurofilament light chain protein (NfL) and each of three MRI-based measures: a thickness-based AD signature from FreeSurfer, hippocampal volume (using FIRST), and a simple estimate of global atrophy (the ratio of intracranial CSF segmented volume to brain tissue volume, using SPM12). Based on the results from the ROC analyses, we then examined the concordance between NfL N positivity and N positivity for each MRI-based metric using Cohen's Kappa in the remaining subsample of 285 individuals. Finally, in the full sample (n = 325), we examined the relationship between the four measures of N and group membership across the AD continuum using Kruskal-Wallis tests and Cliff's deltas. RESULTS: The three MRI-based metrics and CSF NfL similarly discriminated between the A-T- CU (n = 20) and A+ AD (n = 20) groups (AUCs ≥0.885; ps < 0.001). Using the cut-off values derived from the ROCs to define N positivity, there was weak concordance between NfL and all three MRI-derived metrics of N in the subsample of 285 individuals (Cohen's Kappas ≤0.429). Finally, the three MRI-based measures of N and CSF NfL showed similar associations with AD continuum group (i.e., Kruskal-Wallis ps < 0.001), with relatively larger effect sizes noted when comparing the A-T- CU to the A+ MCI (Cliff's deltas ≥0.741) and A+ AD groups (Cliff's deltas ≥0.810) than to the A+T- CU (Cliff's deltas = 0.112-0.298) and A + T+ CU groups (Cliff's deltas = 0.212-0.731). CONCLUSIONS: These findings suggest that the three MRI-based morphometric estimates and CSF NfL similarly differentiate individuals across the AD continuum on N status. In many applications, a simple estimate of global atrophy may be preferred as an MRI marker of N across the AD continuum given its methodological robustness and ease of calculation when compared to hippocampal volume or a cortical thickness AD signature.

Standards of Practice in Acute Ischemic Stroke Intervention International Recommendations.

After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.