Magnetic resonance angiography of collateral compensation in asymptomatic and symptomatic internal carotid artery stenosis

AbstractObjective: In patients with stenosis of the internal carotid artery (ICA), the presence of collateral circulatory pathways may be crucial to maintain cerebral perfusion pressure, metabolism, and function. The purpose of the present study was to determine whether patients with asymptomatic stenosis of the ICA have a better collateral ability of the circle of Willis when compared with patients with symptomatic ICA stenosis. Method: Magnetic resonance angiography consisting of the circle of Willis was performed in 19 patients with severe asymptomatic ICA stenosis and in 21 patients with severe symptomatic ICA stenosis prior to carotid endarterectomy and in 53 control subjects. Between group comparisons were made for function (directional flow) and anatomy (diameter). Results: In patients with asymptomatic ICA stenosis, the prevalence of collateral flow via the anterior communicating artery was significantly increased (37%, 7 of 19) compared with symptomatic patients (10%, 2 of 21) and control subjects (0%; P < .001). Patients with asymptomatic ICA stenosis demonstrated the largest mean diameter of the anterior communicating artery (1.33 ± 0.18 mm) compared with patients with symptomatic ICA stenosis (1.22 ± 0.18 mm) and control subjects (1.06 ± 0.10 mm, P < .05). No differences in collateral flow pattern or diameter were found for the posterior communicating artery between the groups. Conclusions: The present cross-sectional study demonstrates the importance of an adequate hemodynamic compensation via the circle of Willis in patients with ICA stenosis. Whether differences in collateral compensation can be used to select patients for CEA has yet to be determined. (J Vasc Surg 2002;36:799-805.

Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion

Abstract The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose was a 2.2% decrease. Administration of water did not affect the hypothalamic BOLD responses. Intranasal insulin did not change circulating glucose and insulin levels. Still, circulating glucose levels showed a significant dampening effect on the BOLD response and insulin levels a significant strengthening effect. Our data provide proof of concept for future experiments testing the potential of intranasal application of insulin to ameliorate defective homeostatic control in patients with type 2 diabetes

Effect of intranasally administered insulin on cerebral blood flow and perfusion:a randomized experiment in young and older adults

Pathophysiology, epidemiology and therapy of agein

Cognitive function in dementia-free subjects and survival in old Age: The PROSPER study

Impairment in domain-specific cognitive function is associated with the increased risk of mortality. We prospectively evaluated the association of executive function and memory with the risk of long-term mortality in dementia-free older subjects. Moreover, we investigated the role of structural brain abnormalities in this association. We included 547 dementia-free participants (mean age 78years, 56.5% male) from the nested magnetic resonance imaging sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were used to model 10-year risk of all-cause, cardiovascular and non-cardiovascular mortality in relation to performance in executive function and memory. Moreover, we evaluated the role of total brain parenchymal volume, cerebral blood flow, white matter hyperintensity and the presence of microbleeds and infarcts in the link between cognitive function and mortality. In the multivariable model, lower performance in executive function was associated with greater risk of all-cause (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.31-1.70), cardiovascular (HR 1.69, 95%CI 1.36-2.11) and non-cardiovascular (HR 1.36, 95%CI 1.15-1.62) mortality. Similarly, poorer performance in memory tests associated with higher risk of all-cause (HR 1.47, 95%CI 1.29-1.68), cardiovascular (HR 1.45, 95%CI 1.15-1.83) and non-cardiovascular (HR 1.49, 95%CI 1.27-1.76) mortality. The associations were similar in subjects with various levels of brain structural abnormalities and cerebral blood flow (all p for interaction &gt;0.05). Poorer performance in both executive function and memory tests associates with all-cause, cardiovascular and non-cardiovascular mortality in elderly individuals. This association is independent of cardiovascular risk factors and diseases, brain structural abnormalities and cerebral blood flow

Combining anatomical, diffusion, and resting state functional magnetic resonance imaging for individual classification of mild and moderate Alzheimer's disease

AbstractMagnetic resonance imaging (MRI) is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD), and can therefore be used to help in diagnosing the disease. Improving classification of AD patients based on MRI scans might help to identify AD earlier in the disease's progress, which may be key in developing treatments for AD. In this study we used an elastic net classifier based on several measures derived from the MRI scans of mild to moderate AD patients (N=77) from the prospective registry on dementia study and controls (N=173) from the Austrian Stroke Prevention Family Study. We based our classification on measures from anatomical MRI, diffusion weighted MRI and resting state functional MRI. Our unimodal classification performance ranged from an area under the curve (AUC) of 0.760 (full correlations between functional networks) to 0.909 (grey matter density). When combining measures from multiple modalities in a stepwise manner, the classification performance improved to an AUC of 0.952. This optimal combination consisted of grey matter density, white matter density, fractional anisotropy, mean diffusivity, and sparse partial correlations between functional networks. Classification performance for mild AD as well as moderate AD also improved when using this multimodal combination. We conclude that different MRI modalities provide complementary information for classifying AD. Moreover, combining multiple modalities can substantially improve classification performance over unimodal classification

Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer's disease

Introduction: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. Early differentiation between both types of dementia may be challenging due to heterogeneity and overlap of symptoms. Here, we apply resting state functional magnetic resonance imaging (fMRI) to study functional brain connectivity differences between AD and bvFTD. Methods: We used resting state fMRI data of 31 AD patients, 25 bvFTD patients, and 29 controls from two centers specialized in dementia. We studied functional connectivity throughout the entire brain, applying two different analysis techniques, studying network-to-region and region-to-region connectivity. A general linear model approach was used to study group differences, while controlling for physiological noise, age, gender, study center, and regional gray matter volume. Results: Given gray matter differences, we observed decreased network-to-region connectivity in bvFTD between (a) lateral visual cortical network and lateral occipital and cuneal cortex, and (b) auditory system network and angular gyrus. In AD, we found decreased network-to-region connectivity between the dorsal visual stream network and lateral occipital and parietal opercular cortex. Region-to-region connectivity was decreased in bvFTD between superior temporal gyrus and cuneal, supracalcarine, intracalcarine cortex, and lingual gyrus. Conclusion: We showed that the pathophysiology

Multimodal MRI of grey matter, white matter, and functional connectivity in cognitively healthy mutation carriers at risk for frontotemporal dementia and Alzheimer's disease

Background: Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are associated with divergent differences in grey matter volume, white matter diffusion, and functional connectivity. However, it is unknown at what disease stage these differences emerge. Here, we investigate whether divergent differences in grey matter volume, white matter diffusion, and functional connectivity are already apparent between cognitively healthy carriers of pathogenic FTD mutations, and cognitively healthy carriers at increased AD risk. Methods: We acquired multimodal magnetic resonance imaging (MRI) brain scans in cognitively healthy subjects with (n=39) and without (n=36) microtubule-associated protein Tau (MAPT) or progranulin (GRN) mutations, and with (n=37) and without (n=38) apolipoprotein E ϵ4 (APOE4) allele. We evaluated grey matter volume using voxel-based morphometry, white matter diffusion using tract-based spatial statistics (TBSS), and region-to-network functional connectivity using dual regression in the default mode network and salience network. We tested for differences between the respective carriers and controls, as well as for divergence of those differences. For the divergence contrast, we additionally performed region-of-interest TBSS analyses in known areas o

Selective Involvement of the Amygdala in Systemic Lupus Erythematosus

BACKGROUND: Antibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE). The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE. METHODS AND FINDINGS: We analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE), 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI). In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC) was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 × 10(−6) mm(2)/s; p = 0.006 and 949 × 10(−6) mm(2)/s; p = 0.019, respectively) was lower than in healthy control participants (1152 × 10(−6) mm(2)/s). Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 × 10(−6) mm(2)/s) was lower (p = 0.029) than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 × 10(−6) mm(2)/s) and also lower (p = 0.001) than in healthy control participants. CONCLUSIONS: This is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies

Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study

We investigated the ability of cortical and subcortical gray matter (GM) atrophy in combination with white matter (WM) integrity to distinguish behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA) and higher mean (MD), axial (L1) and radial diffusivity (L23) values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97-100% of controls, 81-100% of AD and 67-75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD

Magnetization transfer imaging in ‘premanifest’ Huntington’s disease

To investigate whether magnetization transfer imaging (MTI) is a useful detector of diffuse brain abnormalities in ‘premanifest’ carriers of the Huntington’s disease (HD) gene mutation. Furthermore we examined the relations between MTI, clinical measures and CAG repeat length. Sixteen premanifest carriers of the HD gene without motor manifestation and 14 non-carriers underwent a clinical evaluation and a MRI scan. MTI analysis of whole brain, grey matter and white matter was performed producing magnetization transfer ratio (MTR) histograms. A lower peak height of the grey matter MTR histogram in carriers was significantly associated with more UHDRS motor abnormalities. Furthermore, a lower peak height of the whole brain, grey and white matter was strongly associated with a longer CAG repeat length. MTI measures themselves did not differ significantly between carriers and non-carriers. In premanifest HD mutation carriers, a lower MTR peak height, reflecting worse histological brain composition, was related to subtle motor abnormalities and higher CAG repeat length. Although we could not detect altered MTI characteristics in carriers of the HD gene mutation without clinical manifestations, we did provide evidence that the MTR peak height might reflect genetic and subclinical disease burden and may be of value in monitoring further disease progression and provide insight in clinical heterogeneity