Assessment Of Brain Atrophy Research Articles

MRI biomarkers for Alzheimer's disease: the impact of functional connectivity in the default mode network and structural connectivity between lobes on diagnostic accuracy

BackgroundAt present, clinical use of MRI in Alzheimer's disease (AD) is mostly focused on the assessment of brain atrophy, namely in the hippocampal region. Despite this, multiple biomarkers reflecting structural and functional brain connectivity changes have shown promising results in the assessment of AD. To help identify the most relevant ones that may stand a chance of being used in clinical practice, we compared multiple biomarker in terms of their value to discriminate AD from healthy controls and analyzed their age dependency. Methods20 AD patients and 20 matched controls underwent MRI-scanning (3T GE), including T1-weighted, diffusion-MRI, and resting-state-fMRI (rsfMRI). Whole brain, white matter, gray matter, cortical gray matter and hippocampi volumes were measured using icobrain. rsfMRI between regions of the default-mode-network (DMN) was assessed using group independent-component-analysis. Median diffusivity and kurtosis were determined in gray and white-matter. DTI data was used to evaluate pairwise structural connectivity between lobar regions and the hippocampi.Logistic-Regression and Random-Forest models were trained to classify AD-status based on, respectively different isolated features and age, and feature-groups combined with age. ResultsHippocampal features, features reflecting the functional connectivity between the medial-Pre-Frontal-Cortex (mPFC) and the posterior regions of the DMN, and structural interhemispheric frontal connectivity showed the strongest differences between AD-patients and controls. Structural interhemispheric parietal connectivity, structural connectivity between the parietal lobe and hippocampus in the right hemisphere, and mPFC-DMN-features, showed only an association with AD-status (p < 0.05) but not with age. Hippocampi volumes showed an association both with age and AD-status (p < 0.05).Smallest-hippocampus-volume was the most discriminative feature. The best performance (accuracy:0.74, sensitivity:0.74, specificity:0.74) was obtained with an RF-model combining the best feature from each feature-group (smallest hippocampus volume, WM volume, median GM MD, lTPJ-mPFC connectivity and structural interhemispheric frontal connectivity) and age. ConclusionsBrain connectivity changes caused by AD are reflected in multiple MRI-biomarkers. Decline in both the functional DMN-connectivity and the parietal interhemispheric structural connectivity may assist sepparating healthy-aging driven changes from AD, complementing hippocampal volumes which are affected by both aging and AD.

The impact of brain atrophy on the outcomes of mechanical thrombectomy.

Pre-existing brain atrophy may affect the outcomes of patients treated with mechanical thrombectomy (MT) for large-vessel-occlusion because it is an indicator of low brain reserve. We performed a systematic literature review to assess the impact of brain atrophy on MT-related clinical outcomes. We conducted a systematic search of PubMed, MEDLINE, EMBASE, and Cochrane Library databases from inception to March 2021 using keywords with Boolean operators("brain atrophy"; "atrophy"; "white matter"; and "thrombectomy"). Articles published in English that evaluated the impact of pre-existing brain atrophy on outcomes of MT-treated acute ischemic stroke were eligible for inclusion. Four articles were included. Brain atrophy index was a predictor of mortality (odds ratio [OR]:1.81-1.87, 95% confidence interval [CI]:1.16-2.93) after adjustments for age and white matter lesions. Global cortical atrophy scale was an independent predictor of futile recanalization (OR 1.15, 95% CI 1.08-1.22) in multivariate-adjusted logistic regression. Automated measurement of CSF identified increasing volumes associated with reduced 3-month functional independence and higher modified Rankin scale scores. STandards for ReportIng Vascular changes on Neuroimaging criteria for brain atrophy were associated with unfavorable outcome in ordinal-shift analysis (OR 2.72, 95% CI 1.25-5.91). The few studies available highlight heterogeneity of neuroimaging methodologies for assessing brain atrophy and difficulty addressing the multiple confounders involved in clinical outcomes. More consistent, accurate investigation is needed before proposing brain atrophy as a possible parameter to improve patient selection for MT. Brain atrophy is associated with many of the clinical confounders frequently present in patients with acute ischemic stroke. Heterogeneity in classification methodologies for brain atrophy and complexity analyzing multiple clinical confounders make it difficult to assess the true impact of this radiological finding on MT-related outcomes.

Mitochondrial complex I abnormalities underlie neurodegeneration and cognitive decline in Alzheimer's disease.

Abnormal mitochondrial metabolism has been described in the Alzheimer's disease (AD) brain. However, the relationship between AD pathophysiology and key mitochondrial processes remains elusive. The purpose of this study was to investigate whether mitochondrial complex I dysfunction is associated with amyloid aggregation or glucose metabolism and brain atrophy in patients with mild AD using positron emission tomography (PET). Amyloid- and tau-positive symptomatic AD patients with clinical dementia rating 0.5 or 1 (N=30; mean age±standard deviation: 71.8±7.6years) underwent magnetic resonance imaging and PET scans with [18 F]2-tert-butyl-4-chloro-5-2H-pyridazin-3-one (BCPP-EF), [11 C]Pittsburgh Compound-B (PiB) and [18 F]fluorodeoxyglucose (FDG) to assess brain atrophy, mitochondrial complex I dysfunction, amyloid deposition, and glucose metabolism, respectively. Local cortical associations among these biomarkers and gray matter volume were evaluated with voxel-based regressions models. [18 F]BCPP-EF standardized uptake value ratio (SUVR) was positively correlated with [18 F]FDG SUVR in the widespread brain area, while its associations with gray matter volume were restricted to the parahippocampal gyrus. Reductions in [18 F]BCPP-EF SUVR were associated with domain-specific cognitive performance. We did not observe regional associations between mitochondrial dysfunction and amyloid burden. In symptomatic cases, although mitochondrial complex I reduction is linked to a wide range of downstream neurodegenerative processes such as hypometabolism, atrophy, and cognitive decline, a link to amyloid was not observable. The data presented here support [18 F]BCPP-EF as an excellent imaging tool to investigate mitochondrial dysfunction in AD.

Brain CT can predict low lean mass in the elderly with cognitive impairment: a community-dwelling study

BackgroundThe coexistence of sarcopenia and dementia in aging populations is not uncommon, and they may share common risk factors and pathophysiological pathways. This study aimed to evaluate the relationship between brain atrophy and low lean mass in the elderly with impaired cognitive function.MethodsThis cross-sectional study included 168 elderly patients who visited the multi-disciplinary dementia outpatient clinic at Kaohsiung Chang Gung Memorial Hospital for memory issues, between 2017 and 2019. The body composition was assessed by dual energy X-ray absorptiometry (DEXA) and CT based skeletal muscle index including L3 skeletal muscle index (L3SMI) and masseter muscle mass index (MSMI). The brain atrophy assessment was measured by CT based visual rating scale. Possible predictors of low lean mass in the elderly with cognitive impairement were identified by binary logistic regression. ROC curves were generated from binary logistic regression.ResultsAmong the 81 participants, 43 (53%) remained at a normal appendicular skeletal muscle index (ASMI), whereas 38 (47%) showed low ASMI. Compared with the normal ASMI group, subjects with low ASMI exhibited significantly lower BMI, L3SMI, and MSMI (all p < 0.05), and showed significant brain atrophy as assessed by visual rating scale (p < 0.001). The accuracy of predictive models for low ASMI in the elderly with cognitive impairment were 0.875, (Area under curve (AUC) = 0.926, 95% confidence interval [CI] 0.844–0.972) in model 1 (combination of BMI, GCA and L3SMI) and 0.885, (Area under curve (AUC) = 0.931, [CI] 0.857–0.979) in model 2 (combination of BMI, GCA and MSMI).ConclusionsGlobal cortical atrophy and body mass index combined with either L3 skeletal muscle index or masseter skeletal muscle index can predict low lean mass in the elderly with cognitive impairment.

Hippocampo-Horn Percentage and Parietal Atrophy Score for Easy Visual Assessment of Brain Atrophy on Magnetic Resonance Imaging in Early- and Late-Onset Alzheimer’s Disease

Background:Magnetic resonance imaging (MRI) visual scales of brain atrophy are important for differential diagnosis of dementias in routine clinical practice. Atrophy patterns in early- and late-onset Alzheimer’s disease (AD) can be different according to some studies.Objective:Our goal was to assess brain atrophy patterns in early- and late-onset AD using our recently developed simple MRI visual scales and evaluate their reliability.Methods:We used Hippocampo-horn percentage (Hip-hop) and Parietal Atrophy Score (PAS) to compare mediotemporal and parietal atrophy on brain MRI among 4 groups: 26 patients with early-onset AD, 21 younger cognitively normal persons, 32 patients with late-onset AD, and 36 older cognitively normal persons. Two raters scored all brain MRI to assess reliability of the Hip-hop and PAS. Brain MRIs were obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database.Results:The patients with early-onset AD had significantly more pronounced mediotemporal and also parietal atrophy bilaterally compared to the controls (both p < 0.01). The patients with late-onset AD had significantly more pronounced only mediotemporal atrophy bilaterally compared to the controls (p < 0.000001), but parietal lobes were the same. Intra-rater and inter-rater reliability of both visual scales Hip-hop and PAS were almost perfect in all cases (weighted-kappa value ranged from 0.90 to 0.99).Conclusion:While mediotemporal atrophy detected using Hip-hop is universal across the whole AD age spectrum, parietal atrophy detected using PAS is worth rating only in early-onset AD. Hip-hop and PAS are very reliable MRI visual scales.

Brain Atrophy and Leukoaraiosis Correlate with Futile Stroke Thrombectomy

IntroductionAlthough mechanical thrombectomy (MT) is a proven therapy for acute large vessel occlusion strokes, futile recanalization in the elderly is common and costly. Strategies to minimize futile recanalization may reduce unnecessary thrombectomy transfers and procedures. We evaluated whether a simple and rapid visual assessment of brain atrophy and leukoaraiosis on a plain head CT correlates with futile stroke recanalization in the elderly. MethodsConsecutive stroke patients admitted for thrombectomy, older than 65 years of age, all with TICI 2b/3 recanalization rates were retrospectively studied from multiple comprehensive stroke centers. Brain atrophy and leukoaraiosis were visually analyzed from pre-intervention plain head CTs using a simplified scheme based on validated scales. Baseline demographics were collected and the primary outcome measure was 90-day modified Rankin score (mRS). Cochran-Armitage trend test was applied in analyzing the association of the severity of brain atrophy and leukoaraiosis with 90-day mRS. ResultsBetween 2017 and 2019, 175 patients > 65 years who underwent thrombectomy with TICI 2b/3 recanalization from two comprehensive stroke centers were evaluated. The median age was 77 years. IV-tPA was given in 59% of patients, average initial NIHSS was 19, average baseline mRS was 0.77 and median time to recanalization was 300 minutes. Age and severity of atrophy/leukoaraiosis was categorized into three groups of increasing severity and associated with 90 day mRS 0-3 rates of 62%, 49% and 41% (p=0.037) respectively. ConclusionsA simplified, visual assessment of the degree of brain atrophy and leukoaraiosis measured on plain head CT correlates with futile recanalization in patients age >65 years. Although additional validation is needed, these findings suggest that brain atrophy and leukoaraiosis may have value as a surrogate marker of prestroke functional status. In doing so, simplified visual plain head CT grading scales may minimize elderly futile recanalization.

Assessment of brain atrophy and lesion burden with clinical outcomes in multiple sclerosis real-world practice: The NeuroSTREAM MSBase retrospective, longitudinal study (2699)

Assessment of brain atrophy and lesion burden with clinical outcomes in multiple sclerosis real-world practice: The NeuroSTREAM MSBase retrospective, longitudinal study (2699)

The Clinical Value of Structural and Functional Brain Connectivity MR Biomarkers in Alzheimer's Disease

Background: At present, clinical use of MRI in Alzheimer’s disease (AD) is mostly focused on the assessment of brain atrophy, namely in the hippocampal region. Despite this, multiple biomarkers reflecting structural and functional brain connectivity changes have shown promising results in the assessment of AD. To help identify the most relevant ones that may stand a chance of being used in clinical practice, we compared multiple biomarker in terms of their value to discriminate AD from healthy controls and analyzed their age dependency. Methods: 20 AD patients and 20 matched controls underwent MRI-scanning (3T GE), including T1-weighted, diffusion-MRI, and resting-state-fMRI (rsfMRI). Whole-brain, white-matter, gray-matter, cortical-gray-matter and hippocampi volumes were measured using icobrain. rsfMRI between regions of the default-mode-network (DMN) was assessed using group independent-component-analysis. Median diffusivity and kurtosis were determined in gray and white-matter.Logistic-Regression and Random-Forest models were trained to classify AD-status based on different features and feature-groups. Results: Hippocampal and DMN features involving the medial-Pre-Frontal-Cortex (mPFC) showed the strongest differences between AD-patients and controls. mPFC-DMN-features, WM volume, and relative hippocampal asymmetry showed only an association with AD-status (p <0.05) but not with age. Whole-brain volume, hippocampi volumes, and DTI/DKI features showed an association both with age and AD-status. Smallest-hippocampus-volume was the most discriminative feature. The best performance (accuracy:0.77, sensitivity:0.77, specificity:0.77) was obtained with an RF-model combining the best feature from each feature-group (smallest hippocampus volume, WM volume, median GM AxD and lTPJ-mPFC connectivity) and age. Conclusions: Brain-connectivity changes are reflected in multiple MRI-biomarkers. Inclusion of structural and functional connectivity biomarkers in addition to hippocampal volumes can contribute to a higher diagnostic accuracy and may provide a more complete assessment of the clinical status of each patient.

Voxel-Based Morphometry in Frontotemporal Dementia

Frontotemporal dementia (FTD) is a clinically, genetically and pathologically heterogenous neurodegenerative disorder. FTD is characterized by a focal atrophy, which makes it a promising candidate for study using voxel-based morphometry (VBM). Visual assessment of magnetic resonance imaging of the brain is subjective and often depends on the researcher’s experience, which reduces its diagnostic value. VBM, on the other hand, allows quantitative assessment of brain atrophy, which increases the accuracy and allows to identify the earliest stages of the neurodegenerative process. This review will cover the utility of VBM in the study of the neuroanatomical foundations of the disease, identify the atrophy patterns specific to each variants of FTD and analyze the role of VBM in diagnosis of clinical and preclinical stages of the disease.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for a protocol concerning routinely used magnetic resonance imaging in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis that is essential for the detection and follow-up of the disease. OBJECTIVE: The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of their recommendations for investigations routinely conducted in magnetic resonance imaging departments in patients with multiple sclerosis. This version includes new data and practical comments for electroradiology technologists and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics necessary for establishing a diagnosis, as well as for MS patient monitoring, which directly translates into significant clinical decisions. INTRODUCTION: Multiple sclerosis (MS) is a chronic immune mediated inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in a CNS destruction process disseminated in time (DIT) and space (DIS). MRI detects focal lesions in the white and grey matter with high sensitivity (although with significantly lower specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume (GMV) and white matter volume (WMV) as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, and hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in MR techniques, as well as advances in postprocessing the obtained data, has driven the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MR imaging is unquestionably the best diagnostic tool available to follow up the course of the disease and support clinicians in choosing the most appropriate treatment strategy for their MS patient. However, to diagnose and follow up MS patients on the basis of MRI in accordance with the latest standards, the MRI study must adhere to certain quality criteria. Such criteria are the subject of this paper.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for the routinely used magnetic resonance imaging protocol in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions.MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies.MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper.

The Usefulness of MRI in Assessing Brain Atrophy for People Suffer from Multiple Sclerosis

The Usefulness of MRI in Assessing Brain Atrophy for People Suffer from Multiple Sclerosis

Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART)

Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Recently, primary age-related tauopathy (PART) has been described as a new anatomopathological disorder where NFTs are the main feature in the absence of neuritic plaques. However, since PART has mainly been studied in post-mortem patient brains, not much is known about the clinical or neuroimaging characteristics of PART. Here, we studied the clinical brain imaging characteristics of PART focusing on neuroanatomical vulnerability by applying a previously validated multiregion visual atrophy scale. We analysed 26 cases with confirmed PART with paired clinical magnetic resonance imaging (MRI) acquisitions. In this selected cohort we found that upon correcting for the effect of age, there is increased atrophy in the medial temporal region with increasing Braak staging (r = 0.3937, p = 0.0466). Upon controlling for Braak staging effect, predominantly two regions, anterior temporal (r = 0.3638, p = 0.0677) and medial temporal (r = 0.3836, p = 0.053), show a trend for increased atrophy with increasing age. Moreover, anterior temporal lobe atrophy was associated with decreased semantic memory/language (r = − 0.5823, p = 0.0056; and r = − 0.6371, p = 0.0019, respectively), as was medial temporal lobe atrophy (r = − 0.4445, p = 0.0435). Overall, these findings support that PART is associated with medial temporal lobe atrophy and predominantly affects semantic memory/language. These findings highlight that other factors associated with aging and beyond NFTs could be involved in PART pathophysiology.

Computed Tomography Assessment of Brain Atrophy in Centenarians

The aim of our study was to compare the degree of brain atrophy in centenarians and in seniors 70–99 years old. The study group consisted of 23 patients aged 100–106 years. The control group consisted of 90 patients, 30 in each age subgroup 90–99, 80–89, 70–79. In all the patients, the brain atrophy linear parameters were measured on computed tomography scans, in relation to both “subcortical atrophy”, evaluated as progressive widening of the ventricular system, and “cortical atrophy”, defined as widening of subarachnoid space. Secondary indices based on the parameters were calculated. Correlations between the above parameters/indices and age were tested. Significantly different values between the centenarians and the control group were found in the brain atrophy parameters: A, B, C, E, FI, ICR, ICL, SW, CFW, F/A ‘frontal horn index’, A/G ‘Evans index’, D/A ‘ventricular index’, H/E ‘cella media Schiersmann index’, A+B ‘Huckman number’. Correlations between parameter/index and age were found for: A, B, C, FI, ICR, ICL, SW, F/A ‘frontal horn index’, A/G ‘Evans index’, D/A ‘ventricular index’, H/E ‘cella media Schiersmann index’, A+B ‘Huckman number’. Brain atrophy associated with aging is a continuously advancing process, affecting centenarians even more than people before the “magic” threshold of 100 years.

Voluntary wheel running delays brain atrophy in aged mice.

BACKGROUND: Physical exercises have been shown to be a surprisingly effective strategy to take advantage of the brain’s natural capacity for plasticity, and prevent brain degeneration in mouse histological studies. In vivo magnetic resonance microscopy (MRM) provides highly resolved anatomical images and allows quantitative assessment of brain atrophy in the aged mouse model.OBJECTIVE: The aim of the present study was to investigate, through the effects of 10 weeks voluntary wheel running, the mouse’s brain atrophy.METHODS: Sixteen C57BL/6J mice, aged 21 months, were randomized to the exercise or sedentary group. Each mouse was scanned in a 7.0-T MRM scanner at two time points: 22 months old baseline and a follow-up three months later. Multi-atlas based brain segmentation approach was used to obtain volumes of 39 brain regions.RESULTS: The results showed that mice in the exercise group had less brain atrophy compared with the mice in the sedentary group.CONCLUSIONS: The results provide new insights into exercise induced brain plasticity in aged animals.

The role of MR volumetry in brain atrophy assessment in multiple sclerosis: A review of the literature.

We review the current role of magnetic resonance (MR) volumetry as a meaningful indicator of neurodegeneration and clinical disease progression in multiple sclerosis (MS) patients. Based on a review of the current literature we summarize the mechanisms that contribute to brain atrophy. We present the newest magnetic resonance imaging (MRI)-based methods used in atrophy quantification. We also analyze important biological factors which can influence the accuracy of brain atrophy evaluation. Evidence shows that measures of brain volume (BV) have the potential to be an important determinant of disease progression to a greater extent than conventional lesion assessment. Finally, scientific reports concerning limitations of MRI-based volumetry that affect its implementation into routine clinical practice are also reviewed. The technical challenges that need to be overcome include creating a standardized protocol for image acquisition - a fully automated, accurate and reproducible method that allows comparison in either single-center or multicenter settings. In the near future, quantitative MR research will probably be the basic method used in neurology to monitor the rate of atrophic processes and clinical deterioration in MS patients, and to evaluate the results of treatment.

Medial temporal lobe atrophy and posterior atrophy scales normative values.

ObjectivesThe medial temporal lobe atrophy (MTA) and the posterior atrophy (PA) scales allow to assess the degree hippocampal and parietal atrophy from magnetic resonance imaging (MRI) scans. Despite reliable, easy and widespread employment, appropriate normative values are still missing. We aim to provide norms for the Italian population.MethodsTwo independent raters assigned the highest MTA and PA score between hemispheres, based on 3D T1-weighted MRI of 936 Italian Brain Normative Archive subjects (age: mean ± SD: 50.2 ± 14.7, range: 20–84; MMSE>26 or CDR = 0). The inter-rater agreement was assessed with the absolute intraclass correlation coefficient (aICC). We assessed the association between MTA and PA scores and sociodemographic features and APOE status, and normative data were established by age decade based on percentile distributions.ResultsRaters agreed in 90% of cases for MTA (aICC = 0.86; 95% CI = 0.69–0.98) and in 86% for PA (aICC = 0.82; 95% CI = 0.58–0.98). For both rating scales, score distribution was skewed, with MTA = 0 in 38% of the population and PA = 0 in 52%, while a score ≥ 2 was only observed in 12% for MTA and in 10% for PA. Median denoted overall hippocampal (MTA: median = 1, IQR = 0–1) and parietal (PA: median = 0, IQR = 0–1) integrity. The 90th percentile of the age-specific distributions increased from 1 (at age 20–59) for both scales, to 2 for PA over age 60, and up to 4 for MTA over age 80. Gender, education and APOE status did not significantly affect the percentile distributions in the whole sample, nor in the subset over age 60.ConclusionsOur normative data for the MTA and PA scales are consistent with previous studies and overcome their main limitations (in particular uneven representation of ages and missing percentile distributions), defining the age-specific norms to be considered for proper brain atrophy assessment.

Brain Atrophy Is Associated with Disability Progression in Patients with MS followed in a Clinical Routine.

The assessment of brain atrophy in a clinical routine is not performed routinely in multiple sclerosis. Our aim was to determine the feasibility of brain atrophy measurement and its association with disability progression in patients with MS followed in a clinical routine for 5 years. A total of 1815 subjects, 1514 with MS and 137 with clinically isolated syndrome and 164 healthy individuals, were collected retrospectively. Of 11,794 MR imaging brain scans included in the analysis, 8423 MRIs were performed on a 3T, and 3371 MRIs, on a 1.5T scanner. All patients underwent 3D T1WI and T2-FLAIR examinations at all time points of the study. Whole-brain volume changes were measured by percentage brain volume change/normalized brain volume change using SIENA/SIENAX on 3D T1WI and percentage lateral ventricle volume change using NeuroSTREAM on T2-FLAIR. Percentage brain volume change failed in 36.7% of the subjects; percentage normalized brain volume change, in 19.2%; and percentage lateral ventricle volume change, in 3.3% because of protocol changes, poor scan quality, artifacts, and anatomic variations. Annualized brain volume changes were significantly different between those with MS and healthy individuals for percentage brain volume change (P < .001), percentage normalized brain volume change (P = .002), and percentage lateral ventricle volume change (P = .01). In patients with MS, mixed-effects model analysis showed that disability progression was associated with a 21.9% annualized decrease in percentage brain volume change (P < .001) and normalized brain volume (P = .002) and a 33% increase in lateral ventricle volume (P = .004). All brain volume measures differentiated MS and healthy individuals and were associated with disability progression, but the lateral ventricle volume assessment was the most feasible.

FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer\u2019s disease

BackgroundNeurofibrillary pathology composed of tau protein is closely correlated with severity and phenotype of cognitive impairment in patients with Alzheimer’s disease and non-Alzheimer’s tauopathies. Targeting pathological tau proteins via immunotherapy is a promising strategy for disease-modifying treatment of Alzheimer’s disease. Previously, we reported a 24-week phase 1 trial on the active vaccine AADvac1 against pathological tau protein; here, we present the results of a further 72 weeks of follow-up on those patients.MethodsWe did a phase 1, 72-week, open-label study of AADvac1 in patients with mild to moderate Alzheimer’s disease who had completed the preceding phase 1 study. Patients who were previously treated with six doses of AADvac1 at monthly intervals received two booster doses at 24-week intervals. Patients who were previously treated with only three doses received another three doses at monthly intervals, and subsequently two boosters at 24-week intervals. The primary objective was the assessment of long-term safety of AADvac1 treatment. Secondary objectives included assessment of antibody titres, antibody isotype profile, capacity of the antibodies to bind to AD tau and AADvac1, development of titres of AADvac1-induced antibodies over time, and effect of booster doses; cognitive assessment via 11-item Alzheimer’s Disease Assessment Scale cognitive assessment (ADAS-Cog), Category Fluency Test and Controlled Oral Word Association Test; assessment of brain atrophy via magnetic resonance imaging (MRI) volumetry; and assessment of lymphocyte populations via flow cytometry.ResultsThe study was conducted between 18 March 2014 and 10 August 2016. Twenty-six patients who completed the previous study were enrolled. Five patients withdrew because of adverse events. One patient was withdrawn owing to noncompliance. The most common adverse events were injection site reactions (reported in 13 [50%] of vaccinated patients). No cases of meningoencephalitis or vasogenic oedema were observed. New micro-haemorrhages were observed only in one ApoE4 homozygote. All responders retained an immunoglobulin G (IgG) antibody response against the tau peptide component of AADvac1 over 6 months without administration, with titres regressing to a median 15.8% of titres attained after the initial six-dose vaccination regimen. Booster doses restored previous IgG levels. Hippocampal atrophy rate was lower in patients with high IgG levels; a similar relationship was observed in cognitive assessment.ConclusionsAADvac1 displayed a benign safety profile. The evolution of IgG titres over vaccination-free periods warrants a more frequent booster dose regimen. The tendency towards slower atrophy in MRI evaluation and less of a decline in cognitive assessment in patients with high titres is encouraging. Further trials are required to expand the safety database and to establish proof of clinical efficacy of AADvac1.Trial registrationThe studies are registered with the EU Clinical Trials Register and ClinicalTrials.gov: the preceding first-in-human study under EudraCT 2012-003916-29 and NCT01850238 (registered on 9 May 2013) and the follow-up study under EudraCT 2013-004499-36 and NCT02031198 (registered 9 Jan 2014), respectively.

Guidelines of the Polish Medical Society of radiology for the routinely used MRI protocol in patients with multiple sclerosis

Magnetic resonance imaging is widely used in diagnosing multiple sclerosis as a basic method for detecting and monitoring the disease. IntroductionPolish Medical Society of Radiology presents the second version of the recommendations for the routinely conducted MRI in multiple sclerosis, which include new data and practical remarks for radiographers and radiologists. The recommended protocol aims to improve the imaging procedure and, most importantly, to standardize conducting MRI scans in all MRI departments. This is crucial for monitoring the patients with MS, which directly contributes to essential clinical decisions. Aim of the guidelinesMultiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system (CNS) with its etiology still unknown. The fundamental requirement of the disease is the CNS destruction process disseminated in time (DIT) and space (DIS). MR imaging detects focal lesions in white and gray matter with high sensitivity and is the best way to assess brain atrophy in MS patients. It is unquestionably the best diagnostic tool to follow-up the clinical course of the disease and treatment of MS patients. However, to achieve a diagnosis based on MRI scans, and follow-up MS patients according to the latest standards, an MRI scan has to meet certain quality criteria that are the subject of this work.