Marker Of Brain Atrophy Research Articles

AT THE INTERFACE OF THE BRAIN AND ENVIRONMENT: DETERMINANTS OF COGNITIVE FUNCTION AND MOBILITY

It is hypothesized that older adults are more influenced by environmental factors due to reduced tolerance to stressors and greater cumulative exposure. The role of environmental factors in brain and cognitive aging, specifically, has not been well studied. In this symposium, we highlight novel work at the interface of the environment and the brain in aging. The presentations assess varying aspects of the environment/brain interface within three cohorts. Two of the presentations focus on the environment as a risk factor for brain or cognitive aging. Sara Godina will present analyses of neighborhood socioeconomic status and neuroimaging markers of brain atrophy within the Health ABC Study, with the aim of understanding documented associations of neighborhood socioeconomic status with cognitive function. Jessica Finlay will present data from the REGARDS study linking weather conditions with cognitive changes. Climate influences social and physical activities and could thereby, impact cognitive aging. The brain also serves to process and integrate environmental data in order to direct behaviors in an adaptive manner. Two of the presentations assess how cognitive aging may impact individuals’ interactions with the environment. Using residential histories of participants in the Cardiovascular Health Study, Jonathan Platt will explore how cognitive trajectories change in relation to changes in residence. These analyses will demonstrate how residential changes may be either supportive or detrimental to cognitive aging. Finally, Andrea Rosso will present data from the Health ABC that demonstrates how cognitive aging may determine the vulnerability of older individuals to environmental influences on mobility declines.

Greater depressive symptoms, cognition, and markers of brain aging: Northern Manhattan Study.

We examined whether greater depressive symptoms were associated with domain-specific cognitive performance, change in cognition, and MRI markers of brain atrophy and subclinical cerebrovascular disease in a diverse sample of older adults from the Northern Manhattan Study. Data were analyzed from the Northern Manhattan Study, a prospective cohort study of mostly Caribbean Hispanic, stroke-free, older adults. A total of 1,111 participants had baseline measures of depressive symptoms, measured as the Center of Epidemiological Studies-Depression Scale, MRI markers, and cognitive function. A Center of Epidemiological Studies-Depression score ≥16 was considered indicative of greater depressive symptoms. Multivariable linear and logistic regression models were used to examine the associations of interest. At baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographic, vascular risk factor, behavioral, and antidepressive medication variables (β [95% confidence interval] = -0.21 [-0.33 to -0.10], p = 0.0003). Greater depressive symptoms were also associated with smaller cerebral parenchymal fraction (β [95% confidence interval] = -0.56 [-1.05 to -0.07], p = 0.02) and increased odds of subclinical brain infarcts (odds ratio [95% confidence interval] = 1.55 [1.00-2.42], p = 0.05), after adjustment for sociodemographic, behavioral, and vascular risk factor variables. Greater depressive symptoms were not significantly associated with white matter hyperintensity volume, hippocampal volume, or change in cognition over an average of 5 years. Results were unchanged when stabilized inverse probability weights were applied to address selective attrition during the study period. In this sample of mostly Caribbean Hispanic, stroke-free, older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts.

Correlation between the corpus callosum index and brain atrophy, lesion load, and cognitive dysfunction in multiple sclerosis

BackgroundThe corpus callosum index (CCI) can be easily and reliably obtained from conventional magnetic resonance imaging (MRI) and has been proposed as a possible marker of brain atrophy in MS. However, further validation of its correlation with volumetric measurements is still warranted. ObjectiveTo assess the correlation of the CCI with the corpus callosum volume (CCV), brain and lesion volumes, and level of disability in MS. MethodsCross-sectional, exploratory study including patients with relapsing-remitting MS. Clinical assessment comprised of physical and cognitive disability scales. MRI parameters included conventional volumetric measurements, the CCI (manual), and the CCV (automated). ResultsTwenty-four patients were included. There was a strong correlation between the CCI and CCV. The CCI correlated strongly with the white matter and lesion volumes, and moderately with the whole brain volume and scores on the Paced Auditory Serial Addition Test and MS Functional Composite. There were no correlations between the CCI and either gray matter volume or scores on the Expanded Disability Status Scale, the 9-Hole Peg Test, or the Timed 25-Foot Walk test. ConclusionThe findings support the validity of the CCI as an easy-to-obtain marker of brain atrophy, lesion load, and cognitive dysfunction in patients with MS.

Neurofilament light protein in blood predicts regional atrophy in Huntington disease.

ObjectiveNeurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers.MethodsWe examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 years in HD gene expansion carriers.ResultsAfter controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical gray matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital gray matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression.ConclusionsThese findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathologic neuronal change.

Structural brain changes and all-cause mortality in the elderly population-the mediating role of inflammation.

While MRI brain changes have been relatedto mortality during ageing, the role of inflammation in this relationship remains poorly understood. Hence, this study aimed to investigate the impact of MRI changes on all-cause mortality and the mediating role of cytokines. All-cause mortality was evaluated in 268 community dwelling elderly (age 65-83years) in the MEMO study (Memory and Morbidity in Augsburg elderly). MRI markers of brain atrophy and cerebral small vessel disease (SVD), C-reactive protein(CRP) and a panel of cytokines in serum were assessed. Cox proportional hazard models were used to estimate the association of MRI changes with survival over 9years. Regression models were used to assess the hypothesis that inflammation is mediating the relationship between MRI-brain changes and mortality. In total, 77 (29%) deaths occurred during a mean follow up of 9years. After adjusting for confounders, the degree of global cortical atrophy and the level of the cytokines CRP, TNF-α and IL-8 were of higher significance in study participants who had died at follow-up in comparison to survivors. In Cox proportional hazard models, higher degrees of global cortical atrophy (HR 1.56, p=0.003) and regional atrophy of the temporal lobe (HR 1.38, p=0.011) were associated with a significantly increased risk of mortality. Mediation analyses revealed a partial mediation by IL-6 and IL-8 of the effects of global cortical atrophy on mortality. Global cortical brain atrophy is a significant indicator of survival in the elderly. Our study supports a possible role for inflammation in the atrophy pathogenesis. If replicated in other samples, IL-6 and IL-8 level assessment may improve risk prognosis for mortality.

Preexisting cognitive impairment in intracerebral hemorrhage.

Preexisting cognitive impairment is a predictor of cognitive decline after ischemic stroke, but evidence in intracerebral hemorrhage (ICH) is limited. We aimed to determine the prevalence of premorbid cognitive impairment in patients with ICH. We included patients with acute ICH. Pre-ICH cognitive impairment was determined based on the results of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) that uses information from close relatives. Patients were assessed as having been cognitively impaired with an IQCODE score of ≥3.44; an IQCODE ≥4.00 indicated pre-ICH dementia. CT and MRI images were reviewed to determine the extent of white matter lesions and to measure the radial width of the temporal horn as marker of brain atrophy. We investigated differences of cardiovascular risk factors and imaging data between patients with and without pre-ICH cognitive impairment using correlation analyses, uni- and multivariable regression models. Functional neurological state was assessed using the modified Rankin Scale (mRS). The mRS was dichotomized at the level of 3, and a premorbid mRS of 0-2 was considered as functional independency. Among the 89 participants, median age was 70years (interquartile range 58-78) and 52 (58.4%) were male. IQCODE indicated pre-ICH cognitive impairment in 18.0% (16 of 89), and 83.1% were functionally independent before ICH. Cognitive impairment was associated with a premorbid mRS≥3 (chi squared test, P=0.009). In multivariable analysis, prior stroke/transient ischemic attack (OR 18.29, 95%-CI 1.945-172.033, P=.011) and hematoma volume (OR 0.90, 95%-CI 0.812-0.991, P=.033) were independently associated with pre-ICH cognitive impairment. In conclusion, cognitive impairment frequently precedes ICH. A higher frequency of cerebrovascular events suggests a role of vascular processes in the development of cognitive impairment before ICH.

Apnea-hypopnea index, nocturnal arousals, oxygen desaturation and structural brain changes: A population-based study

Sleep apnea has been related to brain changes such as atrophy. However, which component of sleep apnea, the apnea-hypopnea index (AHI), nocturnal oxygen desaturation or arousals, can explain this association is unclear. In this large population-based study (n=681, mean age 62.1 years), we investigated the associations of AHI, nocturnal oxygen desaturation and arousals with global and regional gray matter and white matter volumes and with white matter lesion volumes. All participants underwent one night of polysomnography and MRI scanning of their brain. Gray matter, white matter and white matter lesion volumes adjusted for intracranial volume were studied as markers of brain atrophy. Nocturnal oxygen desaturation was related to whole brain white matter atrophy independent of covariates (multivariable adjusted B=−8.3, 95% CI=−16.7; −0.02). This association was most prominently reflected in the association between more oxygen desaturation and a smaller white matter parietal volume (B=−3.95ml, 95% CI=−6.02; −1.88). Furthermore, oxygen desaturation was related to a smaller hippocampus (B=−0.22ml, 95% CI=−0.42; −0.01). Although a higher AHI was related to smaller parietal gray (B=−0.05, 95% CI=−0.09; −0.004) and white matter (B=−0.06, 95% CI=−0.12; −0.10) volumes, these associations disappeared when adding oxygen desaturation to the model. We did not find a relation between arousals and gray and white matter brain atrophy and white matter lesion volumes. This suggests that oxygen desaturation mainly explains the association between sleep apnea and brain damage.

Effectiveness of Cortical Atrophy Scale and Indirect Indices of Brain Atrophy to Predict Chronic Subdural Hematoma in Older Patients.

ObjectiveTo determine whether baseline cerebral atrophy can predict the rate of future chronic subdural hematoma (CSDH) after head trauma and compare indirect markers of brain atrophy with volumetric analysis of computed tomography (CT).MethodsSingle institution case-control study involving 1,476 patients who visited our hospital after head trauma from January 2009 to December 2014. Forty-one patients with delayed CSDH were identified and age, gender matched 41 patients were selected as control group. Both volumetric analyze on CT and Evans index, frontal horn index, bicaudate ratio, sylvian fissure ratio and cortical atrophy scale of 82 patients were estimated by different raters and relationship of those factors with CSDH was analyzed.ResultsEvery indirect indices except cortical atrophy scale were not enough to give a good estimate of CSDH. Brain atrophy and cortical atrophy scale were predisposing factors of CSDH on multivariate analysis with statistical significance.ConclusionBrain atrophy was a potential prognostic factor of CSDH after trauma. In practice, patients with a value of cortical atrophy scale over moderate grade needed more attention for CSDH.

P119. Correlation of ventricular diameter and cognitive dysfunction in patients with IPD – Comparison of transcranial sonography and MRI

Background In the course of idiopathic Parkinson's disease (IPD) 30% of patients develop dementia yielding to new challenges in diagnosis and therapy. Several studies in multiple sclerosis or HIV patients indicated a correlation of ventricular diameter as a marker of brain atrophy and a decline of cognitive function. Objective The aim of this study was to evaluate if ventricular diameter measured by TCS and MR-imaging is a marker of brain atrophy and if it is correlated with severity of disease and cognitive dysfunction. Methods In this study 108 PD patients (64% male, 36% female; mean age: 63,64±8,24years (yrs)) and 39 controls (36% male, 64% female; mean age: 51,7±15,6yrs) underwent a T1/T2-weighted MR Imaging and TCS. The transverse diameter of the third ventricle (3v) and the frontal horns of right (rv) and left (lv) lateral ventricles were measured. Furthermore, neurological examinations, standardized motor functional (UPDRS, Webster) and cognitive (MMST, PANDA, ZVT) tests were performed. 31 individuals underwent a follow up examination after 5yrs. Results The TCS measurement of ventricular diameter significantly correlated with the MRI measurement (Spearman rank correlation, 3v: r =0.8, lv: r =0.4; p r =0.2; p r =0.49; p r =0.389; p r =0.421; p 3v : r =−0.3; p =n. s.; lv : r =−0.5; p rv: r =−0.5; p 3v : r =−0.457; p lv : r =−0.417; p rv: r =−0.261; p =n.s.). No correlation between motor function and ventricular diameter was found. In 5-year follow-up all individuals showed a significant increase of lateral ventricular diameter (rv+lv: p Conclusions Our results suggest that TCS measurement of ventricular diameter represents a quick, low priced and simple method as a surrogate marker of brain atrophy associated in IPD with age and cognitive function. Future investigations may define the value of TCS ventricular diameter measurement for evaluation of cognitive dysfunction in IPD in routine clinical practice.

Nutrient patterns and brain biomarkers of Alzheimer's disease in cognitively normal individuals.

Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. Cross-sectional study. Manhattan (broader area). Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-β, Aβ) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB and Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE and PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants and Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12 and D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12 and D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE and PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants and Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified 'AD-protective' nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter. Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Aβ and associated neuronal impairment.

A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume

In patients with malignant middle cerebral artery infarction (MMI) decompressive surgery within 48 h improves functional outcome. In this respect, early identification of patients at risk of developing MMI is crucial. While the acute diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high predictive values, the potential impact of preexisting brain atrophy on the course of space-occupying middle cerebral artery (MCA) infarction and the development of MMI remains unclear. We tested the hypothesis that the combination of the acute DWI lesion volume with simple measures of brain atrophy improves the early prediction of MMI. Data from a prospective, multicenter, observational study, which included patients with acute middle cerebral artery main stem occlusion studied by MRI within 6 h of symptom onset, was analyzed retrospectively. The development of MMI was defined according to the European randomized controlled trials of decompressive surgery. Acute DWI lesion volume, as well as brain and cerebrospinal fluid volume (CSF) were delineated. The intercaudate distance (ICD) was assessed as a linear brain atrophy marker by measuring the hemi-ICD of the intact hemisphere to account for local brain swelling. Binary logistic regression analysis was used to identify significant predictors of MMI. Cut-off values were determined by Classification and Regression Trees analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the resulting models were calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle cerebral artery infarctions patients had higher National Institutes of Health Stroke Scale scores on admission and presented more often with combined occlusion of the internal carotid artery and MCA. There were no differences in brain and CSF volume between the two groups. Diffusion weighted imaging lesion volume was larger (p < 0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients. Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to predict the development of MMI were DWI lesion volume > 87 ml and hemi-ICD ≤ 9.4 mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93 vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to 1/15 (7 %), while there were only slight changes in specificity, sensitivity and NPV. The absolute number of correct classifications increased by 4 (3.4 %). The integration of hemi-ICD as a linear marker of brain atrophy, that can easily be assessed in an emergency setting, may improve the prediction of MMI by lesion volume based predictive models.

Automated algorithm to measure changes in medial temporal lobe volume in Alzheimer disease

The change in volume of anatomic structures is as a sensitive indicator of Alzheimer disease (AD) progression. Although several methods are available to measure brain volumes, improvements in speed and automation are required. Our objective was to develop a fully automated, fast, and reliable approach to measure change in medial temporal lobe (MTL) volume, including primarily hippocampus. The MTL volume defined in an atlas image was propagated onto each baseline image and a level set algorithm was applied to refine the shape and smooth the boundary. The MTL of the baseline image was then mapped onto the corresponding follow-up image to measure volume change (ΔMTL). Baseline and 24 months 3D T1-weighted images from the Alzheimer Disease Neuroimaging Initiative (ADNI) were randomly selected for 50 normal elderly controls (NECs), 50 subjects with mild cognitive impairment (MCI) and 50 subjects with AD to test the algorithm. The method was compared to the FreeSurfer segmentation tools. The average ΔMTL (mean±SEM) was 68±35mm(3) in NEC, 187±38mm(3) in MCI and 300±34mm(3) in the AD group and was significantly different (p<0.0001) between all three groups. The ΔMTL was correlated with cognitive decline. Results for the FreeSurfer software were similar but did not detect significant differences between the MCI and AD groups. This novel segmentation approach is fully automated and provides a robust marker of brain atrophy that shows different rates of atrophy over 2 years between NEC, MCI, and AD groups.

Circulating Omega‐3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study

BackgroundConsumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega‐3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI.Methods and ResultsIn the community‐based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992–1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992–1993 and related to cross‐sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long‐chain omega‐3 PUFA quartile. Higher long‐chain omega‐3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate‐chain omega‐3 PUFA alpha‐linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha‐linolenic acid intake.ConclusionsAmong older adults, higher phospholipid long‐chain omega‐3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long‐chain omega‐3 PUFAs, on brain health in later life. The role of plant‐derived alpha‐linolenic acid in brain health requires further investigation.

Identifying novel CSF markers of brain atrophy in Alzheimer's disease and mild cognitive impairment using a multiplex panel of analytes

Identifying novel CSF markers of brain atrophy in Alzheimer's disease and mild cognitive impairment using a multiplex panel of analytes

Genetic and brain atrophy markers associated with different psychological phenotypes within ADNI

room. Patients with Alzheimer’s disease (AD) typically have difficulty with tasks requiring ASA and anatomical regions implicated in ASA in the healthy brain are vulnerable in AD, suggesting that ASAmay provide a window on AD pathophysiology. Methods: Here we studied the brain mechanism of the ’cocktail party effect’ using 3T fMRI in a cohort of patients fulfilling consensus criteria for typical AD in relation to age-matched healthy subjects.We designed a ’sparse’ image acquisition, passive listening paradigm to minimise extraneous cognitive or task-related attentional demands, control low-level auditory perceptual features and optimise signal detection. We reasoned that the cocktail party effect would be captured by the differential ASA demands during processing of sound conditions where the auditory target was a learned template (one’s own name) versus a comparably acoustically complex but unfamiliar sound object (one’s own name spectrally rotated). Subjects heard four stimulus conditions: i) their own name interleaved with babble, ii) own name superimposed on babble, iii) own name spectrally rotated (rendered unrecognisable) and interleaved with babble, or iv) own name spectrally rotated and superimposed on babble. Results: Compared with healthy older controls, AD patients showed heightened activation in posterior hippocampus during ’cocktail party’ processing. Conclusions: Our findings suggest that ASA is a model of generic cortical information processing that can be used to probe obligatory pathophysological mechanisms of AD, including abnormally heightened or compensatory processes. This work goes beyond the traditional emphasis on higher cognitive and mnestic functions in AD: besides illuminating an important but poorly understood class of perceptual symptoms, such work promises novel insights into neural network dysfunction underpinning AD.

Automated Determination of Brain Parenchymal Fraction in Multiple Sclerosis

Brain atrophy is a manifestation of tissue damage in MS. Reduction in brain parenchymal fraction is an accepted marker of brain atrophy. In this study, the approach of synthetic tissue mapping was applied, in which brain parenchymal fraction was automatically calculated based on absolute quantification of the tissue relaxation rates R1 and R2 and the proton attenuation. The BPF values of 99 patients with MS and 35 control subjects were determined by using SyMap and tested in relationship to clinical variables. A subset of 5 patients with MS and 5 control subjects were also analyzed with a manual segmentation technique as a reference. Reproducibility of SyMap was assessed in a separate group of 6 healthy subjects, each scanned 6 consecutive times. Patients with MS had significantly lower BPF (0.852 ± 0.0041, mean ± SE) compared with control subjects (0.890 ± 0.0040). Significant linear relationships between BPF and age, disease duration, and Expanded Disability Status Scale scores were observed (P < .001). A strong correlation existed between SyMap and the reference method (r = 0.96; P < .001) with no significant difference in mean BPF. Coefficient of variation of repeated SyMap BPF measurements was 0.45%. Scan time was <6 minutes, and postprocessing time was <2 minutes. SyMap is a valid and reproducible method for determining BPF in MS within a clinically acceptable scan time and postprocessing time. Results are highly congruent with those described using other methods and show high agreement with the manual reference method.

Total-tau in cerebrospinal fluid of patients with multiple sclerosis decreases in secondary progressive stage of disease and reflects degree of brain atrophy

Introduction. Tau protein is a potential marker of neuronal damage. The aim of the study is to investigate its potential role as a marker of brain atrophy in multiple sclerosis (MS).Materials and methods. Cerebrospinal fluid (CSF) and blood samples were collected from 48 patients with multiple sclerosis. Total-tau (t-tau) and phospho181Thr-tau (p-tau) concentrations were assayed with commercially available INNOTEST® hTAU Ag and INNOTEST® phospho181Thr-tau(181P) and correlated with indices of brain atrophy in magnetic resonance imaging (MRI) and clinical characteristics of the study population.Results. T-tau concentration in CSF was significantly higher in relapsing-remitting (RR) compared to secondary progressive (SP) MS patients (P = 0.01). Brain parenchymal fraction (BPF) was significantly decreased in SP patients (P = 0.002). BPF in the whole study population correlated inversely with Expanded Disability Status Scale (EDSS) (r = –0.51, P = 0.0002) and Multiple Sclerosis Severity Score (MSSS) (r = –0.42, P = 0.002). T-tau in CSF in the whole patient group correlated inversely with EDSS (r = –0.58, P = 0.0006).Conclusions. The results of our study suggest that total-tau concentration in CSF in a MS population decreases in the course of disease and reflects degree of parenchymal brain loss.

Circulating IL-6 and CRP are associated with MRI findings in the elderly

The relation between inflammation and brain MRI findings in the elderly remains poorly known. We investigated the association of circulating interleukin-6 (IL-6) and C-reactive protein (CRP) levels with baseline and longitudinal white matter hyperintensities (WMH), silent brain infarction, and brain volumes in community-dwelling elderly free of dementia. We included 1,841 participants aged 65 to 80 years from the Three City-Dijon cohort. Participants followed an MRI examination at baseline and after a 4-year follow-up (n = 1,316). IL-6 and CRP concentrations were measured at baseline from fasting blood samples. WMH were detected with an automatic imaging processing method and gray matter, hippocampal, white matter, and CSF volumes were estimated with voxel-based morphometry. Silent brain infarctions were assessed visually and defined as focal lesions of ≥3 mm in the absence of stroke. We used analysis of covariance and logistic regression to model the associations between inflammatory biomarkers and brain MRI findings adjusting for potential confounders. In cross-sectional analyses, higher IL-6 levels were associated with higher WMH volumes (p < 0.01), lower gray matter (p = 0.001) and hippocampal (p = 0.01) volumes, and increasing CSF volumes (p = 0.002) in a dose-relationship pattern. Similar but weaker relations were observed for CRP. We observed no associations between baseline inflammatory biomarker levels and the evolution of MRI findings over 4 years. IL-6, and, to a lesser degree, CRP levels were associated with WMH severity as well as global markers of brain atrophy. These results suggest that an inflammatory process may be involved in both age-associated brain alterations.

Immune cell NT-3 expression is associated with brain atrophy in multiple sclerosis patients

While neurotrophins mediate cell survival and proliferation in the nervous system, they are also expressed within peripheral blood mononuclear cells (PBMCs) of the immunological system. In multiple sclerosis (MS) neurotrophins released from PBMCs might play a neuroprotective role, delaying neurodegeneration within central nervous system. We aimed for identifying the link between neurotrophins' PBMCs expression and brain atrophy markers in relapsing-remitting MS (RRMS) patients. We have found that neurotrophin-3 PBMCs concentration is strongly correlated with brain-parenchymal fraction and corpus callosum cross-sectional area, which are well-established brain atrophy measures. Thus, PBMC-derived neurotrophin-3 might exert a direct or indirect neuroprotective effect in MS.

Width of the third ventricle assessed by transcranial sonography can monitor brain atrophy in a time- and cost-effective manner - Results from a longitudinal study on 500 subjects

Ventricular width and its enlargement over time are discussed as promising markers for preclinical brain atrophy. The aim of our study was to define whether brain atrophy can reliably be monitored by transcranial ultrasound (TCS). In a prospective longitudinal trial over 5 years, 500 healthy persons were examined by a standardized protocol with TCS in addition to an extensive cognitive testing using the Consortium to Establish a Registry of Alzheimer's Disease — Neuropsychological Testing (CERAD-NP). TCS displayed the third ventricle in 96% of all cases at the follow-up with a high intra-individual reproducibility and excellent inter-rater coefficient (0.992). The mean diameter of the third ventricle in subjects with a cognitive decline was significantly wider (6 mm ± 2) than in subjects with normal cognitive testing results (4.6 mm ± 1.8). We demonstrated that the width of the third ventricle, as a marker of brain atrophy can reliably be monitored by using TCS as a non-invasive, time- and cost-effective method. We provide evidence that the assessed width of the third ventricle can differentiate between subjects with a normal cognitive performance and subjects with a cognitive decline. TCS may be a useful screening tool in the early diagnosis of cognitive decline.