Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations.

Background: Global brain atrophy is present in normal aging and different neurodegenerative disorders such as Alzheimer's disease (AD) and is becoming widely used to monitor disease progression.

Summary: The brain volume/cerebrospinal fluid index (BV/CSF index) is validated in this study as a measurement of global brain atrophy. We tested the ability of the BV/CSF index to detect global brain atrophy, investigated the influence of confounders, provided normative values and cut-offs for mild, moderate and severe brain atrophy, and studied associations with different outcome variables.

Quantitative validation of a visual rating scale for frontal atrophy: associations with clinical status, APOE e4, CSF biomarkers and cognition.

Objectives: To validate a visual rating scale of frontal atrophy with quantitative imaging and study its association with clinical status, APOE ε4, CSF biomarkers, and cognition.

Methods: The AddNeuroMed and ADNI cohorts were combined giving a total of 329 healthy controls, 421 mild cognitive impairment patients, and 286 Alzheimer's disease (AD) patients. Thirty-four patients with frontotemporal dementia (FTD) were also included.

Early astrocytosis in autosomal dominant Alzheimer's disease measured in vivo by multi-tracer positron emission tomography.

Studying autosomal dominant Alzheimer's disease (ADAD), caused by gene mutations yielding nearly complete penetrance and a distinct age of symptom onset, allows investigation of presymptomatic pathological processes that can identify a therapeutic window for disease-modifying therapies. Astrocyte activation may occur in presymptomatic Alzheimer's disease (AD) because reactive astrocytes surround β-amyloid (Aβ) plaques in autopsy brain tissue. Positron emission tomography was performed to investigate fibrillar Aβ, astrocytosis and cerebral glucose metabolism with the radiotracers (11)C-Pittsburgh compound-B (PIB), (11)C-deuterium-L-deprenyl (DED) and (18)F-fluorodeoxyglucose (FDG) respectively in presymptomatic and symptomatic ADAD participants (n = 21), patients with mild cognitive impairment (n = 11) and sporadic AD (n = 7).

A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging.

Many genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus.

The Effect of Age Correction on Multivariate Classification in Alzheimer's Disease, with a Focus on the Characteristics of Incorrectly and Correctly Classified Subjects.

The similarity of atrophy patterns in Alzheimer's disease (AD) and in normal aging suggests age as a confounding factor in multivariate models that use structural magnetic resonance imaging (MRI) data. To study the effect and compare different age correction approaches on AD diagnosis and prediction of mild cognitive impairment (MCI) progression as well as investigate the characteristics of correctly and incorrectly classified subjects. Data from two multi-center cohorts were included in the study [AD = 297, MCI = 445, controls (CTL) = 340].

Tract Based Spatial Statistic Reveals No Differences in White Matter Microstructural Organization between Carriers and Non-Carriers of the APOE ɛ4 and ɛ2 Alleles in Young Healthy Adolescents.

The apolipoprotein E (APOE) ɛ4 allele is the best established genetic risk factor for Alzheimer's disease (AD) and has been previously associated with alterations in structural gray matter and changes in functional brain activity in healthy middle-aged individuals and older non-demented subjects. In order to determine the neural mechanism by which APOE polymorphisms affect white matter (WM) structure, we investigated the diffusion characteristics of WM tracts in carriers and non-carriers of the APOE ɛ4 and ɛ2 alleles using an unbiased whole brain analysis technique (Tract Based Spatial Statistics) in a healthy young adolescent (14 years) cohort. A large sample of healthy young adolescents (n = 575) were selected from the European neuroimaging-genetics IMAGEN study with available APOE status and accompanying diffusion imaging data.

A Subset of Cerebrospinal Fluid Proteins from a Multi-Analyte Panel Associated with Brain Atrophy, Disease Classification and Prediction in Alzheimer's Disease.

In this exploratory neuroimaging-proteomic study, we aimed to identify CSF proteins associated with AD and test their prognostic ability for disease classification and MCI to AD conversion prediction. Our study sample consisted of 295 subjects with CSF multi-analyte panel data and MRI at baseline downloaded from ADNI. Firstly, we tested the statistical effects of CSF proteins (n = 83) to measures of brain atrophy, CSF biomarkers, ApoE genotype and cognitive decline.

Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes.

There is great interest in blood-based markers of Alzheimer's disease (AD), especially in its pre-symptomatic stages. Therefore, we aimed to identify plasma proteins whose levels associate with potential markers of pre-symptomatic AD. We also aimed to characterise confounding by genetics and the effect of genetics on blood proteins in general.

Aberrant cerebral network topology and mild cognitive impairment in early Parkinson's disease.

The aim of this study was to assess whether mild cognitive impairment (MCI) is associated with disruption in large-scale structural networks in newly diagnosed, drug-naïve patients with Parkinson's disease (PD). Graph theoretical analyses were applied to 3T MRI data from 123 PD patients and 56 controls from the Parkinson's progression markers initiative (PPMI). Thirty-three patients were classified as having Parkinson's disease with mild cognitive impairment (PD-MCI) using the Movement Disorders Society Task Force criteria, while the remaining 90 PD patients were classified as cognitively normal (PD-CN).

The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e.

Automated CT-based segmentation and quantification of total intracranial volume.

Objectives: To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images.

Materials And Methods: Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI).

Practical cut-offs for visual rating scales of medial temporal, frontal and posterior atrophy in Alzheimer's disease and mild cognitive impairment.

Background: Atrophy in the medial temporal lobe, frontal lobe and posterior cortex can be measured with visual rating scales such as the medial temporal atrophy (MTA), global cortical atrophy - frontal subscale (GCA-F) and posterior atrophy (PA) scales, respectively. However, practical cut-offs are urgently needed, especially now that different presentations of Alzheimer's disease (AD) are included in the revised diagnostic criteria.

Aims: The aim of this study was to generate a list of practical cut-offs for the MTA, GCA-F and PA scales, for both diagnosis of AD and determining prognosis in mild cognitive impairment (MCI), and to evaluate the influence of key demographic and clinical factors on these cut-offs.

Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease.

Introduction: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase.

Linking Genetics of Brain Changes to Alzheimer's Disease: Sparse Whole Genome Association Scan of Regional MRI Volumes in the ADNI and AddNeuroMed Cohorts.

Background: Alzheimer's disease (AD) is a highly heritable disease, but until recently few replicated genetic markers have been identified. Markers identified so far are likely to account for only a tiny fraction of the heritability of AD and many more genetic risk alleles are thought to be undiscovered.

Objective: Identifying genetic markers for AD using combined analysis of genetics and brain imaging data.

White matter changes in familial Alzheimer's disease.

Background: Familial Alzheimer's disease (FAD) resulting from gene mutations in PSEN1, PSEN2 and APP is associated with changes in the brain.

Objective: The aim of this study was to investigate changes in grey matter (GM), white matter (WM) and the cerebrospinal fluid (CSF) in FAD.

Subjects: Ten mutation carriers (MCs) with three different mutations in PSEN1 and APP and 20 noncarriers (NCs) were included in the study.

Common genetic variants influence human subcortical brain structures.

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.

Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease.

Several studies support the relation between leptin and Alzheimer's disease (AD). We show that leptin levels in CSF are unchanged as subjects progress to AD. However, in AD hippocampus, leptin signalling was decreased and leptin localization was shifted, being more abundant in reactive astrocytes and less in neurons.

Random Forest ensembles for detection and prediction of Alzheimer's disease with a good between-cohort robustness.

Computer-aided diagnosis of Alzheimer's disease (AD) is a rapidly developing field of neuroimaging with strong potential to be used in practice. In this context, assessment of models' robustness to noise and imaging protocol differences together with post-processing and tuning strategies are key tasks to be addressed in order to move towards successful clinical applications. In this study, we investigated the efficacy of Random Forest classifiers trained using different structural MRI measures, with and without neuroanatomical constraints in the detection and prediction of AD in terms of accuracy and between-cohort robustness.

Automated Hippocampal Subfield Measures as Predictors of Conversion from Mild Cognitive Impairment to Alzheimer's Disease in Two Independent Cohorts.

Previous studies have shown that hippocampal subfields may be differentially affected by Alzheimer's disease (AD). This study used an automated analysis technique and two large cohorts to (1) investigate patterns of subfield volume loss in mild cognitive impairment (MCI) and AD, (2) determine the pattern of subfield volume loss due to age, gender, education, APOE ε4 genotype, and neuropsychological test scores, (3) compare combined subfield volumes to hippocampal volume alone at discriminating between AD and healthy controls (HC), and predicting future MCI conversion to AD at 12 months. 1,069 subjects were selected from the AddNeuroMed and Alzheimer's disease neuroimaging initiative (ADNI) cohorts.

Improving CSF Biomarkers' Performance for Predicting Progression from Mild Cognitive Impairment to Alzheimer's Disease by Considering Different Confounding Factors: A Meta-Analysis.

Background: Cerebrospinal fluid (CSF) biomarkers' performance for predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is still suboptimal.

Objective: By considering several confounding factors we aimed to identify in which situations these CSF biomarkers can be useful.

Data Sources: A systematic review was conducted on MEDLINE, PreMedline, EMBASE, PsycInfo, CINAHL, Cochrane, and CRD (1990-2013).

The use of MRI, CT and lumbar puncture in dementia diagnostics: data from the SveDem Registry.

Background/aims: The use of structural brain imaging [computed tomography (CT)/magnetic resonance imaging (MRI)] and the analysis of cerebrospinal fluid biomarkers are included in the guidelines for the diagnosis of dementia. The influence of variables such as age, gender and disease severity on the use of MRI, CT and lumbar puncture (LP) for the differential diagnosis of dementia and the consonance with the recommendations of the Swedish national guidelines were investigated.

Methods: From the National Swedish Dementia Registry (SveDem), 17,057 newly diagnosed dementia patients were included in our study, with the majority from specialist care units (90%).

The effects of intracranial volume adjustment approaches on multiple regional MRI volumes in healthy aging and Alzheimer's disease.

In neurodegeneration research, normalization of regional volumes by intracranial volume (ICV) is important to estimate the extent of disease-driven atrophy. There is little agreement as to whether raw volumes, volume-to-ICV fractions or regional volumes from which the ICV factor has been regressed out should be used for volumetric brain imaging studies. Using multiple regional cortical and subcortical volumetric measures generated by Freesurfer (51 in total), the main aim of this study was to elucidate the implications of these adjustment approaches.

Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base.

The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven.

The antibiotic resistome: what's new?

The antibiotic resistome is dynamic and ever expanding, yet its foundations were laid long before the introduction of antibiotics into clinical practice. Here, we revisit our theoretical framework for the resistome concept and consider the many factors that influence the evolution of novel resistance genes, the spread of mobile resistance elements, and the ramifications of these processes for clinical practice. Observing the trends and prevalence of genes within the antibiotic resistome is key to maintaining the efficacy of antibiotics in the clinic.

The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective.

Background: Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults.

Method: In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer.