Dementia Risk in Posttraumatic Stress Disorder: the Relevance of Sleep-Related Abnormalities in Brain Structure, Amyloid, and Inflammation.

Purpose Of Review: Posttraumatic stress disorder (PTSD) is associated with increased risk for dementia, yet mechanisms are poorly understood.

Recent Findings: Recent literature suggests several potential mechanisms by which sleep impairments might contribute to the increased risk of dementia observed in PTSD. First, molecular, animal, and imaging studies indicate that sleep problems lead to cellular damage in brain structures crucial to learning and memory.

A critical appraisal of guidelines for electronic communication between patients and clinicians: the need to modernize current recommendations.

Background: Patient-provider electronic communication has proliferated in recent years, yet there is a dearth of published research either leading to, or including, recommendations that improve clinical care and prevent unintended negative consequences. We critically appraise published guidelines and suggest an agenda for future work in this area.

Objective: To understand how existing guidelines align with current practice, evidence, and technology.

Traumatic brain injury may not increase the risk of Alzheimer disease.

Traumatic brain injury (TBI) commonly occurs in civilian and military populations. Some epidemiologic studies previously have associated TBI with an increased risk of Alzheimer disease (AD). Recent clinicopathologic and biomarker studies have failed to confirm the relationship of TBI to the development of AD dementia or pathologic changes, and suggest that other neurodegenerative processes might be linked to TBI.

Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) patients display hippocampal atrophy, memory impairment, and cognitive decline. New neurons are generated throughout adulthood in 2 regions of the brain implicated in AD, the dentate gyrus of the hippocampus and the subventricular zone of the olfactory bulb. Disruption of this process contributes to neurodegenerative diseases including AD, and many of the molecular players in AD are also modulators of adult neurogenesis.

Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary Report.

Introduction: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD.

Methods: Potential subjects identified by Veterans Administration records underwent an initial telephone screen.

Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study.

Introduction: Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials.

Methods: Serial T1-weighted magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point.

Systematic Heuristic Evaluation of Computerized Consultation Order Templates: Clinicians' and Human Factors Engineers' Perspectives.

We assessed the usability of consultation order templates and identified problems to prioritize in design efforts for improving referral communication. With a sample of 26 consultation order templates, three evaluators performed a usability heuristic evaluation. The evaluation used 14 domain-independent heuristics and the following three supplemental references: 1 new domain-specific heuristic, 6 usability goals, and coded clinicians' statements regarding ease of use for 10 sampled templates.

Cortical Atrophy is Associated with Accelerated Cognitive Decline in Mild Cognitive Impairment with Subsyndromal Depression.

Objectives: To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period.

Design: Prospective cohort study.

Setting: Multicenter, clinic-based.

Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons.

Importance: Among cognitively normal individuals, elevated brain amyloid (defined by cerebrospinal fluid assays or positron emission tomography regional summaries) can be related to risk for later Alzheimer-related cognitive decline.

Objective: To characterize and quantify the risk for Alzheimer-related cognitive decline among cognitively normal individuals with elevated brain amyloid.

Design, Setting, And Participants: Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal individuals in the United States and Canada.

Triglycerides are negatively correlated with cognitive function in nondemented aging adults.

Objective: Vascular risk factors like hyperlipidemia may adversely affect brain function. We hypothesized that increased serum triglycerides are associated with decreased executive function and memory in nondemented elderly subjects. We also researched possible vascular mediators and white matter microstructure as assessed with diffusion tensor imaging (DTI).

Association analysis of rare variants near the APOE region with CSF and neuroimaging biomarkers of Alzheimer's disease.

Background: The APOE ε4 allele is the most significant common genetic risk factor for late-onset Alzheimer's disease (LOAD). The region surrounding APOE on chromosome 19 has also shown consistent association with LOAD. However, no common variants in the region remain significant after adjusting for APOE genotype.

Time to Amyloid Positivity and Preclinical Changes in Brain Metabolism, Atrophy, and Cognition: Evidence for Emerging Amyloid Pathology in Alzheimer's Disease.

Aβ pathology is associated with longitudinal changes of brain metabolism, atrophy, and cognition, in cognitively healthy elders. However, Aβ information is usually measured cross-sectionally and dichotomized to classify subjects as Aβ-positive or Aβ-negative, making it difficult to evaluate when brain and cognitive changes occur with respect to emerging Aβ pathology. In this study, we use longitudinal Aβ information to combine the level and rate of change of Aβ to estimate the time to Aβ-positivity for each subject and test this temporal proximity to significant Aβ pathology for associations with brain structure, metabolism, and cognition.

Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease.

Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study.

Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis.

Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer's disease.

Introduction: The objective of this study was to evaluate the relationship between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers.

Methods: In 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self-reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ and CSF tau levels was evaluated using linear regression.

Results: No differences in brain amyloid load, CSF Aβ, or CSF tau were observed between low and high exercise groups.

Adapting Cognitive Task Analysis to Investigate Clinical Decision Making and Medication Safety Incidents.

Objectives: Cognitive task analysis (CTA) can yield valuable insights into healthcare professionals' cognition and inform system design to promote safe, quality care. Our objective was to adapt CTA-the critical decision method, specifically-to investigate patient safety incidents, overcome barriers to implementing this method, and facilitate more widespread use of cognitive task analysis in healthcare.

Methods: We adapted CTA to facilitate recruitment of healthcare professionals and developed a data collection tool to capture incidents as they occurred.

Long-term Health-related Quality of Life Outcomes Following Radical Cystectomy.

Objective: To evaluate the long-term (>5 years) health-related quality of life (HRQOL) outcomes following radical cystectomy, comparing Indiana pouch (IP), neobladder (NB), and ileal conduit (IC).

Materials And Methods: The departmental radical cystectomy database was queried to identify patients who underwent radical cystectomy and urinary diversion for bladder cancer between 1991 and 2009 and had not died. Three hundred patients were identified and sent the validated Bladder Cancer Index instrument.

Data-driven regions of interest for longitudinal change in three variants of frontotemporal lobar degeneration.

Introduction: Longitudinal imaging of neurodegenerative disorders is a potentially powerful biomarker for use in clinical trials. In Alzheimer's disease, studies have demonstrated that empirically derived regions of interest (ROIs) can provide more reliable measurement of disease progression compared with anatomically defined ROIs.

Methods: We set out to derive ROIs with optimal effect size for quantifying longitudinal change in a hypothetical clinical trial by comparing atrophy rates in 44 patients with behavioral variant of frontotemporal dementia (bvFTD), 30 with the semantic variant primary progressive aphasia (svPPA), and 26 with the nonfluent variant PPA (nfvPPA) to atrophy in 97 cognitively healthy controls.

Line Tension Controls Liquid-Disordered + Liquid-Ordered Domain Size Transition in Lipid Bilayers.

To better understand animal cell plasma membranes, we studied simplified models, namely four-component lipid bilayer mixtures. Here we describe the domain size transition in the region of coexisting liquid-disordered (Ld) + liquid-ordered (Lo) phases. This transition occurs abruptly in composition space with domains increasing in size by two orders of magnitude, from tens of nanometers to microns.

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

Background: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline.

Methods: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco.

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials.

Introduction: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015.

Methods: We used standard searches to find publications using ADNI data.

Metabolic network failures in Alzheimer's disease: A biochemical road map.

Introduction: The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance.

Association between tau deposition and antecedent amyloid-β accumulation rates in normal and early symptomatic individuals.

See Vandenberghe and Schaeverbeke (doi:10.1093/awx065) for a scientific commentary on this article. A long-term goal of our field is to determine the sequence of pathological events, which ultimately lead to cognitive decline and dementia.

Medication Use among Veterans across Health Care Systems.

Introduction: Dual healthcare system use can create gaps and fragments of information for patient care. The Department of Veteran Affairs is implementing a health information exchange (HIE) program called the Virtual Lifetime Electronic Record (VLER), which allows providers to access and share information across healthcare systems. HIE has the potential to improve the safety of medication use.

Fractional anisotropy derived from the diffusion tensor distribution function boosts power to detect Alzheimer's disease deficits.

Purpose: In diffusion MRI (dMRI), fractional anisotropy derived from the single-tensor model (FA ) is the most widely used metric to characterize white matter (WM) microarchitecture, despite known limitations in regions with crossing fibers. Due to time constraints when scanning patients in clinical settings, high angular resolution diffusion imaging acquisition protocols, often used to overcome these limitations, are still rare in clinical population studies. However, the tensor distribution function (TDF) may be used to model multiple underlying fibers by representing the diffusion profile as a probabilistic mixture of tensors.

A T1 and DTI fused 3D corpus callosum analysis in MCI subjects with high and low cardiovascular risk profile.

Understanding the extent to which vascular disease and its risk factors are associated with prodromal dementia, notably Alzheimer's disease (AD), may enhance predictive accuracy as well as guide early interventions. One promising avenue to determine this relationship consists of looking for reliable and sensitive imaging methods capable of characterizing the subtle brain alterations before the clinical manifestations. However, little is known from the imaging perspective about how risk factors such as vascular disease influence AD progression.