Quantification of white matter cellularity and damage in preclinical and early symptomatic Alzheimer\u27s disease

Interest in understanding the roles of white matter (WM) inflammation and damage in the pathophysiology of Alzheimer disease (AD) has been growing significantly in recent years. However, in vivo magnetic resonance imaging (MRI) techniques for imaging inflammation are still lacking. An advanced diffusion-based MRI method, neuro-inflammation imaging (NII), has been developed to clinically image and quantify WM inflammation and damage in AD. Here, we employed NII measures in conjunction with cerebrospinal fluid (CSF) biomarker classification (for β-amyloid (Aβ) and neurodegeneration) to evaluate 200 participants in an ongoing study of memory and aging. Elevated NII-derived cellular diffusivity was observed in both preclinical and early symptomatic phases of AD, while disruption of WM integrity, as detected by decreased fractional anisotropy (FA) and increased radial diffusivity (RD), was only observed in the symptomatic phase of AD. This may suggest that WM inflammation occurs earlier than WM damage following abnormal Aβ accumulation in AD. The negative correlation between NII-derived cellular diffusivity and CSF Aβ42 level (a marker of amyloidosis) may indicate that WM inflammation is associated with increasing Aβ burden. NII-derived FA also negatively correlated with CSF t-tau level (a marker of neurodegeneration), suggesting that disruption of WM integrity is associated with increasing neurodegeneration. Our findings demonstrated the capability of NII to simultaneously image and quantify WM cellularity changes and damage in preclinical and early symptomatic AD. NII may serve as a clinically feasible imaging tool to study the individual and composite roles of WM inflammation and damage in AD. Keywords: Inflammation, White matter damage, Diffusion basis spectrum imaging, Neuro-inflammation imaging, Cerebrospinal fluid, Preclinical Alzheimer disease, Early symptomatic Alzheimer disease, Magnetic resonance imagin

Longitudinal Cerebrospinal Fluid Biomarkers of Alzheimer Disease: Movement Toward the Diagnosis, Prognosis and Staging of Disease

Alzheimer’s disease (AD) is a devastating neurodegenerative disease that slowly claims the memories and experiences that comprise the life experiences of individuals that suffer from the disease. Despite a continually accelerating pace of research and discovery, a viable therapeutic intervention for AD has yet to be realized. There are a multitude of factors that may contribute to this difficulty including the challenge of separating the overall disease of Alzheimer’s from the clinically recognizable memory loss that occurs in what is now known to be the end-stage of the disease. Efforts to treat AD have increasingly turned toward very early disease states, before clinical signs and symptoms become apparent, as a number of clinical trials have failed to meet cognitive endpoints over the last 5-10 years – potentially due to the sole recruitment of individuals already experiencing significant cognitive decline. One important aspect of AD treatment is identification. It is now recognized that the disease begins more than a decade before the signature symptoms of cognitive impairment become apparent. Identifying individuals in this “preclinical” disease state has become a primary focus of many investigators who believe that AD must be targeted and fought well before the clinical manifestations of memory impairment appear. Biomarkers, indicators of normal biological or pathological processes that may be studied as a means to give individuals a disease diagnosis, prognosis, or theragnosis – provided a treatment is available for the disease in question – are of paramount importance in many diseases. AD has proved a difficult target to nail down reliable, sensitive, and specific biomarkers. This is in part due to analytical difficulties in major, core biomarkers of disease and in part due to setbacks in clinical trials of promising therapeutic candidates. The current work begins with an overview of biomarker modalities used in AD; however, the primary focus is on protein biomarkers in cerebrospinal fluid (CSF). CSF provides an intimate window to the central nervous system that, in the case of AD, has shown the ability to identify and monitor disease progress over time in cohorts of cognitively normal and demented individuals. In an effort to pinpoint AD before clinical signs and symptoms manifest, biomarker research in preclinical AD has become a robust area of investigation. CSF biomarkers of amyloid pathology, neuronal damage, and neuroinflammation are discussed in two independent cohorts: the Adult Children Study (ACS) from Washington University in St. Louis and the Alzheimer’s Disease Neuroimaging Initiative. The ACS cohort is comprised of middle-aged, cognitively normal individuals recruited on a volunteer basis from community dwelling participants with and without a family history of AD. The ADNI cohort is comprised of older individuals also recruited on a volunteer basis from community dwelling participants, though participants are recruited with respect to clinical status and include cognitively normal individuals, individuals with mild cognitive impairment, and individuals with AD, in addition to being older than the ACS cohort. In both cohorts, it was found that CSF markers of amyloid plaques – one of two required pathological hallmarks that indicate AD – changed earlier than those of tau tangles, the second required pathological hallmark. Currently, examining biomarkers on a group-wide basis is the best way to get an accurate picture of biomarkers at baseline and followup lumbar punctures (LPs). As the goal is to be able to give individual people a diagnosis and prognosis of their disease, the behavior of biomarkers is particularly interesting because studies have found that CSF Aβ42 changes up to 15 or more years before cognitive signs and symptoms become apparent and, hopefully, beginning treatment in this period will be helpful not only for diagnosing for individuals with AD dementia, but also for individuals with very early disease

Patient-powered research networks: building capacity for conducting patient-centered clinical outcomes research.

The Patient-Centered Outcomes Research Institute (PCORI) recently launched PCORnet to establish a single inter-operable multicenter data research network that will support observational research and randomized clinical trials. This paper provides an overview of the patient-powered research networks (PPRNs), networks of patient organizations focused on a particular health condition that are interested in sharing health information and engaging in research. PPRNs will build on their foundation of trust within the patient communities and draw on their expertise, working with participants to identify true patient-centered outcomes and direct a patient-centered research agenda. The PPRNs will overcome common challenges including enrolling a diverse and representative patient population; engaging patients in governance; designing the data infrastructure; sharing data securely while protecting privacy; prioritizing research questions; scaling small networks into a larger network; and identifying pathways to sustainability. PCORnet will be the first distributed research network to bring PCOR to national scale

The Building Blocks of Interoperability. A Multisite Analysis of Patient Demographic Attributes Available for Matching.

BackgroundPatient matching is a key barrier to achieving interoperability. Patient demographic elements must be consistently collected over time and region to be valuable elements for patient matching.ObjectivesWe sought to determine what patient demographic attributes are collected at multiple institutions in the United States and see how their availability changes over time and across clinical sites.MethodsWe compiled a list of 36 demographic elements that stakeholders previously identified as essential patient demographic attributes that should be collected for the purpose of linking patient records. We studied a convenience sample of 9 health care systems from geographically distinct sites around the country. We identified changes in the availability of individual patient demographic attributes over time and across clinical sites.ResultsSeveral attributes were consistently available over the study period (2005-2014) including last name (99.96%), first name (99.95%), date of birth (98.82%), gender/sex (99.73%), postal code (94.71%), and full street address (94.65%). Other attributes changed significantly from 2005-2014: Social security number (SSN) availability declined from 83.3% to 50.44% (p<0.0001). Email address availability increased from 8.94% up to 54% availability (p<0.0001). Work phone number increased from 20.61% to 52.33% (p<0.0001).ConclusionsOverall, first name, last name, date of birth, gender/sex and address were widely collected across institutional sites and over time. Availability of emerging attributes such as email and phone numbers are increasing while SSN use is declining. Understanding the relative availability of patient attributes can inform strategies for optimal matching in healthcare

Coil and Halt

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The Denison Pequotsepos Nature Center Giving Garden at Coogan Farm: A Practitioner Report on Community Gardens for Health and Regional Food Security

The Denison Pequotsepos Nature Center (DPNC) is a community organization that, through its various programming, works to perpetuate a vision of humans as part and parcel of the world. In 2013, when the Nature Center acquired the Coogan Farm property, the organization built a community garden called the Giving Garden to serve surrounding communities, expanding services to the foodservice sector educational programming around sustainable agriculture. DPNC’s partnership with the Robert G. Youngs Family Foundation, United Way of Southeastern Connecticut, and Gemma E. Moran mobile food pantry, forged in 2014, has allowed the garden to minimize area food insecurity through its contribution of seasonal fruits and vegetables farmed through biointensive, regenerative agricultural practices. This report integrates a participatory research approach, reflecting on my time spent as an intern in the garden in summer 2017 and, now, on my position as the Assistant Garden Manager in the Coogan Farm Giving Garden. Major studies indicate the positive effects that community gardens can have on minimizing regional food insecurity, creating cohesive communities, and increasing overall health of residents. The purpose of this study is to investigate and convey the impact that community gardens have on community health and regional food security in New London County, Connecticut, using the Giving Garden as a case study. Findings suggest that members of the Giving Garden experience a heightened sense of community, recipients of garden outputs achieve greater overall health, and that educational programs teaching the importance of sustainable farming practices over conventional agriculture promote household farming and gardening practices that are more ecologically friendly on a community level

After Visiting the Oracle

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The Failure of the Fast Deployment Logistics Ship

To the Secretary of Defense, Fast Deployment Logistics ships (FDL\u27s) were an essential component of a strategic capability for rapid military response, but to a labor leader they were McNamara\u27s floating Edsels and super juggernauts of the sea.