XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

/pdf/nia-aa-research-framework-toward-a-biological-definition-of-1sjt6cvmd3.pdf

NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease

We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4–21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8–10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse “movies” reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.

/pdf/dynamic-mapping-of-human-cortical-development-during-4exe28dzte.pdf

Dynamic mapping of human cortical development during childhood through early adulthood

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/194901/Stockwell_Cell_review+2017.pdf

Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

The most widely used task functional magnetic resonance imaging (fMRI) analyses use parametric statistical methods that depend on a variety of assumptions. In this work, we use real resting-state data and a total of 3 million random task group analyses to compute empirical familywise error rates for the fMRI software packages SPM, FSL, and AFNI, as well as a nonparametric permutation method. For a nominal familywise error rate of 5%, the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference. Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape. By comparison, the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference. These findings speak to the need of validating the statistical methods being used in the field of neuroimaging.

https://www.pnas.org/content/pnas/113/28/7900.full.pdf

Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates

The invention provides a specific measure of iron stores in vivo using magnetic resonance imaging. T2 relaxation times in both lower-to-mid field strength magnetic resonance imaging instruments and a higher field strength instrument is evaluated. T2 obtained at the higher field strength instrument is subtracted from T2 obtained at the lower field strength instrument. This difference, T, is then correlated with a quantitative measure of the iron stores in vivo in the scanned tissue. A two-dimensional or multidimensional map of the scanned tissue is then constructed on the basis of T to visually identify different tissue types as being normal or abnormal, either through a visual determination based on gray scales or a numeric comparison based on quantitative measure. The introduction of artificial or nonbiological substances as opposed to natural ferritin, is permitted for further diagnostic use by application of this methodology.

Method for quantitatively measuring and mapping stored iron in tissue using MRI

Survey of Protocols for the Manual Segmentation of the Hippocampus: Preparatory Steps Towards a Joint EADC-ADNI Harmonized Protocol (vol 26, pg 61, 2011)

Reduced intracortical myelination in schizophrenia.

Introduction: We attempted to extend findings of a relationship between formal thought disorder and left superior temporal gyrus (STG) volume in schizophrenia by examining two indices of formal tho...

George Bartzokis

Papers

Method for quantitatively measuring and mapping stored iron in tissue using MRI

Survey of Protocols for the Manual Segmentation of the Hippocampus: Preparatory Steps Towards a Joint EADC-ADNI Harmonized Protocol (vol 26, pg 61, 2011)

Reduced intracortical myelination in schizophrenia.

Neuroanatomical correlates of formal thought disorder in schizophrenia.

Mood-state effects on amygdala volume in bipolar disorder.