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.
Abstract Positron emission tomography (PET) of brain amyloid β is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. To provide ...guidance to dementia care practitioners, patients, and caregivers, the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific appropriate use criteria (AUC) were agreed on that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes.
A new secondary prevention trial in older people with amyloid accumulation at high risk for Alzheimer's disease dementia should provide insights into whether anti-amyloid therapy can delay cognitive ...decline.
Positron emission tomography (PET) of brain amyloid β is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. To provide guidance to ...dementia care practitioners, patients, and caregivers, the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific appropriate use criteria (AUC) were agreed on that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes.
Despite long-standing critiques of the conduct of underpowered clinical
trials, the practice not only remains widespread, but also has garnered increasing
support. Patients and healthy volunteers ...continue to participate in research
that may be of limited clinical value, and authors recently have offered 2
related arguments to support the validity and value of underpowered clinical
trials: that meta-analysis may "save" small studies by providing a means to
combine the results with those of other similar studies to enable estimates
of an intervention's efficacy, and that although small studies may not provide
a good basis for testing hypotheses, they may provide valuable estimates of
treatment effects using confidence intervals. In this article, we examine
these arguments in light of the distinctive moral issues associated with the
conduct of underpowered trials, the disclosures that are owed to potential
participants in underpowered trials so they may make autonomous enrollment
decisions, and the circumstances in which the prospects for future meta-analyses
may justify individually underpowered trials. We conclude that underpowered
trials are ethical in only 2 situations: small trials of interventions for
rare diseases in which investigators document explicit plans for including
their results with those of similar trials in a prospective meta-analysis,
and early-phase trials in the development of drugs or devices, provided they
are adequately powered for defined purposes other than randomized treatment
comparisons. In both cases, investigators must inform prospective subjects
that their participation may only indirectly contribute to future health care
benefits.
Background In the context of an aging end-stage renal disease population with multiple comorbid conditions, transplantation professionals face challenges in evaluating the global health of patients ...awaiting kidney transplantation. Functional status might be useful for identifying which patients will derive a survival benefit from transplantation versus dialysis. Study Design Retrospective cohort study of wait-listed patients using data for functional status from a national dialysis provider linked to United Network for Organ Sharing registry data. Setting & Participants Adult kidney transplantation candidates added to the waiting list between 2000 and 2006. Predictor Physical Functioning scale of the Medical Outcomes Study 36-Item Short Form Health Survey, analyzed as a time-varying covariate. Outcomes Kidney transplantation; survival benefit of transplantation versus remaining wait-listed. Measurements We used multivariable Cox regression to assess the association between physical function with study outcomes. In survival benefit analyses, transplantation status was modeled as a time-varying covariate. Results The cohort comprised 19,242 kidney transplantation candidates (median age, 51 years; 36% black race) receiving maintenance dialysis. Candidates in the lowest baseline Physical Functioning score quartile were more likely to be inactivated (adjusted HR vs highest quartile, 1.30; 95% CI, 1.21-1.39) and less likely to undergo transplantation (adjusted HR vs highest quartile, 0.64; 95% CI, 0.61-0.68). After transplantation, worse Physical Functioning score was associated with shorter 3-year survival (84% vs 92% for the lowest vs highest function quartiles). However, compared to dialysis, transplantation was associated with a statistically significant survival benefit by 9 months for patients in every function quartile. Limitations Functional status is self-reported. Conclusions Even patients with low function appear to live longer with kidney transplantation versus dialysis. For wait-listed patients, global health measures such as functional status may be more useful in counseling patients about the probability of transplantation than in identifying who will derive a survival benefit from it.
The classification of Alzheimer's disease is undergoing a significant transformation. Researchers have created the category of “preclinical Alzheimer's,” characterized by biomarker pathology rather ...than observable symptoms. Diagnosis and treatment at this stage could allow preventing Alzheimer's cognitive decline. While many commentators have worried that persons given a preclinical Alzheimer's label will be subject to stigma, little research exists to inform whether the stigma attached to the label of clinical Alzheimer's will extend to a preclinical disorder that has the label of “Alzheimer's” but lacks the symptoms or expected prognosis of the clinical form.
The present study sought to correct this gap by examining the foundations of stigma directed at Alzheimer's. It asked: do people form stigmatizing reactions to the label “Alzheimer's disease” itself or to the condition's observable impairments? How does the condition's prognosis modify these reactions?
Data were collected through a web-based experiment with N = 789 adult members of the U.S. general population (median age = 49, interquartile range, 32–60, range = 18–90). Participants were randomized through a 3 × 3 design to read one of 9 vignettes depicting signs and symptoms of mild stage dementia that varied the disease label (“Alzheimer's” vs. “traumatic brain injury” vs. no label) and prognosis (improve vs. static vs. worsen symptoms). Four stigma outcomes were assessed: discrimination, negative cognitive attributions, negative emotions, and social distance.
The study found that the Alzheimer's disease label was generally not associated with more stigmatizing reactions. In contrast, expecting the symptoms to get worse, regardless of which disease label those symptoms received, resulted in higher levels of perceived structural discrimination, higher pity, and greater social distance.
These findings suggest that stigma surrounding pre-clinical Alzheimer's categories will depend highly on the expected prognosis attached to the label. They also highlight the need for models of Alzheimer's-directed stigma that incorporate attributions about the condition's mutability.
•One of the first experimental studies of sources of Alzheimer's (AD) stigma.•Expecting symptoms to get worse resulted in more stigmatizing reactions.•The Alzheimer's label had little independent effect on increasing stigma.•Highlights implications of cultural framing of AD that focuses on most severe stages.
Desktop Medicine Karlawish, Jason
JAMA : the journal of the American Medical Association,
11/2010, Letnik:
304, Številka:
18
Journal Article
Recenzirano
The author discusses the concept, meaning and benefits of desktop medicine, a term explaining the transformation taking place in medical science via desk with networked computer. The analyses ...demonstrate the significance of training of physicians for adopting desktop medicine concept in their practices.
Clinical guidelines currently recommend against amyloid imaging for cognitively unimpaired persons. The goal of Alzheimer's disease (AD) prevention, together with advances in understanding the ...pathophysiology of AD, however, has led to trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Assuming the eventual success of such trials, millions of patients will be affected. There is a need to understand the effects of biomarker disclosure on those individuals.
The Study of Knowledge and Reactions to Amyloid Testing (SOKRATES) involved 2 semi-structured telephone interviews with individuals who received amyloid PET scan results as part of screening for research participation. Post-disclosure interviews were conducted at 4 to 12 weeks and again 1 year later. Data were collected from November 5, 2014 to November 30, 2016. Interviews were transcribed and coded in NVivo 12.0.
80 adults aged 65 and older: 50 who received "elevated" and 30 who received "not-elevated" amyloid PET scan results.
Interviews examined four domains: (1) comprehension of the amyloid PET scan result; (2) implications of the result for sense of self, memory, and future; (3) sharing of results with others; and (4) AD risk-reduction behaviors.
Participants who received an elevated amyloid PET scan result viewed the result as more serious and sensitive than other medical test results given its unique implications for identity, self-determination, and stigma. In contrast, participants who received a not-elevated amyloid PET scan result described feeling relief and reinterpreted perceived memory impairments as normal aging. Participants with elevated amyloid reported contemplating and making more changes to health behaviors and future plans than their peers with not-elevated amyloid.
Clinical practice in the diagnosis and treatment of persons with preclinical AD, a stage of the disease defined by the presence of biomarkers in the absence of cognitive impairment, will need to address matters of identity, stigma, and life-planning.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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