Suchergebnisse

The US military veteran population receiving care through the Veterans Health Administration (VHA) is particularly susceptible to cognitive impairment and dementias such as Alzheimer's disease and related dementias due to demographic, clinical, and economic factors. In this report we summarize the prevalence of dementia among US veterans and risks associated with AD and related dementias. We discuss the likelihood that these risks may be increasing in those about to enter the age in which dementias are common. We propose that VHA, the largest integrated health care system in the US, has shown promise in managing health risks that impact dementia prevention and propose further system wide approaches to be assessed for effective dementia prevention and care delivery.

Abstract  A major challenge to developing therapeutic interventions for cognitive loss and dementia in aging individuals with Down syndrome (DS) is the selection of appropriate outcome measures. This report describes the adaptation of the Brief Praxis Test (a nonverbal cognitive test) as a primary outcome measure, as well as the selection of secondary outcome measures for a multicenter clinical trial of vitamin E in aging individuals with DS. Instruments were chosen to assess cognition, behavior, and clinical global function based on previous work in DS and in Alzheimer's disease. Measures of cognition included verbal and nonverbal memory, vocabulary, and orientation. An informant‐based measure of behavior and function was adapted from several existing rating scales, and the Clinical Global Impression was adapted for use with this group. This report also describes initial experiences using these measures with the participants who were enrolled in the clinical trial. As in other populations of persons with dementia, verbal learning, memory, and delayed recall proved to be highly associated with the presence of dementia in our study participants. With the exception of visual memory and orientation measures (which proved too difficult to use with portions of this cohort), the tests employed proved useful in the assessment of individuals across a range of premorbid levels of intellectual disability. The authors conclude that the measures chosen for the assessment of behavior and functional ability and the use of the Clinical Global Impression appear to be appropriate for this population and comparable to instruments that have captured pharmacological benefits in other disease groups.

Abstract  Older individuals with Down syndrome have an extremely high risk of Alzheimer's disease (AD). Advances in understanding the pathophysiology of AD, and the development of effective therapies for individuals with sporadic AD, have raised the possibility that aging Down syndrome individuals may benefit from therapy directed against AD. As no prior large clinical trials had been conducted with this population, the authors launched "A Multicenter Trial of Vitamin E in Aging Individuals with Down Syndrome." The authors describe how they assembled an international group of investigators to develop the infrastructure and methodology for studying the efficacy of therapeutic interventions aimed at slowing the process of AD in Down syndrome. The process of designing and implementing the trial drew together clinical scientists and clinicians from two distinct but overlapping areas: researchers in the areas of Down syndrome and AD therapeutics. The authors review the issues considered and decisions made regarding various aspects of the trial design.

BACKGROUND: The COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs), forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19, we examined several scenarios in symptomatic and disease modification trials that could be made. METHODS: We identified both symptomatic and disease modification Alzheimer disease RCTs as exemplars of those that would be affected by the pandemic and considered the types of changes that sponsors could make to each. We modeled three scenarios for each of the types of trials using existing datasets, adjusting enrollment, follow-ups, and dropouts to examine the potential effects COVID-19-related changes. Simulations were performed that accounted for completion and dropout patterns using linear mixed effects models, modeling time as continuous and categorical. The statistical power of the scenarios was determined. RESULTS: Truncating both symptomatic and disease modification trials led to underpowered trials. By contrast, adapting the trials by extending the treatment period, temporarily stopping treatment, delaying outcomes assessments, and performing remote assessment allowed for increased statistical power nearly to the level originally planned. DISCUSSION: These analyses support the idea that disrupted trials under common scenarios are better continued and extended even in the face of dropouts, treatment disruptions, missing outcomes, and other exigencies and that adaptations can be made that maintain the trials validity. We suggest some adaptive methods to do this noting that some changes become under-powered to detect the original effect sizes and expected outcomes. These analyses provide insight to better plan trials that are resilient to unexpected changes to the medical, social, and political milieu.

BACKGROUND: The COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs), forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19, we examined several scenarios in symptomatic and disease modification trials that could be made. METHODS: We identified both symptomatic and disease modification Alzheimer disease RCTs as exemplars of those that would be affected by the pandemic and considered the types of changes that sponsors could make to each. We modeled three scenarios for each of the types of trials using existing datasets, adjusting enrollment, follow-ups, and dropouts to examine the potential effects COVID-19-related changes. Simulations were performed that accounted for completion and dropout patterns using linear mixed effects models, modeling time as continuous and categorical. The statistical power of the scenarios was determined. RESULTS: Truncating both symptomatic and disease modification trials led to underpowered trials. By contrast, adapting the trials by extending the treatment period, temporarily stopping treatment, delaying outcomes assessments, and performing remote assessment allowed for increased statistical power nearly to the level originally planned. DISCUSSION: These analyses support the idea that disrupted trials under common scenarios are better continued and extended even in the face of dropouts, treatment disruptions, missing outcomes, and other exigencies and that adaptations can be made that maintain the trials' validity. We suggest some adaptive methods to do this noting that some changes become under-powered to detect the original effect sizes and expected outcomes. These analyses provide insight to better plan trials that are resilient to unexpected changes to the medical, social, and political milieu.

The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the "A, T, N System" (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed.