Molly V. Wagster

Bio: Molly V. Wagster is an academic researcher from National Institutes of Health. The author has contributed to research in topics: NIH Toolbox & Cognition. The author has an hindex of 11, co-authored 16 publications receiving 6513 citations.

Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Abstract: The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.

NIH Toolbox for Assessment of Neurological and Behavioral Function

Abstract: At present, there are many studies that collect information on aspects of neurologic and behavioral function (cognition, sensation, movement, emotion), but with little uniformity among the measures used to capture these constructs. Further, available measures are generally expensive, normed on homogenous nondiverse populations, not easily administered, do not cover the lifespan (or have easily linked pediatric and adult counterparts for the purposes of longitudinal comparison), and not based on the current thinking in the neuroscience community. There is also a paucity of measurement tools to gauge normal children in the motor and sensation domain areas, and many of these measures rely heavily on proxy reporting. Investigators have expressed the need for brief assessment tools that could address these issues and be used as a form of "common currency" across diverse study designs and populations. This ability to assess functionality along a common metric and "crosswalk" across measures is essential to the process of being able to pool data, which is often necessary when a large and diverse sample is needed. When individual studies employ unique assessment batteries, comparisons between studies and combining data from multiple studies can be problematic. The contract for the NIH Toolbox for the Assessment of Neurological and Behavioral Function (www.nihtoolbox.org) was initiated by the NIH Blueprint for Neuroscience Research (www.neuroscienceblueprint.nih.gov) to develop a set of state-of-the-art measurement tools to enhance collection of data in large cohort studies and to advance the biomedical research enterprise.

Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup

Abstract: The pathophysiological process of Alzheimer’s disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long “preclinical” phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer’s Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from “normal” cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommen

The NIH Cognitive and Emotional Health Project

Abstract: Background The Cognitive and Emotional Health Project (CEHP) seeks to identify the demographic, social, and biological determinants of cognitive and emotional health in the older adult. As part of the CEHP, a critical evaluation study committee was formed to assess the state of epidemiological research on demographic, social, and biological determinants of cognitive and emotional health. Methods Criteria for inclusion in the survey were large cohort studies, longitudinal in design, participants predominantly 65 years or older, with measurements of both cognition and emotion, and information on a wide variety of demographic, psychosocial, and biological factors. North American and European studies, which met these criteria, were selected for the review. Outcome measures included cognition, cognitive decline, and cognitive function. For emotion, symptoms included depression and anxiety, positive and negative affect, subjective well being, mastery, and resilience. Results Ninety-six papers were identified that addressed cognitive and emotional outcomes. A large variety of risk factors were consistently identified with cognitive outcomes, particularly those previously associated with increased risk of cardiovascular disease. There was considerable overlap between risk factors for cognitive and emotional outcomes. Conclusion This review identifies a large number of lifestyle and health behaviors that alter the risk for maintenance of cognitive and emotional health. Large longitudinal cohort studies are a unique source to explore factors associated with cognitive and emotional health. Secondary analyses of these studies should be encouraged as should the development of standardized questionnaires to measure cognitive and emotional health. Future research in this field should study cognitive and emotional health simultaneously.

The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease

Abstract: The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

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

Abstract: 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.

2013 Alzheimer's disease facts and figures

Abstract: This report provides information to increase understanding of the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, health expenditures and costs of care, and effect on caregivers and society in general. It also explores the roles and unique challenges of long‐distance caregivers, as well as interventions that target those challenges. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million comprise the older onset AD population. Throughout the coming decades, the baby boom generation is projected to add about 10 million to the total number of people in the United States with AD. Today, someone in America develops AD every 68 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. AD is the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The number of deaths from AD as determined by official death certificates (83,494 in 2010) likely underrepresents the number of AD‐related deaths in the United States. A projected 450,000 older Americans with AD will die in 2013, and a large proportion will die as a result of complications of AD. In 2012, more than 15 million family members and other unpaid caregivers provided an estimated 17.5 billion hours of care to people with AD and other dementias, a contribution valued at more than $216 billion. Medicare payments for services to beneficiaries age 65 years and older with AD and other dementias are three times as great as payments for beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2013 for health care, long‐term care, and hospice services for people age 65 years and older with dementia are expected to be $203 billion (not including the contributions of unpaid caregivers). An estimated 2.3 million caregivers of people with AD and other dementias live at least 1 hour away from the care recipient. These “long‐distance caregivers” face unique challenges, including difficulty in assessing the care recipient's true health condition and needs, high rates of family disagreement regarding caregiving decisions, and high out‐of‐pocket expenses for costs related to caregiving. Out‐of‐pocket costs for long‐distance caregivers are almost twice as high as for local caregivers.

Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease

Abstract: A B S T R AC T BACKGROUND The order and magnitude of pathologic processes in Alzheimer’s disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer’s disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant’s age at baseline assessment and the parent’s age at the onset of symptoms of Alzheimer’s disease to calculate the estimated years from expected symptom onset (age of the participant minus parent’s age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. RESULTS Concentrations of amyloid-beta (Aβ)42 in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini–Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. CONCLUSIONS We found that autosomal dominant Alzheimer’s disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer’s disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer’s disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)