Identification Of Life Course Gene Environment Interactions In Cognitive Decline During The Preclinical Stage Of Alzheimer S

The etiology of Alzheimer's disease is multifaceted, involving a complex interplay of environmental and genetic factors. APOE [epislon]4 has been identified as the strongest genetic risk factor for Alzheimer's. Recent genome-wide association studies have also identified many non-APOE genetic variants that significantly contribute to Alzheimer's risk. Since these non-APOE variants typically have small effects, researchers often prefer to use a polygenic risk score to create a more robust predictor by combining the effects of these variants. However, the roles of APOE and non-APOE polygenic risk score in the disease's etiology, particularly during the preclinical stage of Alzheimer's, and whether different environmental exposures throughout life can modify the predisposed risk from APOE and non-APOE polygenic risk score, remain largely unknown. In this study, leveraging two longitudinal studies, we comprehensively evaluate how APOE, non-APOE polygenic risk score, and various environmental factors throughout life individually and jointly affect an individual's risk of Alzheimer's. We found that the effect of non-APOE polygenic risk score is particularly strong among APOE [epislon]4 carriers. Additionally, we observed that maintaining healthier lifestyles in mid-to-late life, or having an advantaged childhood socioeconomic status, can mitigate the adverse genetic effects of non-APOE polygenic risk score on later-life cognitive decline, especially among APOE [epislon]4 carriers. The findings from this research can serve as a foundation for future clinical trials and provide evidence for policymakers in designing effective policy interventions to address health disparities in Alzheimer's.

Along with psychopathology, cognition has been one of the primary phenotypic focal points of the field of behavior genetics since its inception. Francis Galton’s 1874 examination of eminent families in Britain was among the earliest attempts to investigate whether cognitive achievements run in families. This volume presents current methodologies for understanding cognitive abilities that move beyond the outdated nature vs. nurture paradigm. Recent advances in both collection and statistical modeling of twin data, particularly longitudinal twin data, make this an especially advantageous moment to produce a work that presents a collection of the groundbreaking research on cognitive abilities across the lifespan. This volume presents an overview of the current state of quantitative and molecular genetic investigations into the many facets of cognitive performance and functioning across the lifespan.​

Almost 25 years have passed since the Demography of Aging (1994) was published by the National Research Council. Future Directions for the Demography of Aging is, in many ways, the successor to that original volume. The Division of Behavioral and Social Research at the National Institute on Aging (NIA) asked the National Academies of Sciences, Engineering, and Medicine to produce an authoritative guide to new directions in demography of aging. The papers published in this report were originally presented and discussed at a public workshop held in Washington, D.C., August 17-18, 2017. The workshop discussion made evident that major new advances had been made in the last two decades, but also that new trends and research directions have emerged that call for innovative conceptual, design, and measurement approaches. The report reviews these recent trends and also discusses future directions for research on a range of topics that are central to current research in the demography of aging. Looking back over the past two decades of demography of aging research shows remarkable advances in our understanding of the health and well-being of the older population. Equally exciting is that this report sets the stage for the next two decades of innovative researchâ€"a period of rapid growth in the older American population.

For most Americans, staying "mentally sharp" as they age is a very high priority. Declines in memory and decision-making abilities may trigger fears of Alzheimer's disease or other neurodegenerative diseases. However, cognitive aging is a natural process that can have both positive and negative effects on cognitive function in older adults - effects that vary widely among individuals. At this point in time, when the older population is rapidly growing in the United States and across the globe, it is important to examine what is known about cognitive aging and to identify and promote actions that individuals, organizations, communities, and society can take to help older adults maintain and improve their cognitive health. Cognitive Aging assesses the public health dimensions of cognitive aging with an emphasis on definitions and terminology, epidemiology and surveillance, prevention and intervention, education of health professionals, and public awareness and education. This report makes specific recommendations for individuals to reduce the risks of cognitive decline with aging. Aging is inevitable, but there are actions that can be taken by individuals, families, communities, and society that may help to prevent or ameliorate the impact of aging on the brain, understand more about its impact, and help older adults live more fully and independent lives. Cognitive aging is not just an individual or a family or a health care system challenge. It is an issue that affects the fabric of society and requires actions by many and varied stakeholders. Cognitive Aging offers clear steps that individuals, families, communities, health care providers and systems, financial organizations, community groups, public health agencies, and others can take to promote cognitive health and to help older adults live fuller and more independent lives. Ultimately, this report calls for a societal commitment to cognitive aging as a public health issue that requires prompt action across many sectors.

This volume of the Subcellular Biochemistry series is the result of the long-standing research interest of the editor in the molecular mechanism underlying Alzheimer’s disease and other amyloid diseases, indicated also by the earlier book in the series (Volume 38), devoted to Alzheimer’s disease. The broad coverage within the present amyloidogenesis book represents an attempt to collate current knowledge relating to the proteins and peptides involved in most of the known amyloid diseases, together with some amyloid/fibril-forming proteins and peptides that are not involved in diseases. Thus, the range of topics included is comprehensive and furthermore it was thought appropriate to include both basic science and clinical presentation of the subjects under discussion.

This volume contains the proceedings of the 14th Colloque Médecine et Recherche of the Fondation Ipsen pour la Recherche Thérapeutique devoted to Alzheimer's Disease and dedicated to the epidemiological study of this dementia, a very important issue because the incidence and prevalence of Alzheimer's Disease rise exponentially with age. Epidemiological findings not only confirm dementia as a major challenge for the coming years but also contribute defining risk factors, predicting and may be preventing this disease.

As the largest generation in U.S. history - the population born in the two decades immediately following World War II - enters the age of risk for cognitive impairment, growing numbers of people will experience dementia (including Alzheimer's disease and related dementias). By one estimate, nearly 14 million people in the United States will be living with dementia by 2060. Like other hardships, the experience of living with dementia can bring unexpected moments of intimacy, growth, and compassion, but these diseases also affect people's capacity to work and carry out other activities and alter their relationships with loved ones, friends, and coworkers. Those who live with and care for individuals experiencing these diseases face challenges that include physical and emotional stress, difficult changes and losses in their relationships with life partners, loss of income, and interrupted connections to other activities and friends. From a societal perspective, these diseases place substantial demands on communities and on the institutions and government entities that support people living with dementia and their families, including the health care system, the providers of direct care, and others. Nevertheless, research in the social and behavioral sciences points to possibilities for preventing or slowing the development of dementia and for substantially reducing its social and economic impacts. At the request of the National Institute on Aging of the U.S. Department of Health and Human Services, Reducing the Impact of Dementia in America assesses the contributions of research in the social and behavioral sciences and identifies a research agenda for the coming decade. This report offers a blueprint for the next decade of behavioral and social science research to reduce the negative impact of dementia for America's diverse population. Reducing the Impact of Dementia in America calls for research that addresses the causes and solutions for disparities in both developing dementia and receiving adequate treatment and support. It calls for research that sets goals meaningful not just for scientists but for people living with dementia and those who support them as well. By 2030, an estimated 8.5 million Americans will have Alzheimer's disease and many more will have other forms of dementia. Through identifying priorities social and behavioral science research and recommending ways in which they can be pursued in a coordinated fashion, Reducing the Impact of Dementia in America will help produce research that improves the lives of all those affected by dementia.

Major neurocognitive disorders are one of the leading causes of disability and dependency among the elderly worldwide. Notably, their far-reaching impact extends beyond the estimated 50 million people currently living with a major neurocognitive disorder. As the conversion to Alzheimer's disease (AD) progresses, patients’ symptoms (e.g., memory loss, severe impairments in thinking and behavior) place a heavy toll on their caregivers, family, and friends, who face emotional frustration, coupled with great financial stress. Furthermore, in terms of global cost estimation, the World Health Organization predicted that by 2030, the treatment of patients with AD and other forms of acquired cognitive impairment will cost the healthcare system US$1.7 trillion (or US$2.8 trillion, if corrected for the increase in care costs).