Division of Neuroscience
The National Institute on Aging’s (NIA) commitment to the systematic study of the aging brain began with its establishment in 1974, and its support of neuroscience research, including research on Alzheimer’s disease (AD), has increased dramatically since then. The NIA legislative mandate provides specific authority to support research on AD, establish AD research centers, conduct clinical trials for the treatment of AD, and promote research on the etiology, treatment, and diagnosis of AD.
Among the many age-related impairments that lead to institutional care, those related to changes in brain functioning have the most significant implications for public policy and priorities for further research. Changes in the brain, especially those that affect sensory, motor, sleep, cognitive, and emotional functioning, profoundly influence the quality of life of older individuals. Reduced functional capacity not only limits independence but also influences the attitudes of others toward the aging person, affects the individual’s self-image, and often determines the nature and quality of health-care services.
Through its investment in neuroscience research, NIA is committed to solving not only the problems of dementias of old age, but also to further understanding of the normally aging brain.
Within the NIA, the Division of Neuroscience (DN) fosters and supports extramural and collaborative research and training to further the understanding of neural and behavioral processes associated with the aging brain. An area of special emphasis is brain-behavior relationships. An important component of this Division is the support of basic, clinical, and epidemiological studies of AD and related dementias of aging.
The Division of Neuroscience is composed of three branches: Neurobiology of Aging, Behavioral and Systems Neuroscience, and Dementias of Aging. Overall, the Division supports a broad spectrum of research aimed at elucidating how the central nervous system and behavior are affected by normal as well as pathological aging. An emerging focus is how the processes of aging and age-related cognitive decline intersect with the development of Alzheimer’s disease (AD) and other dementias of aging. The basic theme throughout the Division is to understand the aging nervous system in order to foster the maintenance of health and improve the quality of life of the older population.
Extramural Program Office Manager
The mission of the Neurobiology of Aging Branch is to support research aimed at elucidating how the nervous system is affected by normal as well as pathological aging. The branch is divided into three sections: Fundamental Neuroscience, Integrative Neurobiology, and Sleep and Biological Rhythms. This Branch encompasses areas of neuroscience exclusive of research focused on the dementias of aging, and fosters research from the most basic levels to the translation of research findings into interventions promoting the health of the public.
Several motifs highlight the research questions funded by the Neurobiology of Aging Branch. These are: selective vulnerability of regions of the central nervous system (CNS) to aging effects; molecular genetics of brain aging; oxidative stress, bioenergetic processes and cell death mechanisms; cellular and molecular mechanisms of neural plasticity and brain repair processes; interactions between organ systems (especially the immune, endocrine, and central nervous systems) through common signaling molecules and the potential to uncouple the normal interactions of these systems by age-associated changes, and circadian pacemakers and age-related mechanisms underlying sleep-wakefulness cycles.
The ultimate goal of such research is the maintenance of a high quality of life of the older population through a better understanding of the aging nervous system and the application of basic research findings to improve and correct age-associated neuropathologies.
Fundamental Neuroscience encompasses a range of research areas and methodologies under the unifying theme of research at the cellular, molecular, and genetic levels that will elucidate age-related structural and functional changes. Of particular interest is selective vulnerability of neural cells to loss of function or neurodegeneration that may occur in aging. Research areas include molecular genetics of brain aging; gene and protein homeostasis; mechanisms of neuronal cell death; cell energy metabolism and oxidative stress; involvement of glial cells in brain aging; neural stem cells and cell repair/replacement in the brain; and molecular mechanisms involved in neuronal plasticity in response to environmental influences and age. The interaction between systemic metabolism and the CNS is also an area of interest. In particular, research that examines the mechanistic links between disrupted systemic metabolism, cerebrovascular integrity and brain aging is supported. This section supports translational research focused on basic strategies for neuroprotection and neurorepair, which lays the foundation for clinical intervention studies.
Integrative Neurobiology is focused on neural mechanisms underlying age-related changes in endocrine functions; neurodegenerative diseases of aging associated with conventional and unconventional (prions) infectious agents, central nervous system, neuroendocrine system, and immune system interactions in aging; and the development of clinical trials and novel interventions to treat these pathologies .A major focus of the research supported by this Section is on the neural control of the senescence of reproductive function as well as the reciprocal control of the relevant hypothalamic regions and gonadal hormones. Of growing importance is the recognition that in humans as well as in other organisms, there are networks of organ systems, for example, the endocrine, immune, and nervous systems that share signal molecules, transmit information within and between systems, and mutually regulate their complex interactions. Disruption of these interactions, such as through stress, may result in impaired homeostatic controls, which lead to increased host susceptibilities to disease.
Sleep and Biological Rhythms encompasses the areas of epidemiology, etiology, pathogenesis, diagnosis, treatment, and prevention of sleep disorders of older people; age-related mechanisms underlying sleep-wake cycles and behavioral sequelae in the aged, and effects of normal and disordered biorhythmicity of the aging nervous system .Because abnormal sleep in the older person reflects concurrent disease states, as well as alterations of circadian rhythmicity, and sleep processes, further elucidation of the underlying mechanisms and of their translation into clinical trials and effective interventions are necessary. Of special interest are the consequences of sleep deprivation upon such functions as cognition, metabolic processes, and health and well-being.
Bradley C. Wise, Ph.D.
Robin Walter, M.S.
Research Program Analyst
Fundamental Neuroscience Section
Suzana S. Petanceska, Ph.D.
Program Director, Fundamental Neuroscience; Systemic Metabolism, Vasculature, Receptors
Bradley C. Wise, Ph.D.
Program Director, Fundamental Neuroscience; Neurodegeneration, Neuroplasticity, Bioenergetics, and Glia
Integrative Neurobiology Section
Miroslaw Mackiewicz, Ph.D.
Program Director, Integrative Neurobiology
Sleep and Biological Rhythms Section
Miroslaw Mackiewicz, Ph.D.
Program Director, Sleep and Biological Rhythms
The mission of the Behavioral and Systems Neuroscience Branch is to support research aimed at elucidating the age-related alterations in neural systems that support behavioral functions such as cognition, emotion, movement, perception and sensory function. The branch is divided into two sections: Cognitive and Affective Neuroscience and Sensory/Motor Disorders of Aging. Clarification of cognitive, emotional, sensory and motor changes with age and the psychological and/or biological mechanisms underlying them are necessary pre-requisites for disassociating the effects of normal aging from those due to disease. Model systems, including computational models, invertebrates, and mammals, are central to this effort.
The ultimate goal of such research is to foster the understanding of individual differences in cognitive, emotional, sensory, and motor function with age; and to elucidate the molecular, cellular and systems level mechanisms underlying age-related change in these behaviors. Better understanding of these mechanisms is important for planning therapeutic interventions, for appropriately using and enhancing skills and expertise of older people, and for specifying the requirements of an aging society.
Cognitive and Affective Neuroscience supports a wide range of research on and research approaches to attention, learning, memory, executive function, language, emotion, reasoning, decision-making, and judgment and how these capacities may change with age and experience. The use of molecular and cellular approaches, systems approaches, computational and integrative approaches is encouraged; studies linking neuroscience and cognitive science approaches to aging are emphasized. A focus is the application of state-of-the-art neuroimaging technologies to study structural and dynamic brain changes and adaptations in aging. The presence of co-morbidities with age, their role in impacting cognitive or emotional function, and the existence of possible common pathways and treatments are important to understand. Also of paramount interest is research to elucidate the roles of genes, life experience, environment and culture in promoting plasticity and adaptability of the aging brain and behavior. An emphasis is on understanding and treating age-related cognitive decline and investigating its relationship to cognitive decline characteristic of AD and other dementias.
Sensory/Motor Disorders of Aging supports research on mechanisms of normal aging and disease-related alterations in motor, visual, auditory, somatosensory, proprioceptive, vestibular, and chemosensory functions, as well as pain. Approaches utilized include: genetic, cellular, molecular, imaging, behavioral, pharmacological, computational, clinical, and epidemiological investigations. Of particular interest is research on age-related changes in central nervous system pathways, and functional implications of interactions among multiple sensory systems or sensory and motor systems. Some examples include: delineating and comparing the effects of normal aging versus neurodegenerative processes or diseases on sensory or motor function; designing assistive technologies to enhance older adults’ sensory and/or motor functions; and developing intervention or prevention strategies for age-related sensory or motor impairments. The motor system research projects supported by this program include: understanding mechanisms of postural control and balance; sensory-motor integration; and movement disorders in aging, including parkinsonism, Parkinson's disease and amyotrophic lateral sclerosis.
Molly V. Wagster, Ph.D.
Research Program Analyst
Cognitive and Affective Neuroscience Section
Molly V. Wagster, Ph.D.
Program Director, Mechanisms of Cognitive and Emotional Aging, Cognitive Neuroscience, Co-morbidities
Sensory and Motor Disorders of Aging Section
Wen G. Chen, Ph.D.
Program Director, Sensory and Motor Disorders of Aging
The mission of the Dementias of Aging Branch is to support research on the etiology, epidemiology, diagnosis, treatment, and prevention of Mild Cognitive Impairment (MCI), AD, and other dementias (e.g. Vascular Dementia, Frontotemporal Dementia, Lewy Body Dementia) of older people. This research encompasses basic, clinical, and epidemiological studies as well as clinical trials of these disorders and diseases. The Branch is composed of four sections:Basic Research, Population Studies, Clinical Studies, and Research Centers. There is a close collaboration among the Neurobiology, Behavioral and Systems Neuroscience, and Dementias Branches because of the shared interests involving age-related cognitive decline, MCI, and AD.
The ultimate goal of the research supported by the Dementias of Aging Branch is the pre-symptomatic identification of the earliest brain changes that ultimately result in dementia in conjunction with the development of therapeutics which will be able to delay disease onset or progression or to prevent disease entirely.
Basic Research supports research on the etiology of MCI, AD and other age-related neurodegenerative disorders, including studies to identify genetic loci associated with inherited and sporadic forms of these diseases; biochemical and molecular genetic analysis of the components of amyloid plaques, neurofibrillary tangles, and other abnormal structures found in the brains of individuals with MCI, AD, and other dementias of aging and the molecular consequences of their accumulation .Studies are supported on all mechanisms of neuronal dystrophy and death, including the roles of signal transduction, protein trafficking, protein phosphorylation, proteolysis, neuroimmune function, neuroendocrine function, oxidative mechanisms, cerebral metabolism, toxins and infections. This Section also supports research on the interactions between systemic metabolism and the CNS during pathological aging of the brain to understand the mechanistic link between individual metabolic abnormalities that constitute the metabolic syndrome and AD pathogenesis. This Section emphasizes translational research building on basic findings to develop strategies for interventions.
Population Studies supports research in the epidemiology of age-related cognitive dysfunction, MCI, AD, and other dementias. Areas of special interest include domestic, cross-cultural, and international epidemiological studies of the age-specific incidence and prevalence rates and risk and protective factors for MCI, AD, and other dementias; the development and testing of epidemiological models for dementing diseases; the natural history, clinical course, co-morbid conditions, and causes of death in patients with age-related cognitive dysfunction, MCI, AD, and other dementing diseases; familial aggregation studies; and the development of sensitive and specific cognitive and diagnostic screening instruments for use in heterogeneous and culturally varied populations.
Clinical Studies supports research on the diagnosis, clinical course, treatment, and management of individuals with age-related cognitive dysfunction, MCI, AD, and other dementias of aging. Research on diagnosis is aimed at the development and evaluation of reliable and valid multidimensional diagnostic procedures and instruments .Research is solicited on the identification and testing of preclinical and antemortem biological, chemical, neuroimaging, and behavioral markers for age-related cognitive dysfunction, MCI, and AD; refinement of methods for diagnostic assessment and tracking clinical course, including studies of neuropsychological batteries and neuroradiological techniques, clinical, and neuropathological concordance studies, and natural history, clinical course, comorbid conditions, and causes of death for age-related cognitive dysfunction, MCI, AD, and other dementias of aging.
Research in the treatment and management of the earliest pathological changes of age-related cognitive dysfunction, MCI, AD, and other dementias seeks to develop the understanding required to slow their course, treat and manage the cognitive and behavioral manifestations, and, ultimately, to delay the onset of and to prevent them .Approaches include clinical trials of pharmacologic agents, behavioral, and environmental interventions, as well as preclinical drug discovery and development studies leading to novel compounds for prevention and treatment of these disorders. Studies aimed at the preservation of function and reduction of excess disability, insomnia, agitation, etc. are also of interest.
The Research Centers supports the Alzheimer's Disease Center (ADC)Program including the Alzheimer's Disease Research Centers (ADRC) and the Alzheimer's Disease Core Centers(ADCC),as well as the National Alzheimer's Coordinating Center (NACC), and the National Cell Repository for AD (NCRAD).The ADC program supports a multifaceted approach to AD, including clinical, pathology and other core services, basic and clinical research, professional and public information, and educational activities. Both the ADRCs and the ADCCs provide data and biological samples for expanded multidisciplinary research activities in AD. NACC coordinates sharing of data and samples among the ADCs as well as with non-ADC investigators; indexes resources at each of the ADCs; supports uniform data collection procedures among the ADCs; promotes collaborative research utilizing Center resources and provides administrative data to the NIA. Use of data and samples available through NACC is strongly encouraged. NCRAD collects genetic samples and phenotypic data for genetic studies of early and late onset AD.
Laurie M. Ryan, Ph.D.
Cerise Elliott, Ph.D.
Research Program Analyst
Basic Research Section
Marilyn M. Miller, Ph.D.
Program Director, Etiology of Alzheimer's Disease: Genetics, Tau, Hormone Research
Suzana S. Petanceska, Ph.D.
Program Director, Etiology of Alzheimer's Disease: Systemic Metabolism, Vasculature, Cell Biology, Receptors, Epigenomics
Research Centers Section
Creighton H. Phelps, Ph.D.
Program Director, Alzheimer's Disease Centers and National Alzheimer’s Disease Coordinating Center
Nina Silverberg, Ph.D.
Program Director, Alzheimer's Disease Core Centers
Clinical Studies Section
Lorenzo M. Refolo, Ph.D.
Program Director, AD Drug Discovery and Development
John K. Hsiao, M.D.
Program Director, Diagnosis, Neuroimaging, Biomarkers of AD and AD Neuroimaging Initiative
Laurie Ryan, Ph.D.
Program Director, Alzheimer’s Disease Clinical Trials
Nina Silverberg, Ph.D.
Program Director, Clinical Course, Behavior Management
Population Studies Section
Dallas W. Anderson, Ph.D.
Program Director, Population Studies and Epidemiology of Alzheimer's Disease