Alzheimer’s disease: New diagnostic criteria, new treatments, new considerations
Summary Abstract:
Alzheimer’s disease (AD) was first identified over 100 years ago when Alois Alzheimer used histology techniques to characterize insoluble protein aggregates in postmortem tissue obtained from a patient with presenile dementia. These protein aggregates were later identified as the beta amyloid plaques and neurofibrillary tangles that define the disease pathologically. In the 1980s, formalized diagnostic criteria were codified to unify the field under a single diagnostic framework. The “McKhann criteria” took a neuropsychological approach to characterize a progressive amnestic syndrome coupled with functional decline; a diagnosis of definite AD was only assigned with pathological confirmation of plaques and tangles coupled with evidence of dementia. Guided by the Amyloid Hypothesis, the field advanced quickly to develop CSF and PET biomarkers for amyloid plaques and neurofibrillary tangles, which were incorporated into a new set of diagnostic criteria in 2011 that defined preclinical AD, mild cognitive impairment (MCI), and dementia due to AD. These criteria centered on the severity of symptoms but incorporated biomarkers to complement the neuropsychological diagnostic features. In 2018, a National Institute on Aging (NIA) and Alzheimer’s Association (AA) committee formulated a research framework with diagnostic criteria that radically departed from previous iterations. The NIA-AA criteria relied exclusively on biomarker evidence of amyloid and tau pathology to diagnose AD, without a requirement for cognitive impairment. The development of biomarkers continued to advance and new techniques to detect ultra-low protein concentrations in biofluids ushered in a new generation of blood-based biomarkers. In 2023, a new NIA-AA committee proposed AD diagnostic criteria intended to be used in both clinical and research contexts. These criteria operationalize AD as the presence of amyloidosis alone but offer a detailed framework to stage the pathophysiological and clinical severity of AD. The evolution of the diagnostic criteria, biomarkers, and treatment strategies for AD, which focus primarily on removal of amyloid pathology with monoclonal antibodies, has advanced rapidly and define an AD research and clinical landscape centered around biomarkers.
The current symposium provides a forum to discuss the recent developments in the conceptualization, diagnosis, and treatment of AD. Dr. Ozioma Okonkwo, a member of the NIA-AA 2023 working group, will discuss the evolution and current structure of the diagnostic criteria. Dr. Thomas Karikari, an international authority on blood-based biomarkers, will discuss the current state of AD and related biomarkers. Dr. Adam Brickman will contextualize a modern biomarker conceptualization of AD and the role of neuropsychologists in today’s research and clinical milieu. Finally, Dr. Jennifer Manly will elucidate the consequences of lack of inclusion of marginalized groups during all stages of development and validation of AD criteria, offer essential components of a framework for a more equitable AD science, and highlight the significance of neuropsychology for advancing equity in AD research. The symposium will encourage dialog among attendees in an open discussion session at its conclusion.
Number of Credit Hours: 1.5
Level of Instruction: Intermediate
Learning Objectives:
1. To learn about new NIA-AA diagnostic criteria for Alzheimer's disease
2. To learn the state of blood-based biomarkers for Alzheimer's disease and related disorders
3. appreciate some caveats in Alzheimer’s disease conceptualization and the significance of neuropsychology for advancing equity in AD research
Presenter(s):
Adam M. Brickman, PhD
Columbia University
Dr. Brickman is a Professor of Neuropsychology at Columbia University.
Ozioma Okonkwo, PhD
UW-Madison
Dr. Okonkwo is a Professor in the Department of Medicine. He received his PhD from the University of Alabama at Birmingham and completed his postdoctoral training at Johns Hopkins University School of Medicine. Dr. Okonkwo’s research focuses on clarifying how alterations in the brain and other biomolecules place some cognitively-normal individuals on a pernicious trajectory that culminates in probable Alzheimer’s disease. In this context, Dr. Okonkwo is also interested in discovering new knowledge concerning the modulation of the link between brain changes and cognitive decline by both modifiable and non-modifiable factors. Overlaid on this research agenda are investigations of health inequities, and how such inequities exacerbate or ameliorate the impact of biomarkers on clinical phenotypes.
Thomas Karikari, PhD
University of Pittsburgh
Dr. Karikari is an Assistant Professor of Psychiatry and Director of the Biofluid Biomarker Laboratory at the University of Pittsburgh, and serves as the Director of the Mass Spectrometry Program and the Single Molecule Analytics Program at the Department of Psychiatry, University of Pittsburgh. He is also Co-Director of the Neurogenetics & Biomarker Core of the University of Pittsburgh Alzheimer’s Disease Research Center.
Dr. Karikari is a globally recognized expert in the discovery, method development, technical validation, and real-world implementation of biofluid biomarkers for Alzheimer’s disease and related neurodegenerative diseases. His research program covers basic and translational science as well as clinical applications. His laboratory focuses on studying the biochemical, molecular and functional bases of neurodegenerative pathologies in the human brain and biofluids.
Jennifer Manly, PhD
Columbia University
Jennifer J. Manly, Ph.D. is a Professor of Neuropsychology in the Department of Neurology at Columbia University Irving Medical Center. Her research focuses on mechanisms of inequalities in cognitive aging and Alzheimer’s Disease. Her research team has partnered with the Black and Latinx communities in New York City and around the United States to design and carry out investigations of structural and social forces across the lifecourse, such as educational opportunities, discrimination, and socioeconomic inequality, and how these factors relate to cognition and brain health later in life. She is the MPI of the Columbia Interdisciplinary Research Center on Alzheimer’s Disparities which focuses on mentoring early career scientists from minoritized backgrounds. Her research has been funded by the National Institutes of Health and the Alzheimer’s Association, and she has authored over 220 peer-reviewed publications and 10 chapters. She was the 2014 recipient of the Tony Wong Diversity Award for Outstanding Mentorship, was the recipient of the Paul Satz-International Neuropsychological Society Career Mentoring Award in 2020, and was named the Irving Institute for Clinical and Translational Research Senior Mentor of the Year in 2022. Dr. Manly was elected to the National Academy of Medicine in 2021. She served on the HHS Advisory Council on Alzheimer's Research, Care and Services from 2011 – 2015 and is a current member of the National Advisory Council on Aging.
