This episode is a conversation with Drs. Clifford Jack and Kevin Duff about recent updates to the diagnosis and staging of Alzheimer’s disease (AD). We discuss biological versus clinical/pathological approaches to diagnosing AD, analogies between AD and other medical conditions, the predictive validity of amyloid PET in asymptomatic older adults, the specific purpose of the recent Alzheimer’s Association diagnosis and staging paper, the utility of currently available AD biomarkers, the status of blood-based biomarkers for AD, the amyloid hypothesis, concerns from neuropsychologists about the recent Alzheimer’s Association biological definition of AD, and current state of the science for antiamyloid treatments in AD, among other topics.
About Cliff
The laboratory of Clifford R. Jack Jr., M.D., is engaged in brain imaging research in cognitive aging, Alzheimer’s disease and related disorders.
Dr. Jack’s research team employs MRI and positron emission tomography (PET) to study the biology of brain aging and causes of cognitive impairment and develops image-processing algorithms for quantitatively measuring the information obtained from brain imaging. They employ a variety of MRI-based brain imaging modalities, including structural MRI, spectroscopy, functional connectivity and brain water diffusion. They also employ F-fluorodeoxyglucose positron emission tomography (FDG-PET) and amyloid PET.
The lab’s clinical imaging research is tightly integrated into the Mayo Clinic Alzheimer’s Disease Patient Registry (Mayo Clinic Study of Aging) and Mayo’s Alzheimer’s Disease Research Center, which conduct National Institutes of Health-funded longitudinal clinical and epidemiological research projects investigating normal aging, Alzheimer’s disease and other dementias.
Dr. Jack also collaborates with a number of investigators outside Mayo, and his laboratory is the imaging center for several large national multisite studies.
About Kevin
Dr. Kevin Duff has specialized in neuropsychology for over 20 years. He obtained his Ph.D. in Clinical Psychology from the State University of New York in Albany. He completed his neuropsychology internship at the Southern Arizona Healthcare System in Tucson, AZ, and his post-doctoral fellowship at the University of Oklahoma Health Sciences Center in Oklahoma City. He joined the Psychiatry Department at the University of Iowa in 2003, where had clinical and research responsibilities working with patients with dementia, Huntington’s disease, and a variety of other neuropsychiatric conditions. In 2009, he joined the University of Utah as Associate Professor of Neurology and neuropsychologist for Alzheimer’s Care, Imaging and Research. In 2022, he moved (hopefully for the last time) to Oregon Health & Science University in Portland, where he is the senior neuropsychologist at the Layton Aging & Alzheimer’s Disease Research Center and Professor in their Department of Neurology.
Dr. Duff’s research has focused primarily on the early identification of cognitive decline in neuropsychiatric illnesses. Across multiple studies, Dr. Duff has used short-term practice effects as a marker of brain plasticity in patients with Mild Cognitive Impairment to examine if short-term changes in cognition can predict the diagnosis and prognosis of dementia, as well as its brain pathology and response to interventions. He has published over 180 peer-reviewed papers in scientific journals and he has lectured nationally and internationally on his areas of expertise. His research on practice effects in Mild Cognitive Impairment has been continually funded by the National Institutes of Health since 2005.
References
Dubois, B., Villain, N., Frisoni, G. B., Rabinovici, G. D., Sabbagh, M., Cappa, S., … & Feldman, H. H. (2021). Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group. The Lancet Neurology, 20(6), 484-496.
Dubois, B., Villain, N., Schneider, L., Fox, N., Campbell, N., Galasko, D., … & Frisoni, G. B. (2024). Alzheimer disease as a clinical-biological construct—an International Working Group recommendation. JAMA neurology.
Hampel, H., Hu, Y., Cummings, J., Mattke, S., Iwatsubo, T., Nakamura, A., … & Schindler, S. E. (2023). Blood-based biomarkers for Alzheimer’s disease: Current state and future use in a transformed global healthcare landscape. Neuron, 111(18), 2781-2799.
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Jack Jr, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., … & Trojanowski, J. Q. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. The Lancet Neurology, 9(1), 119-128.
Jack Jr, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., … & Trojanowski, J. Q. (2013). Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. The lancet neurology, 12(2), 207-216.
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Jack Jr, C. R., Andrews, J. S., Beach, T. G., Buracchio, T., Dunn, B., Graf, A., … & Carrillo, M. C. (2024). Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimer’s & Dementia.
Kiselica, A. M., Atkinas, K. J., Han, S. D., Diaz-Orueta, U., Gogniat, M. A., Blanco-Campal, A., … & Duff, K. (2024). Reactions of clinical neuropsychologists to the Alzheimer’s Association workgroup’s draft diagnostic and staging criteria for Alzheimer’s disease. Journal of Alzheimer’s Disease, 13872877241292089.
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van der Schaar, J., Visser, L. N., Ket, J. C., Groot, C., Pijnenburg, Y. A., Scheltens, P., … & van der Flier, W. M. (2023). Impact of sharing Alzheimer’s disease biomarkers with individuals without dementia: a systematic review and meta‐analysis of empirical data. Alzheimer’s & Dementia, 19(12), 5773-5794.
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