Clinicopathological Heterogeneity of Lewy Body Diseases: The Profound Influence of Comorbid Alzheimer’s Disease

Thomas G. Beach MD, PhD, FRCPC

Director of Neuroscience, Banner Sun Health Research Institute
Director, Arizona Study of Aging and Neurodegenerative Disorders (AZSAND)
Director, Brain and Body Donation Program

 

Faculty Host: Sheng Zhong, Ph.D.

 

 


Seminar Information

Seminar Date
November 8, 2024 - 2:00 PM

Location
The FUNG Auditorium - PFBH

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Abstract

In recent years, proposals have been advanced to redefine or reclassify Lewy body disorders by merging the long established entities of Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB). These proposals reject the International DLB Consortium classification system that has evolved over three decades of consensus collaborations between neurologists, neuropsychologists and neuropathologists. While the Consortium one year rule for separating PD and DLB has been criticized as arbitrary, it has been a pragmatic and effective tool for splitting the continuum between the two entities. In addition to the decades of literature supporting the non-homogeneity of PD and DLB, it has become increasingly apparent that Lewy body disorders may fundamentally differ in their etiology.  Most PD subjects, as well as most clinically presenting DLB subjects, might best be classified as having a primary synucleinopathy while most clinically-unidentified DLB subjects, who also have concurrent neuropathology-criteria AD (AD DLB), as well as those with neuropathological AD and amygdala-predominant LBD insufficient for a DLB diagnosis, may best be classified as having a secondary synucleinopathy.  Importantly, the DLB Consortium recognized the importance of comorbid AD pathology by defining Low, Intermediate and High subdivisions of DLB based on the relative brain stages of both Lewy body and AD pathology. If the one year rule for separating PD from DLB, and for then dividing DLB into subtypes based on the presence and severity of comorbid AD pathology, is effective, then the divided groups should statistically differ in important ways. In this study we used the comprehensive clinicopathological database of the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) to empirically test this hypothesis. Furthermore, we used multivariable statistical models to test the hypothesis that comorbid AD neuropathology is a major predictor of the presence and severity of postmortem Lewy synucleinopathy.  The results confirm the clinicopathological heterogeneity of Lewy body disorders as well as the profound influence of comorbid AD pathology.

Speaker Bio

Thomas Beach is Director of Neuroscience at Banner Sun Health Research Institute (BSHRI) in Sun City, Arizona. He was trained in neuroscience and neuropathology at the University of British Columbia (UBC) and did clinical training at UBC, New York Medical College and St. Louis University. He was appointed Assistant Professor at UBC in 1993, moving to Phoenix, Arizona in 1997, when he assumed directorship of the Civin Laboratory for Neuropathology and AZSAND. Dr. Beach has been the recipient of multiple grants and awards from agencies including the National Institutes of Health, Alzheimer’s Association, the state of Arizona and the Michael J. Fox Foundation for Parkinson’s Research. He has been Neuropathology Core Leader of the Arizona Alzheimer’s Disease Center since its inception in 2001. He has been an author on more than 500 publications listed by the US National Library of Medicine. Additionally, he has served industry as a consultant and as a neuropathology core leader for several imaging-to-autopsy FDA-licensing clinical trials. His research is focused on elucidating early neuropathological stages and biomarkers of normal human aging, Parkinson’s disease,
Alzheimer’s disease and other neurodegenerative diseases. His studies center on the structural and neurochemical changes of the human central and peripheral nervous system, through autopsy, biopsy and neuroimaging.