A study published in the medical journal Alzheimer’s & Dementia finds disagreement between progressive supranuclear palsy (PSP) diagnoses made in-clinic and brain autopsies in the National Alzheimer’s Coordinating Center’s (NACC)  dataset, which includes people with FTD. A mismatch of diagnosis during life with later autopsy findings is not unique to PSP, and underscores the need for better diagnostic markers. The authors suggest the heterogeneous presentation of PSP and a possible reliance on “classic” movement-based symptoms of the disorder as possible causes for this mismatch.

Studies such as this can lay groundwork for understanding the relationship between symptoms and brain pathology to inform diagnosis and treatment.

First author Tanav Popli, MD, received the 2023 Clinical Research Training Scholarship in FTD, a partnership co-funded by the AFTD Holloway Family Fund and the American Brain Foundation and administered by the American Academy of Neurology.

Under 40% of People with PSP Diagnosed in Clinic

Dr. Popli and his colleagues reviewed data from 230 people in the study; each of the participants fell into one of three categories: people diagnosed with PSP in a clinical setting by a doctor, people who received what is known as a neuropathological diagnosis from a brain autopsy, and those who received both. When the authors analyzed their results, it showed a significant disconnect between clinical and neuropathological diagnosis. 115 people were only diagnosed during a neuropathological workup, 42 were diagnosed in clinic only, and the remaining 73 received a PSP diagnosis during both.

Clinical diagnosis involves a physician conducting a series of specialized exams to check for symptoms and features typical of FTD and other dementias. Because symptoms of PSP overlap with other FTD disorders and dementias like Alzheimer’s and Lewy body dementia (LBD), clinical diagnosis can be difficult. Neuropathological examination reveals the underlying disease and its related proteins (such as tau or TDP-43), which can result in a final diagnosis being different from what was previously given in clinic.

PSP has traditionally been associated with movement-based symptoms, but it is now recognized as having features which overlap with other FTD disorders, like emotional blunting or difficulty problem solving. While there is a PSP subtype known as Richardson Syndrome (PSP-RS) that is primarily associated with classic movement-based symptoms, the authors note that previous research suggests PSP-RS makes up less than half of documented cases. The authors highlight both the symptom overlap and reliance on classic movement-based symptoms of PSP as contributing factors in the mismatched diagnoses.

Co-Occurring Pathologies Associated with Other Disorders Present in Most Participants

When reviewing the neuropathological data from the NACC participants, Dr. Popli and his colleagues discovered that different disease mechanisms were occurring at the same time as PSP in some participants. These co-occurring mechanisms, known as “pathologies”, were detected in 69% of the participants of the study. Pathologies related to another FTD disorder known as corticobasal degeneration (CBD) were detected, alongside Lewy body dementia (LBD) and a specific FTD pathology known as Pick’s disease. Additionally, nearly half of the sample had pathological changes associated with Alzheimer’s disease, and most had some form of vascular-based pathology.

The presence of different disease mechanisms tied to different proteins in the same person is increasingly recognized as a common feature of neurodegenerative disease. The authors speculate that the co-occurrence of disease pathologies could reflect overlapping responses to features of dementia like neuroinflammation. The role of co-occurring diseases in symptoms, however, requires further research.

Researchers Utilized Large, National Dataset in Study

The authors used the NACC’s Uniform Data Set (UDS) to conduct their study, which contains research data collected since 2005 at annual evaluations at Alzheimer’s Disease Research Centers across the US. At the time of the analysis, the NACCUDS contained data from 42,661 unique participants collected across 150,744 visits over 15 years. To be included for analysis in this study, a participant had to have a clinical diagnosis of PSP, a neuropathological diagnosis, or both.

The data from the 230 people selected for the study included the results of screening evaluations conducted at research centers and neuropathological data collected after a participant died.

Learn More About PSP

People with PSP may experience a mixture of movement-related symptoms similar to Parkinson’s disease, as well as behavioral and cognitive symptoms similar to other FTD disorders. You can learn more about how PSP fits under the FTD umbrella and how to find trials working to treat the disease by watching the AFTD webinar Perspectives in FTD Research Webinar: Why PSP and CBS Clinical Trials Matter.

Do you have questions or concerns about PSP? Reach out to AFTD’s HelpLine at 1-866-507-7222 or info@theaftd.org.