Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Progressive supranuclear palsy (PSP) is a tauopathy for which there is limited understanding of epidemiological risk factors. OBJECTIVE: The objective of this study was to identify premorbid nonmedical and medical risk factors for PSP diagnosis in a large prospective population-based cohort. METHODS: We performed a matched nested case-control study using the UK Biobank (UKB) cohort consisting of >500,000 adults aged 37 to 73 years. PSP diagnoses were identified from 2007 to censor date (August 2025) and matched 1:10 by age and sex to control subjects without parkinsonism or dementia diagnoses. We derived risk factors using an iterative logistic regression approach. RESULTS: There were 240 incident PSP diagnoses in the UKB. In the fully adjusted model, premorbid depression (odds ratio [OR], 3.22; 95% confidence interval [CI], 2.30-4.50; P < 0.001), delirium (OR, 6.76; 95% CI, 4.08-11.19; P < 0.001), and functional gastrointestinal disorders (OR, 1.91; 95% CI, 1.39-2.63; P < 0.001) were associated with increased risk. Heavy alcohol consumption was associated with higher risk compared with moderate consumption (OR, 1.65; 95% CI: 1.21-2.26; P = 0.0017). Body mass index (BMI) and alcohol consumption had nonlinear risk profiles. Cancer diagnosis was inversely associated with PSP (OR, 0.56; 95% CI, 0.40-0.79; P < 0.001). Depression and delirium diagnoses remained significant 5 to 10 years before diagnosis. CONCLUSIONS: In this large prospective cohort, PSP was associated with premorbid lifestyle practices and neuropsychiatric diagnoses years before diagnosis. This suggests a long premotor phase and highlights opportunities for earlier diagnosis and further mechanistic investigation. The inverse association with cancer mirrors the relationship seen in other neurodegenerative conditions and may point toward shared mechanisms. © 2026 International Parkinson and Movement Disorder Society.
Source: Movement Disorders
DOI: 10.1002/mds.70287
Institutions: Harvard University, Mass General Brigham, Oregon Health & Science University, Johns Hopkins University, University Health Network, University of Toronto, University of Rochester Medicine, University of Rochester, University of California San Diego, Medical University of South Carolina, Mayo Clinic in Florida, University of Chicago, University of Chicago Medical Center, Rutgers, The State University of New Jersey, CurePSP, MRC Cognition and Brain Sciences Unit, University of Cambridge
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7140217319