TOPLINE:

Premorbid depression and delirium were linked to more than threefold and sixfold increased risks, respectively, for progressive supranuclear palsy (PSP), with the risk remaining significant 5-10 years before PSP diagnosis, a new study showed. Heavy alcohol consumption and functional gastrointestinal (GI) disorders were also linked to an increased risk for PSP, whereas cancer was linked to a decreased risk.

METHODOLOGY:

• A nested case-control study used data from the prospective UK Biobank cohort for 240 adults (mean age, 64 years; 58% men; 98% White individuals) with incident PSP, a rare brain disease that affects balance, eye movements, and cognition. Cases were identified from 2007 to 2025 using data from death registries, self-reports, or secondary/tertiary care.
• The patients were matched by age and sex to 2400 control individuals without Parkinson’s disease or dementia.
• Premorbid sociodemographic, lifestyle, environmental, and medical factors were examined and risk factors for PSP were derived.
• Significant medical comorbidities were examined at different timepoints (1, 3, 5, and 10 years) before PSP diagnosis using models adjusted for age and sex.

TAKEAWAY:

• In the fully adjusted model, premorbid depression was associated with an increased risk for PSP (odds ratio [OR], 3.2; P < .001), and this association remained significant 10 years before the diagnosis (OR, 2.1; P < .001).
• A delirium diagnosis was also linked to PSP risk (OR, 6.8; P < .001), which remained significant 5 years before PSP diagnosis (OR, 10.1; P = .02).
• Functional GI disorders were associated with an increased PSP risk (OR, 1.9; P < .001), and heavy alcohol consumption was associated with a higher risk than moderate consumption (OR, 1.65; P = .002).
• Cancer diagnosis was inversely associated with the risk for PSP (OR, 0.56; P < .001), and this relationship remained significant 1 year before PSP diagnosis (OR, 0.7; P = .04).

IN PRACTICE:

“These findings raise important questions related to the pathophysiology and premorbid clinical manifestations of PSP and other syndromes related to frontotemporal lobar degeneration,” the investigators wrote.

“Future large prospective cohort studies integrating longitudinal imaging, genomics, and mechanistic biomarkers will be essential to clarify causality and evaluate whether these premorbid risk factors can improve early detection of PSP,” they added.

SOURCE:

This study was led by Charlie Weige Zhao, MD, Massachusetts General Brigham, Boston. It was published online on March 24 in Movement Disorders.

LIMITATIONS:

This study was limited by an undefined positive predictive value for PSP because of its low prevalence, as well as by a lack of pathologic confirmation of diagnoses, a predominantly White and healthy patient population, a small number of PSP cases, exclusion of genetic factors, and a low prevalence of early comorbidities and overall comorbidity.

DISCLOSURES:

This study was funded by the Dolce family fund for PSP at Massachusetts General Hospital, Boston. Disclosure information for study authors is available in the original study publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.