White matter hyperintensities (WMH), traditionally linked to cerebral small vessel disease, are frequent in Progressive Supranuclear Palsy (PSP). This study assessed their prognostic value in disease progression.

Sixty PSP patients underwent 3 Tesla Magnetic Resonance Imaging (MRI) at baseline and then were followed for of 48.62 ± 25.11 (mean ± standard deviation) months with extensive neurological evaluations. WMH were rated with the age-related white matter changes (ARWMC) scale (total and lobar), classifying patients into two groups: ARWMC = 0 (without WMH) and ARWMC >0 (with WMH). Outcomes included time to disease milestones (unintelligible speech, wheelchair dependency, PEG placement, death). Kaplan–Meier, Cox regression, and linear mixed models were applied, adjusting for age, sex, and vascular risk factors.

Baseline WMH were present in 65% (mean ARWMC score 4.7 ± 3.3), predominantly in frontal and parietal lobes. The presence of WMH did not significantly influence time to milestones or death. In subregional analyses, higher temporal lobe WMH scores predicted reaching any milestones (HR 3.336, 95% CI 1.698–6.555, p<0.001) and death (HR 2.533, 95% CI 1.297–4.945, p=0.006), even after adjusting for age, sex and ARWMC score of all lobes. No effect of WMH burden on PSP-rs progression was observed.

Overall WMH burden at baseline was not associated with clinical progression in PSP, although temporal lobe WMH may represent a specific prognostic marker. These findings suggest a limited role of WMH in PSP progression and call for advanced imaging studies to clarify their contribution.