Early clinical characteristics of pathologically confirmed progressive supranuclear palsy and corticobasal degeneration.

OBJECTIVES

Although the clinical features of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are well documented, their early clinical presentations from the perspective of initial clinical consultation remain less well understood. This study aimed to characterize the early clinical features of PSP and CBD to inform clinicians on diagnostic assessment and management strategies.

METHODS

Data were obtained from the National Alzheimer's Coordinating Center (NACC) database (2005-March 2025 data freeze). Neuropathologically confirmed cases of PSP (n = 278) and CBD (n = 149) were included. Analyses were restricted to first clinical visits, focusing on demographic, neuropsychiatric, neurological, and neuropsychological variables.

RESULTS

Memory symptoms were reported in more than half of both groups, whereas language impairment was more common in CBD (> 70%) and associated with higher odds of CBD diagnosis. Depression was frequent (~ 50%), with PSP showing higher odds for depressive symptoms but lower odds for disinhibition. Although 20-30% of both PSP and CBD patients exhibited no parkinsonian signs at presentation, gait disturbance, falls, and slowness were common and strongly associated with PSP. Approximately half of both groups presented with cognitive-predominant onset, and nearly one-fifth were initially misdiagnosed as Alzheimer's disease.

CONCLUSIONS

A substantial proportion of PSP and CBD patients lack parkinsonian signs at first presentation, and cognitive-onset presentations are frequent, leading to early diagnostic uncertainty. Clinicians should recognize these overlapping features when evaluating early atypical parkinsonian or cognitive syndromes.