Cognitive and behavioral disturbances in PSP and MSA: clinical features and imaging correlates

Cognitive and behavioral disturbances are increasingly recognized as core features of Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), with important clinical and prognostic implications. In PSP, cognitive impairment-often an early sign-is dominated by a dysexecutive syndrome linked to dorsolateral prefrontal atrophy and fronto-subcortical circuit disruption. Deficits also extend to attention, memory, language, visuospatial abilities, and social cognition. Apathy is the most common behavioral symptom, associated with medial prefrontal and subcortical atrophy, while impulsivity, disinhibition, and mood symptoms reflect broader orbitofrontal and posterior cortical involvement. Imaging studies highlight frontooccipital white matter disruption and subcortical tau deposition as key contributors to these features. In MSA, cognitive impairment is typically milder and more variable, most commonly involving executive dysfunction related to fronto-subcortical and cerebellar degeneration. Memory and visuospatial issues usually stem from impaired executive control. Behavioral symptoms-especially apathy and depression-are frequent but underrecognized. Frontal and cerebellar atrophy, along with disrupted striato-frontal connectivity and reduced metabolism, correlate with these changes. Autonomic dysfunction, particularly orthostatic hypotension, may further exacerbate cognitive decline through cerebral hypoperfusion. These findings underscore the importance of early detection of cognitive and behavioral symptoms in PSP and MSA. Given their significant impact on quality of life and functional decline, comprehensive assessment tools and multidisciplinary care approaches are essential to improve outcomes.