Clinical correlates of cognitive impairment in progressive supranuclear palsy and multiple system atrophy: a comparative neuropsychological study

Abstract Background Atypical Parkinsonian Syndromes (AP), such as Progressive Supranuclear Palsy (PSP), Multiple System atrophy (MSA), are characterized by motor and non-motor symptoms. Although cognitive impairment is a core feature of AP, its differential profile across AP syndromes has been inadequately understood, particularly in underrepresented populations like in India. Aim To compare cognitive and neuropsychological profiles in PSP and MSA and examine their clinical correlates. Methods In this cross-sectional study, AP patients underwent cognitive assessment using the Frontal Assessment Battery (FAB), the Montreal Cognitive Assessment (MoCA), the Addenbrooke’s Cognitive Examination-III (ACE-III), and selected neuropsychological tests from the NIMHANS Neuropsychology Battery for the elderly (NNBE). Between-group comparisons were conducted using age-adjusted ANCOVA. Partial correlations examined associations between cognition and clinical variables within each group. Results A total of 159 patients were included in which PSP (n = 98, mean age 62.5 ± 7.4 years) was older than MSA (n = 61, 58.6 ± 7.8 years). Groups were gender-matched (p = 0.48). After age adjustment and FDR correction, PSP showed significantly lower scores than MSA on FAB, MoCA, and ACE-III Total, as well as on fluency, attention, visuospatial construction, and visuospatial working memory measures (all corrected p < 0.05). In PSP, cognitive performance correlated with education, motor severity (UPDRS-III, PSPRS), and mood (all p < 0.05), whereas in MSA, cognition correlated only with education and multilingualism, with no significant association with motor or symptom severity. Conclusion PSP demonstrates greater global and domain-specific cognitive impairment than MSA, particularly in fluency and working memory, with cognition more closely tied to motor and mood burden. In MSA, cognition is more reserve-driven. Routine cognitive screening may aid early differentiation and clinical management of AP.