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However, they can be diagnostically challenging, rapidly progressive and are often diagnosed late in disease course. Their different demographic features and prognoses are well studied, but the accompanying cognitive and psychiatric features may also facilitate diagnosis. Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) may cause cognitive and behavioural manifestations that overlap with frontotemporal dementia, including non-fluent aphasia, apathy and impulsivity. Clinical diagnostic criteria have limited sensitivity, with pathologically confirmed PSP often having presented an initial clinical syndrome other than PSP-Richardson's syndrome.<\/jats:p>\n               <jats:p>Here, we integrate cross-sectional multicentre baseline data from the PROSPECT-M-UK and Oxford Discovery cohorts. This allowed us to compare cognitive and psychiatric features across a total of 1138 people with PSP, CBS, multiple-system atrophy (MSA) and idiopathic PD. Data from the different cohorts were harmonized and compared using multiple linear regression.<\/jats:p>\n               <jats:p>There were five key results: (i) different syndromes showed distinctive cognitive profiles, using readily applicable \u2018bedside\u2019 screening tools. Frontal executive dysfunction was most evident in PSP, visuospatial deficits in CBS, with milder deficits in memory and executive function in MSA, as compared with PD; (ii) the most prevalent neuropsychiatric features were depression and anxiety in CBS, apathy in PSP, with sleep disturbances common in PD. As expected, apathy correlated positively with impulsivity across all disorders. Neuropsychiatric features were generally better at discriminating between atypical parkinsonian syndromes than were the cognitive domains; (iii) both cognitive function and motor severity declined with disease duration, and motor function predicted cognition in PSP, CBS and PD but not in MSA, suggesting that in MSA cognitive and motor dysfunction are decoupled; (iv) plasma neurofilament light chain (NFL) levels, measured in a subset of patients, correlated with cognitive deficits in PSP, but not motor deficits; (v) cognitive deficits contributed to the impairment in activities of daily living after controlling for motor severity, with every two points on the Montreal Cognitive Assessment worsening the Schwab and England score by one point.<\/jats:p>\n               <jats:p>In anticipation of future neuroprotective therapies, we present a classifier to improve diagnostic accuracy for atypical parkinsonian syndromes in vivo. Longitudinal cohort studies with resources for neuropathological gold standard diagnosis remain important to validate better diagnostic tools for people with PSP, CBD, MSA and atypical parkinsonism.<\/jats:p>","DOI":"10.1093\/brain\/awaf132","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T14:15:15Z","timestamp":1744812915000},"page":"3239-3251","source":"Crossref","is-referenced-by-count":11,"title":["Cognitive and neuropsychiatric profiles distinguish atypical parkinsonian syndromes"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-5841","authenticated-orcid":false,"given":"Michele T","family":"Hu","sequence":"first","affiliation":[{"name":"Division of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford and Oxford University Hospitals NHS Trust , Oxford OX3 9DU ,","place":["UK"]},{"name":"Nuffield Department of Clinical Neurosciences, Oxford Parkinson\u2019s Disease Centre, University of Oxford and Oxford University Hospitals NHS Trust , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin Querejeta","family":"Coma","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, Oxford Parkinson\u2019s Disease Centre, University of Oxford and Oxford University Hospitals NHS Trust , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7216-8679","authenticated-orcid":false,"given":"James B","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 OQQ ,","place":["UK"]},{"name":"Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge , Cambridge CB2 OQQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Zerenner","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol BS8 2PS ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"Church","sequence":"additional","affiliation":[{"name":"Department of Neurology, Royal Gwent Hospital , Newport NP20 2UB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riona","family":"Fumi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Costantini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6844-882X","authenticated-orcid":false,"given":"Edwin","family":"Jabbari","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marte T","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8071-6062","authenticated-orcid":false,"given":"Alexander","family":"Gerhard","sequence":"additional","affiliation":[{"name":"Division of Psychology Communication and Human Neuroscience, Wolfson Molecular Imaging Centre, University of Manchester , Manchester M13 9PL ,","place":["UK"]},{"name":"Departments of Nuclear Medicine, Center for Translational Neurology and Behavioral Sciences, University Medicine Essen , Essen 45147 ,","place":["Germany"]},{"name":"Department of Geriatric Medicine, Klinikum Hochsauerland , Arnsberg 59759 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6801-6194","authenticated-orcid":false,"given":"Nicola","family":"Pavese","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Newcastle University , Newcastle NE2 4HH ,","place":["UK"]},{"name":"Clinical Ageing Research Unit, Newcastle University , Newcastle NE4 6BE ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kobylecki","sequence":"additional","affiliation":[{"name":"Department of Neurology, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust , Salford M6 8HD ,","place":["UK"]},{"name":"Division of Neuroscience, School of Biological Sciences, University of Manchester , Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Nigel","family":"Leigh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Brighton and Sussex Medical School , Brighton BN1 9PX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6813-8493","authenticated-orcid":false,"given":"Ivan","family":"Koychev","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Oxford , Oxford OX3 7JX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-3774","authenticated-orcid":false,"given":"Huw R","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, University College London, Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0735-4349","authenticated-orcid":false,"given":"Sanjay G","family":"Manohar","sequence":"additional","affiliation":[{"name":"Division of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford and Oxford University Hospitals NHS Trust , Oxford OX3 9DU ,","place":["UK"]},{"name":"Nuffield Department of Clinical Neurosciences, Oxford Parkinson\u2019s Disease Centre, University of Oxford and Oxford University Hospitals NHS Trust , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"2025090219580790700_awaf132-B1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nrneurol.2017.27","article-title":"Cognitive decline in Parkinson 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