Brain disorders, including neurodegenerative diseases, and mental illnesses, are often difficult to diagnose and study due to clinical and pathological heterogeneity, overlap in clinical manifestations between disorders, and frequent comorbidities, tampering drug development and fundamental research. Hence, there is a clear need for data-driven approaches to disentangle these complex disorders. Here, we established a computational pipeline to process clinical summaries from donors with a wide range of brain disorders that were neuro-pathologically diagnosed by the Netherlands Brain Bank. First, we identified and defined 90 cross-disorder signs and symptoms within cognitive, motor, sensory, psychiatric, and general domains. Second, we trained and optimized natural language processing (NLP) models to identify these signs and symptoms in individual sentences of the extensive clinical summaries from donors of the NBB, resulting in temporal disease trajectories. Third, we studied the temporal manifestation and survival profiles across rare and complex dementias, alpha-synucleinopathies, frontotemporal dementia subtypes, and mental illnesses. Lastly, we trained a recurrent neural network to predict the Neuropathological Diagnosis. Taken together, this integrated approach resulted in a highly unique resource that can facilitate research into cross-disorder symptomatology.

The authors have declared no competing interest.

Stichting Vrienden van het Herseninstituut offered their financial support to make this work possible

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The forms and procedures of the NBB were approved by the Free University Medical Center - Medical Ethics Committee (VUmc METC, Amsterdam, the Netherlands) See also: https://www.brainbank.nl/media/uploads/file/Ethical%20declaration%202019.pdf

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Yes

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Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors