Michael Schöll

INTRODUCTION Cranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep‐learning–based model that produced accurate and robust cranial CT tissue classification. MATERIALS AND METHODS We analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT‐based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition. RESULTS CTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR‐based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration. DISCUSSION These findings suggest the potential future use of CT‐based volumetric measures as an informative first‐line examination tool for neurodegenerative disease diagnostics after further validation. Highlights Computed tomography (CT)–based volumetric measures can distinguish between patients with neurodegenerative disease and healthy controls, as well as between patients with prodromal dementia and controls. CT‐based volumetric measures associate well with relevant cognitive, biochemical, and neuroimaging markers of neurodegenerative diseases. Model performance, in terms of brain tissue classification, was consistent across two cohorts of diverse nature. Intermodality agreement between our automated CT‐based and established magnetic resonance (MR)–based image segmentations was stronger than the agreement between visual CT and MR imaging assessment.