Accuracy of clinical diagnosis in neurodegenerative diseases - a study of 455 autopsy cases.

backgroundPrecision of clinical diagnosis in neurodegenerative diseases is critically important for clinical care and study recruitment. This study aimed to investigate the clinical accuracy using gold-standard neuropathological reference.

methodsNeuropathological diagnoses from the Neurobiobank München were correlated with real-world clinical diagnoses from hospitals in Germany. Accuracy metrics, including sensitivity, specificity, and area under the curve (AUC) of clinical diagnoses, were calculated.

resultsAmong nine neuropathologically diagnosed neurodegenerative diseases (Alzheimer's disease, argyrophilic grain disease, corticobasal degeneration, frontotemporal lobar degeneration, Huntington's disease, Lewy body disease, motor neuron disease, multiple system atrophy, and progressive supranuclear palsy) with a total of 455 cases, clinical sensitivity varied widely (0-100%) whereas specificity was consistently high (89.5-100%). Accuracy was very good (AUC > 0.9) for Huntington's disease, motor neuron disease, and multiple system atrophy; good (AUC = 0.8-0.9) for Alzheimer's disease, dementia with Lewy bodies/Parkinson's disease, and progressive supranuclear palsy; moderate (AUC = 0.7-0.8) for frontotemporal dementia, limited (AUC = 0.51-0.7) in the n = 20 cases with corticobasal degeneration, and no discriminatory capacity (AUC = 0.5) in the n = 6 cases with argyrophilic grain disease.

conclusionsClinical diagnostic accuracy of neurodegenerative diseases varies, with sensitivity as the main limiting factor. Improving diagnostic sensitivity will be essential for early and accurate patient identification, especially as disease-modifying therapies targeting causal proteinopathies become available. Achieving this will depend on the development and clinical implementation of reliable molecular biomarkers that indicate the causal proteinopathies of neurodegenerative diseases.