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@ARTICLE{Vglein:285350,
author = {Vöglein, Jonathan and Arzberger, Thomas and Ebner, Irena
and Herms, Jochen and Roeber, Sigrun and Ruf, Viktoria and
Danek, Adrian and Giese, Armin and Höglinger, Günter U and
Levin, Johannes},
title = {{A}ccuracy of clinical diagnosis in neurodegenerative
diseases - a study of 455 autopsy cases.},
journal = {Journal of neurology},
volume = {273},
number = {2},
issn = {0367-004X},
address = {[Darmstadt]},
publisher = {Steinkopff},
reportid = {DZNE-2026-00216},
pages = {156},
year = {2026},
abstract = {Precision 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.Neuropathological 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.Among 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.Clinical
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.},
keywords = {Humans / Neurodegenerative Diseases: diagnosis /
Neurodegenerative Diseases: pathology / Male / Female / Aged
/ Middle Aged / Autopsy / Aged, 80 and over / Sensitivity
and Specificity / Adult / Clinical diagnosis (Other) /
Clinical–neuropathological correlation (Other) /
Diagnostic accuracy (Other) / Neurodegenerative diseases
(Other) / Neuropathology (Other)},
cin = {Clinical Research (Munich) / AG Levin / AG Herms},
ddc = {610},
cid = {I:(DE-2719)1111015 / I:(DE-2719)1111016 /
I:(DE-2719)1110001},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41721140},
pmc = {pmc:PMC12923403},
doi = {10.1007/s00415-026-13680-w},
url = {https://pub.dzne.de/record/285350},
}