Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010
Top Cited Papers
Open Access
- 1 April 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Neuropathology and Experimental Neurology
- Vol. 71 (4), 266-273
- https://doi.org/10.1097/nen.0b013e31824b211b
Abstract
The neuropathologic examination is considered to provide the gold standard for Alzheimer disease (AD). To determine the accuracy of currently used clinical diagnostic methods, clinical and neuropathologic data from the National Alzheimers Coordinating Center, which gathers information from the network of National Institute on Aging (NIA)-sponsored Alzheimer Disease Centers (ADCs), were collected as part of the National Alzheimers Coordinating Center Uniform Data Set (UDS) between 2005 and 2010. A database search initially included all 1198 subjects with at least one UDS clinical assessment and who had died and been autopsied; 279 were excluded as being not demented or because critical data fields were missing. The final subject number was 919. Sensitivity and specificity were determined based on probable and possible AD levels of clinical confidence and 4 levels of neuropathologic confidence based on varying neuritic plaque densities and Braak neurofibrillary stages. Sensitivity ranged from 70.9% to 87.3%; specificity ranged from 44.3% to 70.8%. Sensitivity was generally increased with more permissive clinical criteria and specificity was increased with more restrictive criteria, whereas the opposite was true for neuropathologic criteria. When a clinical diagnosis was not confirmed by minimum levels of AD histopathology, the most frequent primary neuropathologic diagnoses were tangle-only dementia or argyrophilic grain disease, frontotemporal lobar degeneration, cerebrovascular disease, Lewy body disease and hippocampal sclerosis. When dementia was not clinically diagnosed as AD, 39% of these cases met or exceeded minimum threshold levels of AD histopathology. Neurologists of the NIA-ADCs had higher predictive accuracy when they diagnosed AD in subjects with dementia than when they diagnosed dementing diseases other than AD. The misdiagnosis rate should be considered when estimating subject numbers for AD studies, including clinical trials and epidemiologic studies.Keywords
This publication has 54 references indexed in Scilit:
- National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approachActa Neuropathologica, 2011
- Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective studyThe Lancet Neurology, 2011
- Genetic and Clinical Features of Progranulin-Associated Frontotemporal Lobar DegenerationArchives of Neurology, 2011
- Thinking Outside the Box: Alzheimer-Type Neuropathology That Does Not Map Directly Onto Current Consensus RecommendationsJournal of Neuropathology and Experimental Neurology, 2010
- Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascadeThe Lancet Neurology, 2010
- Modeling the Association between 43 Different Clinical and Pathological Variables and the Severity of Cognitive Impairment in a Large Autopsy Cohort of Elderly PersonsBrain Pathology, 2009
- Diagnosing Dementia: Interrater Reliability Assessment and Accuracy of the NINCDS/ADRDA Criteria versus CERAD Histopathological Criteria for Alzheimer’s DiseaseDementia and Geriatric Cognitive Disorders, 2000
- Accurate Prediction of Histologically Confirmed Alzheimer's Disease and the Differential Diagnosis of Dementia: The Use of NINCDS-ADRDA and DSM-III-R Criteria, SPECT, X-Ray CT, and Apo E4 in Medial Temporal Lobe DementiasInternational Psychogeriatrics, 1998
- Neuropathological stageing of Alzheimer-related changesActa Neuropathologica, 1991
- Clinical diagnosis of Alzheimer's diseaseNeurology, 1984