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Application of Cerebrospinal Fluid AT(N) Framework on the Diagnosis of AD and Related Cognitive Disorders in Chinese
Ling-Qi Ye1,2, Pei-Rong Gao1, Yan-Bin Zhang1,3
1Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Insights
The AT(N) framework using cerebrospinal fluid biomarkers aids Alzheimer's disease (AD) diagnosis in Chinese patients. Amyloid positivity improves AD diagnosis and confidence, while amyloid negativity can decrease diagnostic certainty.
Area of Science:
- Neurology
- Biomarker Research
- Neurodegenerative Diseases
Background:
- Limited studies explore the AT(N) framework's diagnostic impact in dementia.
- The AT(N) framework assesses Alzheimer's disease (AD) using cerebrospinal fluid (CSF) biomarkers: amyloid-beta 42, total tau, and phosphorylated tau 181.
- This study addresses the diagnostic application of the AT(N) framework in Chinese Han population.
Purpose of the Study:
- To evaluate the clinical utility of the CSF AT(N) framework for diagnosing Alzheimer's disease (AD).
- To assess its role in the differential diagnosis of cognitive disorders.
- To quantify the impact of CSF biomarkers on diagnostic confidence in a Chinese cohort.
Main Methods:
- 137 patients with cognitive disorders underwent CSF analysis for Aβ42, t-tau, and p-tau181.
- CSF biomarker results were interpreted using the AT(N) framework.
- Neurologists provided diagnoses and confidence levels pre- and post-biomarker disclosure.
Main Results:
- CSF biomarkers led to a 28% change in initial diagnoses.
- Amyloid positivity (A+) correlated with confirmed AD diagnoses and increased confidence (+17.5%).
- Amyloid negativity (A-) with or without tau pathology sometimes decreased diagnostic confidence.
Conclusions:
- The AT(N) framework, particularly amyloid status, is valuable for AD diagnosis and improving clinician confidence.
- Negative amyloid pathology results can introduce diagnostic uncertainty for primary AD.
- This is the first quantitative study on the CSF AT(N) framework's clinical capability in the Chinese Han population with cognitive disorders.
Background:
Studies concerning the impact of the AT(N) framework on diagnostic capability in the dementia population are lacking. We aimed to explore the diagnostic application of CSF AT(N) framework in clinical routines of Alzheimer's disease (AD) as well as differential diagnosis of other cognitive diseases in the Chinese Han population.
Patients And Methods:
A total of 137 patients with cognitive disorders received CSF tests of Aβ42, t-tau and p-tau181. Their CSF biomarker results were categorized and interpreted by the AT(N) framework. Neurologists provided a diagnosis both pre- and post-CSF biomarker disclosure with corresponding diagnostic confidence.
Results:
The total initial diagnosis included 79 patients with AD and 58 patients with non-AD (NAD). The results of CSF biomarkers led to a diagnostic change of 28% in the cohort. Approximately 81.5% (n=53) of 65 patients whose CSF biomarker showed an underlying AD pathology were finally diagnosed as AD, with an increase of 17.5% in diagnostic confidence. Thirty-seven CSF results indicating NAD pathologic changes contributed to an exclusion of AD in 56.8% (n=21) of the patients along with a modest increase of 9.8% in average confidence. Thirty-five patients with normal CSF biomarkers maintained the diagnosis of NAD in 68.6% (n=24) of the group, leading to a slight elevation of 7.6% in confidence.
Conclusion:
We found that the presence of amyloid pathology (A+) is contributable to diagnosing AD and improving confidence. On occasion of negative amyloid pathology (A-), with or without tau pathology, gaining uncertainty of the primary AD diagnosis would diminish the corresponding confidence. To the best of our knowledge, this is the first study performed in the Chinese Han population with cognitive disorders that explores the clinical capability of CSF AT(N) framework in a quantitative way.
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