Application of Cerebrospinal Fluid AT(N) Framework on the Diagnosis of AD and Related Cognitive Disorders in Chinese Han Population

Abstract

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.

Keywords:

• Alzheimer’s disease
• cerebrospinal fluid biomarker
• AT(N)
• diagnostic confidence

Acknowledgments

We are grateful to all participants for their willingness to participate in this study.

Abbreviations

Aβ₄₂, β amyloid protein with 42 amino acids; AD, Alzheimer’s disease; CBD, cortico-basal degeneration; CSF, cerebrospinal fluid; DLB, dementia with Lewy bodies; DSM-IV, the fourth edition of Diagnostic and Statistical Manual of Mental Diseases; ELISA, enzyme linked immunosorbent assays; FTD, frontotemporal dementia; HD, Huntington’s disease; LP, lumbar puncture; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; MRI, magnetic resonance imaging; NAD, non-Alzheimer’s disease; NFTs, neurofibrillary tangles; NIA-AA, the National Institute on Aging and Alzheimer’s Association; NPH, normal pressure hydrocephalus; p-tau₁₈₁, tau phosphorylated at threonine 181; PDD, Parkinson’s disease with dementia; PNFA, progressive non-fluent aphasia; PSP, progressive supranuclear palsy; t-tau, total tau; VaD, vascular dementia.

Data Sharing Statement

The datasets generated and analyzed during the present study are available in the dementia database from Department of Neurology and Research Center of Neurology in the Second Affiliated Hospital, Zhejiang University School of Medicine.

Ethics Approval and Informed Consent

The study was approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine. Written informed consents were obtained from the patients or their caregivers. We confirm that this study was conducted in accordance with the Declaration of Helsinki.

Disclosure

All authors declare that there are no conflicts of interests.