Challenges associated with biomarker‐based classification systems for Alzheimer's disease

• Main Authors: Ignacio Illán‐Gala, Jordi Pegueroles, Victor Montal, Eduard Vilaplana, María Carmona‐Iragui, Daniel Alcolea, Bradford C. Dickerson, Raquel Sánchez‐Valle, Mony J. deLeon, Rafael Blesa, Alberto Lleó, Juan Fortea, Alzheimer's Disease Neuroimaging Initiative
• Format: Article
• Language: English
• Published: Wiley 2018-01-01
• Series: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
• Subjects: Alzheimer's disease; Biomarkers; Magnetic resonance; Positron emission tomography; Classification systems; Diagnosis
• Online Access: https://doi.org/10.1016/j.dadm.2018.03.004

Abstract Introduction We aimed to evaluate the consistency of the A/T/N classification system. Methods We included healthy controls, mild cognitive impairment, and dementia patients from Alzheimer's disease Neuroimaging Initiative. We assessed subject classification consistency with different biomarker combinations and the agreement and correlation between biomarkers. Results Subject classification discordance ranged from 12.2% to 44.5% in the whole sample; 17.3%–46.4% in healthy controls; 11.9%–46.5% in mild cognitive impairment, and 1%–35.7% in dementia patients. Amyloid, but not neurodegeneration biomarkers, showed good agreement both in the whole sample and in the clinical subgroups. Amyloid biomarkers were correlated in the whole sample, but not along the Alzheimer's disease continuum (as defined by a positive amyloid positron emission tomography). Neurodegeneration biomarkers were poorly correlated both in the whole sample and along the Alzheimer's disease continuum. The relationship between biomarkers was stage‐dependent. Discussion Our findings suggest that the current A/T/N classification system does not achieve the required consistency to be used in the clinical setting.