Optimal ATN biomarkers and their role in predicting cognitive progress of mild cognitive impairment

Abstract Background It is of great significance to investigate the optimal cerebrospinal fluid (CSF) and magnetic resonance image biomarkers of ATN system and clarify their predictive value in cognitive progression of mild cognitive impairment individuals (MCI). Methods 147 healthy control (HC), 197 patients with MCI, and 128 patients with Alzheimer’ Disease (AD) were included from the ADNI database. All MCI patients were followed up from 6 to 60 months. The amyloid (A) was assessed by CSF Aβ42 or Aβ42/Aβ40. The tau pathology (T) was assessed by CSF p-tau. The neurodegeneration (N) was assessed by radiomics of the whole brain MRI or by CSF t-tau. Biomarkers with larger area under the receiver operating characteristic curve (AUC) in the discrimination of AD and HC were considered to be the optimal biomarkers. The conversion rates of different ATN profiles in MCI subjects during follow-up were analyzed using Kaplan-Meier estimates and compared using the Log-rank test. Results The CSF Aβ 42 and the radiomics signature (AUC 0.822 and 0.998, respectively) were identified as the optimal A and N biomarkers, respectively. For MCI patients of the Alzheimer continuum, there was no significant difference in the progression rate of A + T − N− and A − T−N − profiles (p > 0.05). The A + T + N−, A + T − N + profiles had a significant higher progression rate than that of the A + T − N− patients (all p < 0.05). For MCI of the suspected non-AD pathophysiology (SNAP), patients with the A − T−N + profile (p < 0.05) showed significant higher progression rate than A − T−N − profile. There was no significant difference in the progression rate of A − T + N − and A − T−N − profiles (p > 0.05). Discussion We proposed a new radiomics method to assess N accurately and ascertained the optimal A/T/N biomarkers for the discrimination of HC and AD. For MCI patients of the Alzheimer continuum, isolated A + was indicator of cognitive stability, while the abnormality of T and N, respectively or simultaneously, indicated the high risk of progression. For MCI patients of SNAP, isolated T + indicated the cognitive stability, while the appearance of N + indicated the high risk of progression.