Association of structural MRI with Braak staging using neural network‐based risk scoring

Abstract Background The gold standard of Alzheimer’s disease (AD) diagnosis remains histopathologic examination of neuropathologic changes. However, the dependence on post‐mortem microscopic analysis limits the role of pathology in clinical care. Magnetic resonance imaging (MRI) is routinely used to diagnose suspected dementia (DE) due to AD, but correlating neuroimaging to underlying pathologic changes remains challenging. Herein, we report the development of two risk scores derived from convolutional neural network (CNN) processing of MRI scans, which we then validate against Braak staging of neurofibrillary tangles from autopsy reports. Method Using T1‐weighted MRIs from the National Alzheimer’s Coordinating Center (NACC), we trained two CNNs (Figure 1) to predict continuous scores for overall cognitive status (“COG” score) and AD probability (“ALZ” score). The COG score, ranging from 0‐2, graded a subject’s cognitive status on a spectrum from normal cognition (NC, 0), to mild cognitive impairment (MCI, 1), and DE due to any cause (2). The ALZ score then graded each DE individual’s probability of AD from 0 to 1. These CNNs were then applied to a subset of participants with autopsy reports available within 6 months of MRI. CNN performance was evaluated by area under receiver operating characteristic curve (AUC). Differences in risk scores were assessed by Kruskal‐Wallis H testing with post hoc Dunn testing. Result The CNN models for COG and ALZ score estimation were trained on 4,822 NACC participants. Thresholding of COG scores distinguished individuals with DE from those with NC and MCI (AUC = 0.87). ALZ scores distinguished individuals with AD from those with non‐AD causes of DE (AUC = 0.77). Among 74 persons with available neuropathology data, COG scores differed significantly among Braak staging groups (p<0.001), increasing from a mean of 0.99±0.36 in Stage 1 to 1.47±0.41 in Stage 6 (p = 0.010). Significant differences in ALZ scores were also observed (p = 0.039) between varying Braak stages (p = 0.039), increasing from a mean of 0.69±0.42 in Stage 1 to 0.91±0.29 in Stage 6 (p = 0.046) (Figure 2) . Conclusion CNN processing of MRI scans may derive continuous risk scores for grading cognitive status and AD risk. This novel approach may offer practitioners a computational tool to improve AD diagnosis.