ATN Classification and Clinical Progression of the Amyloid-Negative Group in Alzheimer’s Disease Neuroimaging Initiative Participants

Abstract

Alzheimer's disease has recently been classified using three biological markers (amyloid [A], tau [T], and neurodegeneration [N]) to help elucidate its progression. We aimed to investigate whether there were differences between cognitive function and the clinical dementia symptoms over time relative to the ATN classification in the amy-loid-negative group. In the Alzheimer's Disease Neuroimaging Initiative (ADNI) co-hort, 310 participants who underwent all the tests required for ATN classification were enrolled. The cognitive function score differences (Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 [ADAS-Cog 13], Clinical Dementia Rating Sum of Boxes [CDR-SOB], and Mini-Mental State Examination [MMSE]) between the groups were analyzed using the analysis of covariance and score changes over time with a linear mixed-effects model. In the cross-sectional analysis, ADAS-Cog 13 scores were higher for AT -N+ and A-T+N+ than for AT -N-(p＜0.001) and A-T+N-(p＜0.001). In the longitudinal analysis, CDR-SOB scores for A-T+N+ deteriorated faster than AT -N-(p＜ 0.001), A-T+N-(p＜0.001) and AT -N+ (p＜0.001). Hippocampal atrophy progressed faster in AT -N+ (p＜0.001) and A-T+N+ (p=0.02) than in AT -N-. Through this study, we discovered that even in individuals classified as amyloid negative, neurodegene-ration with tau deposition exacerbates cognitive decline and worsens clinical symptoms , underscoring the need for continuous monitoring and observation.