Available online 8 November 2023

In both CN and MCI patients with SNAP, there was observed hippocampal atrophy.

Abnormal T or N markers result in faster cognitive and clinical decline than A-T-N-.

With identical pathology (T and N), abnormal baseline amyloid speeds decline.

Based on the 'AT(N)' system, individuals with normal amyloid biomarkers but abnormal tauopathy or neurodegeneration biomarkers are classified as non-Alzheimer's disease (AD) pathologic change. This study aimed to assess the long-term clinical and cognitive trajectories of individuals with non-AD pathologic change among older adults without dementia, comparing them to those with normal AD biomarkers and AD pathophysiology. Analyzing Alzheimer's Disease Neuroimaging Initiative data, we evaluated clinical outcomes and conversion risk longitudinally using mixed effects models and multivariate Cox proportional hazard models. We found that compared to individuals with A-T-N-, those with abnormal tauopathy or neurodegeneration biomarkers (A-T+N-, A-T-N+, and A-T+N+) had a faster rate of cognitive decline and disease progression. Individuals with A-T+N+ had a faster rate of decline than those with A-T+N-. Additionally, in individuals with the same baseline tauopathy and neurodegeneration biomarker status, the presence of baseline amyloid could accelerate cognitive decline and clinical progression. These findings provide a foundation for future studies on non-AD pathologic change and its comparison with AD pathophysiology.

Alzheimer's Disease Neuroimaging Initiative

mild cognitive impairment

magnetic resonance imaging

National Institute on Aging–Alzheimer’s Association’s

primary age-related tauopathy

Rey Auditory Verbal Learning Test

standardized uptake value ratio

non-AD pathologic change

biomarker

beta-amyloid

tau

Alzheimer

© 2023 The Author(s). Published by Elsevier Inc.