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The implications of different approaches to define AT(N) in Alzheimer's disease

Citation

Mattsson, Niklas (2020), The implications of different approaches to define AT(N) in Alzheimer's disease, Dryad, Dataset, https://doi.org/10.5061/dryad.p5hqbzkkx

Abstract

Objective: To compare different amyloid-β (A), tau (T) and neurodegeneration (N) [AT(N)] variants within the Swedish BioFINDER studies.

Methods: A total of490 participants were classified into AT(N) groups. These include 

53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 AD dementia) from BioFINDER-1 and 389 participants from BioFINDER-2 (245 CU and 144 CI subjects [138 MCI and six AD dementia]).Biomarkers for “A” were CSF Aβ42 and Amyloid-PET ([18F]flutemetamol); for “T” CSF P-tau and Tau-PET ([18F]flortaucipir); and for “(N)” hippocampal volume, temporal cortical thickness and CSF neurofilament light (NfL). Binarization of biomarkers was achieved using cut-offs defined in other cohorts. The relationship between different AT(N) combinations and cognitive trajectories (longitudinal Mini Mental State Examination (MMSE) scores) was examined using linear mixed modelling and coefficient of variation.

Results: Among CU subjects, A-T-(N)- or A+T-(N)- variants were most common. However, more T+ cases were seen using P-tau than Tau-PET. Among CI subjects,A+T+(N)+ was more common; however, more (N)+ cases were seen for MRI-measures relative to CSF NfL. Tau-PET best predicted longitudinal cognitive decline in CI and P-tau in CU subjects. Among CI subjects, continuous T (especially Tau-PET) and (N) measures improved the prediction of cognitive decline compared to binary measures.  

Conclusions: Our findings show that different AT(N) variants are not interchangeable, and that optimal variants differ by clinical stage. In some cases, dichotomizing biomarkers may result in loss of important prognostic information.