A new article from the EPAD consortium entitled “Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort” has recently been published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
In this article, the ATN classification was operationalized in the first 1500 participants consented in the EPAD cohort (V1500.0), a deeply phenotyped cohort of individuals who do not have dementia. CSF biomarkers were used for A and T staging, and MRI biomarkers (age-adjusted hippocampal volume) for N as they showed that t-tau is not appropriate for describing neurodegeneration in populations without dementia. The authors further examined the neuropsychological and radiological profiles of the different ATN stages, finding that cognitive dysfunction, especially in the memory domain, appears with p-tau. The authors demonstrated that bi-directional regional volumetric changes are observed in the brain of individuals early along the ATN continuum and that cerebrovascular burden increases with biomarkers positivity along the Alzheimer’s disease continuum.
Congratulations to the authors! You can read the paper here.
The ATN classification has been added for public use to the analytical database of the EPAD Longitudinal Cohort Study (LCS), hosted by our partner Aridhia. This analytical database includes all of the clinical, cognitive and biomarker measurements of recruited participants according to the EPAD LCS protocol, collected and curated according to high quality standards. EPAD has made this database open access and publicly available to the research community through the EPAD LCS Research Access Process (ERAP). To access to it, please visit the EPAD website here.
Background: We classified non‐demented European Prevention of Alzheimer’s Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles. Materials and methods: From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut‐offs of 1000 pg/mL for amyloid beta (Aß)1‐42 and 27 pg/mL for p‐tau181 were validated using Gaussian mixture models. Given strong correlation of p‐tau and t‐tau (R2 = 0.98, P < 0.001), neurodegeneration was defined by age‐adjusted hippocampal volume. Multinomial regressions were used to test whether neuropsychological tests and regional brain volumes could distinguish ATN stages. Results: Age was 65 ± 7 years, with 58% females and 38% apolipoprotein E (APOE) ε4 carriers; 57.1% were A–T–N–, 32.5% were in the Alzheimer's disease (AD) continuum, and 10.4% suspected non‐Alzheimer's pathology. Age and cerebrovascular burden progressed with biomarker positivity (P < 0.001). Cognitive dysfunction appeared with T+. Paradoxically higher regional gray matter volumes were observed in A+T–N– compared to A–T–N– (P < 0.001). Discussion: In non‐demented individuals along the AD continuum, p‐tau drives cognitive dysfunction. Memory and language domains are affected in the earliest stages.