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Applying the ATN scheme in a memory clinic population: The ABIDE project
Daniele Altomare1, Arno de Wilde1, Rik Ossenkoppele1
1From the Alzheimer Center Amsterdam, Department of Neurology (D.A., A.d.W., R.O., W.P., F.B., C.G., I.v.M., M.Z., B.N.v.B., P.S., W.M.v.d.F.), Department of Radiology & Nuclear Medicine (R.O., C.G., M.Y., F.B., B.N.v.B.), and Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology & Biostatistics (I.v.M., W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; Laboratory of Neuroimaging of Aging (LANVIE) (D.A., G.B.F.), University of Geneva, Switzerland; Memory Clinic (D.A.), University Hospitals of Geneva, Switzerland; Laboratory of Alzheimer's Neuroimaging and Epidemiology (LANE) (D.A.), Saint John of God Clinical Research Centre; Department of Molecular and Translational Medicine (D.A.), University of Brescia, Italy; Clinical Memory Research Unit (R.O.), Lund University, Malmö, Sweden; Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK; and Memory Clinic (D.A., G.B.F.), University Hospitals of Geneva, Switzerland.
The ATN biomarker scheme effectively categorizes memory clinic patients, revealing distinct profiles linked to cognitive decline. This approach aids in understanding Alzheimer's disease progression and patient stratification.
Area of Science:
- Neurology
- Biomarker Research
- Cognitive Neuroscience
Background:
- The Amyloid-Tau-Neurodegeneration (ATN) classification system is a framework for neurodegenerative disease research.
- Applying the ATN scheme to memory clinic populations can help differentiate patient groups based on specific pathological features.
Purpose of the Study:
- To implement the ATN biomarker scheme in a memory clinic setting.
- To evaluate if the ATN scheme can distinguish patient subgroups with unique demographic, clinical, and cognitive characteristics.
- To analyze cognitive decline trajectories across different ATN profiles.
Main Methods:
- 305 memory clinic patients were classified using amyloid PET ([18F]Florbetaben), CSF p-tau, and medial temporal lobe atrophy.
- Patients were categorized into subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia groups.
- Demographic, clinical, cognitive features, and longitudinal cognitive changes were assessed for each ATN profile.
Main Results:
- The proportion of amyloid-positive, tau-positive, and neurodegeneration-positive (A+T+N+) patients increased with disease severity (1% in SCD to 35% in dementia).
- Alzheimer's disease profiles (A+T+N- and A+T+N+) were associated with older age, higher APOE ε4 prevalence, and poorer baseline cognitive function (MMSE, memory, visuospatial).
- Non-Alzheimer profiles showed distinct patterns, including more white matter hyperintensities and worse language performance. Faster cognitive decline was observed in A+T+N- and A+T+N+ profiles, particularly in non-demented patients.
Conclusions:
- The ATN scheme successfully identified distinct biomarker profiles within a memory clinic cohort.
- These profiles exhibited overlapping baseline characteristics but varied patterns of cognitive decline.
- The complexity and number of ATN profiles present challenges for clinical application, especially regarding implications for patients with and without dementia.
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