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Eur J Nucl Med Mol Imaging. 2020 Feb;47(2):247-255. doi: 10.1007/s00259-019-04536-9. Epub 2019 Dec 2.

The A/T/N model applied through imaging biomarkers in a memory clinic.

Author information

1
NIMTlab, Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, 4 rue Gabrielle-Perret-Gentil, CH-1211, Geneva 14, Switzerland. alessandra.dodich@unige.ch.
2
Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
3
Cognitive Neurology Unit, Department of Neurology, Geneva University Hospitals, Geneva, Switzerland.
4
Memory Center - Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
5
Center for the Interdisciplinary Study of Gerontology and Vulnerability (CIGEV), University of Geneva, Geneva, Switzerland.
6
LANVIE - Laboratory of Neuroimaging of Aging, University of Geneva, Geneva, Switzerland.
7
LANE - Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
8
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
9
Radiology Division, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.
10
Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
11
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, Villigen-PSI, Switzerland.
12
Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
13
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
14
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
15
Neurodiagnostic and Neurointerventional Division, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.
16
Hospital for Psychogeriatric Medicine, Psychiatric University Hospital Zurich (PUK), Zurich, Switzerland.
17
NIMTlab, Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, 4 rue Gabrielle-Perret-Gentil, CH-1211, Geneva 14, Switzerland.
18
Nuclear Medicine and Molecular Imaging Division, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.

Abstract

PURPOSE:

The A/T/N model is a research framework proposed to investigate Alzheimer's disease (AD) pathological bases (i.e., amyloidosis A, neurofibrillary tangles T, and neurodegeneration N). The application of this system on clinical populations is still limited. The aim of the study is to evaluate the topography of T distribution by 18F-flortaucipir PET in relation to A and N and to describe the A/T/N status through imaging biomarkers in memory clinic patients.

METHODS:

Eighty-one patients with subjective and objective cognitive impairment were classified as A+/A- and N+/N- through amyloid PET and structural MRI. Tau deposition was compared across A/N subgroups at voxel level. T status was defined through a global cut point based on A/N subgroups and subjects were categorized following the A/T/N model.

RESULTS:

A+N+ and A+N- subgroups showed higher tau burden compared to A-N- group, with A+N- showing significant deposition limited to the medial and lateral temporal regions. Global cut point discriminated A+N+ and A+N- from A-N- subjects. On A/T/N classification, 23% of patients showed a negative biomarker profile, 58% fell within the Alzheimer's continuum, and 19% of the sample was characterized by non-AD pathologic change.

CONCLUSION:

Medial and lateral temporal regions represent a site of significant tau accumulation in A+ subjects and possibly a useful marker of early clinical changes. This is the first study in which the A/T/N model is applied using 18F-flortaucipir PET in a memory clinic population. The majority of patients showed a profile consistent with the Alzheimer's continuum, while a minor percentage showed a profile suggestive of possible other neurodegenerative diseases. These results support the applicability of the A/T/N model in clinical practice.

KEYWORDS:

18F-flortaucipir; A/T/N model; Alzheimer’s disease; PET

PMID:
31792573
DOI:
10.1007/s00259-019-04536-9

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