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Alzheimers Res Ther. 2019 Jan 31;11(1):15. doi: 10.1186/s13195-019-0466-3.

Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study.

Author information

1
Department of Psychosomatic Medicine, Clinical Dementia Research, Faculty of Medicine, Rostock University, Rostock, Germany. fatemah.sakr@med.uni-rostock.de.
2
German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany. fatemah.sakr@med.uni-rostock.de.
3
German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
4
AXA Research Fund and Sorbonne University Chair, Paris, France.
5
Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, F-75013, Paris, France.
6
Brain and Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, F-75013, Paris, France.
7
Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, F-75013, Paris, France.
8
Qynapse, Paris, France.
9
Sorbonne University, UPMC University Paris 06, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, F-75013, Paris, France.
10
Multi-center Neuroimaging Platform.
11
Department of Nuclear Medicine, Pitié-Salpêtrière Hospital, AP-HP, F-75013, Paris, France.
12
Department of Neurology, University Medical Center of the Johannes-Gutenberg-University Mainz, Langenbeck str, 155131, Mainz, Germany.
13
Centre de NeuroImagerie de Recherche (CENIR), Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France.
14
Department of Neuroradiology, Salpêtriere Hospital, Paris, France.
15
Department of Psychosomatic Medicine, Clinical Dementia Research, Faculty of Medicine, Rostock University, Rostock, Germany.

Abstract

BACKGROUND:

Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer's disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual's amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer's disease (AD).

METHODS:

The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models.

RESULTS:

In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVRCereb = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort.

CONCLUSIONS:

The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD.

KEYWORDS:

Amyloid PET; In vivo staging; Subjective memory complaint

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