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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2018

Open Access 01-12-2018 | Research

A biomarker study in long-lasting amnestic mild cognitive impairment

Authors: Chiara Cerami, Alessandra Dodich, Sandro Iannaccone, Giuseppe Magnani, Roberto Santangelo, Luca Presotto, Alessandra Marcone, Luigi Gianolli, Stefano F. Cappa, Daniela Perani

Published in: Alzheimer's Research & Therapy | Issue 1/2018

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Abstract

Background

Mild cognitive impairment (MCI) is a heterogeneous syndrome resulting from Alzheimer’s disease (AD) as well as to non-AD and non-neurodegenerative conditions. A subset of patients with amnestic MCI (aMCI) present with an unusually long-lasting course, a slow rate of clinical neuropsychological progression, and evidence of focal involvement of medial temporal lobe structures. In the present study, we explored positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a sample of subjects with aMCI with such clinical features in order to provide in vivo evidence to improve disease characterisation in this subgroup.

Methods

Thirty consecutive subjects with aMCI who had long-lasting memory impairment (more than 4 years from symptom onset) and a very slow rate of cognitive progression were included. All subjects underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) metabolic imaging. A measure of cerebral amyloid load, by PET and/or CSF, was obtained in 26 of 30 subjects. The mean clinical follow-up was 58.3 ± 10.1 months.

Results

No patient progressed to dementia during the follow-up. The typical AD FDG-PET pattern of temporoparietal hypometabolism was not present in any of the subjects. In contrast, a selective medial temporal lobe hypometabolism was present in all subjects, with an extension to frontolimbic regions in some subjects. PET imaging showed absent or low amyloid load in the majority of samples. The values were well below those reported in prodromal AD, and they were slightly elevated in only two subjects, consistent with the CSF β-amyloid (1–42) protein values. Notably, no amyloid load was present in the hippocampal structures.

Conclusions

FDG-PET and amyloid-PET together with CSF findings questioned AD pathology as a unique neuropathological substrate in this aMCI subgroup with long-lasting disease course. The possibility of alternative pathological conditions, such as argyrophilic grain disease, primary age-related tauopathy or age-related TDP-43 proteinopathy, known to spread throughout the medial temporal lobe and limbic system structures should be considered in these patients with MCI.
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Metadata
Title
A biomarker study in long-lasting amnestic mild cognitive impairment
Authors
Chiara Cerami
Alessandra Dodich
Sandro Iannaccone
Giuseppe Magnani
Roberto Santangelo
Luca Presotto
Alessandra Marcone
Luigi Gianolli
Stefano F. Cappa
Daniela Perani
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2018
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-018-0369-8

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