Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Feb;46(2):288-296.
doi: 10.1007/s00259-018-4149-2. Epub 2018 Sep 22.

Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer's disease in mild cognitive impairment patients

Andrea Ciarmiello  1 , Antonio Tartaglione  2 , Elisabetta Giovannini  3 , Mattia Riondato  3 , Giampiero Giovacchini  3 , Ornella Ferrando  4 , Marina De Biasi  2 , Chiara Passera  2 , Elena Carabelli  5 , Antonio Mannironi  5 , Franca Foppiano  4 , Bruno Alfano  6 , Luigi Mansi  7
Affiliations

Amyloid burden identifies neuropsychological phenotypes at increased risk of progression to Alzheimer's disease in mild cognitive impairment patients

Andrea Ciarmiello et al. Eur J Nucl Med Mol Imaging. 2019 Feb.

Abstract

Purpose: The extent of amyloid burden associated with cognitive impairment in amnestic mild cognitive impairment is unknown. The primary aim of the study was to determine the extent to which amyloid burden is associated to the cognitive impairment. The secondary objective was to test the relationship between amyloid accumulation and memory or cognitive impairment.

Materials and methods: In this prospective study 66 participants with amnestic mild cognitive impairment underwent clinical, neuropsychological and PET amyloid imaging tests. Composite scores assessing memory and non-memory domains were used to identify two clinical classes of neuropsychological phenotypes expressing different degree of cognitive impairment. Detection of amyloid status and definition of optimal amyloid ± cutoff for discrimination relied on unsupervised k-means clustering method.

Results: Threshold for identifying low and high amyloid retention groups was of SUVr = 1.3. Aß + participants showed poorer global cognitive and episodic memory performance than subjects with low amyloid deposition. Aß positivity significantly identified individuals with episodic memory impairment with a sensitivity and specificity of 80 and 79%, (χ2 = 21.48; P < 0.00001). Positive and negative predictive values were 82 and 76%, respectively. Amyloid deposition increased linearly as function of memory impairment with a rate of 0.13/ point of composite memory score (R = -44, P = 0.0003).

Conclusion: The amyloid burden of SUVr = 1.3 allows early identification of subjects with episodic memory impairment which might predict progression from MCI to Alzheimer's disease.

Trial registration: EudraCT 2015-001184-39.

Keywords: Beta-amyloid; Cognitive trajectory; Memory performance; Mild cognitive impairment; PET imaging.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Axial view of [18F]Florbetaben PET amyloid load in mild cognitive impairment. Average axial slices of mild cognitive impairment subjects with low (Aß-; top panel) and high amyloid load (Aß+; bottom panel). Subjects were classified using k-means clustering. Signal intensity is significantly lower in the grey matter regions of the top images compared to those of the bottom images (P < 0.0001)
Fig. 2
Fig. 2
Distribution of individual SUVR values as function of composite score for episodic memory (panel a) and non-memory domain (panel b). Aβ- and Aβ + MCI subjects are showed as light blue and red circles, respectively. Regression line is showed in red. The black dashed line represents the SUVR cutoff of 1.3 discriminating subjects with high and low tracer retention. The vertical red dashed line represents the 10th percentile of individuals with positive composite score for memory and non-memory cognition tests. Shaded area represents confidence interval of the fit. Aβ = amyloid β. EMCs = episodic memory composite score. NMCs = non-memory composite score. MCI = mild cognitive impairment
See this image and copyright information in PMC

References

    1. Petersen RC. Early diagnosis of Alzheimer’s disease: is MCI too late? Curr Alzheimer Res. 2009;6:324–330. doi: 10.2174/156720509788929237. - DOI - PMC - PubMed
    1. AmericanPsychiatricAssociation . Diagnostic and statistical manual of mental disorders. Washington, DC: American Psychiatric Association; 2013.
    1. Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014;275:214–228. doi: 10.1111/joim.12190. - DOI - PMC - PubMed
    1. Jack CR, Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9:119–128. doi: 10.1016/S1474-4422(09)70299-6. - DOI - PMC - PubMed
    1. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367:795–804. doi: 10.1056/NEJMoa1202753. - DOI - PMC - PubMed