Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels

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J Psychiatry Neurosci 2017;42(6):366-377

Marina Weiler, PhD; Brunno Machado de Campos, PhD; Camila Vieira de Ligo Teixeira, MS; Raphael Fernandes Casseb, MS; Ana Flávia Mac Knight Carletti-Cassani, BSc; Jéssica Elias Vicentini, MS; Thamires Naela Cardoso Magalhães, MS; Leda Leme Talib, PhD; Orestes Vicente Forlenza, MD, PhD; Marcio Luiz Figueredo Balthazar, MD, PhD


Background: In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF).

Methods: We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks’ functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease.

Results: Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas.

Limitations: The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used.

Conclusion: We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

Submitted Sept. 26, 2016; Revised Nov. 30, 2016; Revised Jan. 10, 2017; Accepted Feb. 25, 2017; Early-released Apr. 4, 2017

Acknowledgements: The study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo grant #2013/10431-9.

Affiliations: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).

Competing interests: None declared.

Contributors: M. Weiler, B. de Campos and M. Balthazar designed the study. M. Weiler, C. Teixeira, A. Carletti-Cassani, J. Vicentini and T. Magalhães acquired the data, which M. Weiler, B. de Campos, R. Casseb, L. Talib, O. Forlenza and M. Balthazar analyzed. M. Weiler, B. de Campos, R. Casseb, A. Carletti-Cassani, J. Vicentini, T. Magalhães and L. Talib wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.160190

Correspondence to: M. Weiler, Neuroimaging Laboratory, Hospital de Clínicas da Unicamp Rua Vital Brasil, 251 Cidade Universitária Zeferino Vaz, Campinas – SP – Brasil;