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

Author(s)

Weiler, Marina ^[1] ; de Campos, Brunno Machado ^[1] ; de Ligo Teixeira, Camila Vieira ^[1] ; Casseb, Raphael Fernandes ^[1] ; Mac Knight Carletti-Cassani, Ana Flavia ^[1] ; Vicentini, Jessica Elias ^[1] ; Cardoso Magalhaes, Thamires Naela ^[1] ; Talib, Leda Leme ^{[2, 3]} ; Forlenza, Orestes Vicente ^{[2, 3]} ; Figueredo Balthazar, Marcio Luiz ^[1]

Affiliation

^[1] Univ Estadual Campinas, Neuroimaging Lab, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Lab Neurosci, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept & Inst Psychiat, Fac Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF PSYCHIATRY & NEUROSCIENCE; v. 42, n. 6, p. 366-377, NOV 2017.
• Web of Science Citations: 3

Abstract

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. (AU)

• FAPESP's process: 13/10431-9 - Anatomical and functional connectivity in Default Mode and Salience Networks in mild dementia of Alzheimer's Disease and amnestic mild cognitive impairment
• Grantee: Marina Weiler
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)