Article (Scientific journals)
Metabolic connectomics targeting brain pathology in dementia with Lewy bodies.
Caminiti, Silvia P.; Tettamanti, Marco; Sala, Arianna et al.
2017In Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 37 (4), p. 1311-1325
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Keywords :
Acetylcholine/metabolism; Aged; Brain/diagnostic imaging/metabolism/pathology; Connectome/methods; Databases, Factual; Dopamine/metabolism; Energy Metabolism; Female; Fluorodeoxyglucose F18; Humans; Lewy Body Disease/diagnostic imaging/metabolism/pathology; Male; Positron-Emission Tomography/methods; Radiopharmaceuticals; Retrospective Studies; alpha-Synuclein/metabolism; Brain connectivity; graph theory; neurotransmission; sparse inverse covariance estimation; synucleinopathy
Abstract :
[en] Dementia with Lewy bodies is characterized by α-synuclein accumulation and degeneration of dopaminergic and cholinergic pathways. To gain an overview of brain systems affected by neurodegeneration, we characterized the [18F]FDG-PET metabolic connectivity in 42 dementia with Lewy bodies patients, as compared to 42 healthy controls, using sparse inverse covariance estimation method and graph theory. We performed whole-brain and anatomically driven analyses, targeting cholinergic and dopaminergic pathways, and the α-synuclein spreading. The first revealed substantial alterations in connectivity indexes, brain modularity, and hubs configuration. Namely, decreases in local metabolic connectivity within occipital cortex, thalamus, and cerebellum, and increases within frontal, temporal, parietal, and basal ganglia regions. There were also long-range disconnections among these brain regions, all supporting a disruption of the functional hierarchy characterizing the normal brain. The anatomically driven analysis revealed alterations within brain structures early affected by α-synuclein pathology, supporting Braak's early pathological staging in dementia with Lewy bodies. The dopaminergic striato-cortical pathway was severely affected, as well as the cholinergic networks, with an extensive decrease in connectivity in Ch1-Ch2, Ch5-Ch6 networks, and the lateral Ch4 capsular network significantly towards the occipital cortex. These altered patterns of metabolic connectivity unveil a new in vivo scenario for dementia with Lewy bodies underlying pathology in terms of changes in whole-brain metabolic connectivity, spreading of α-synuclein, and neurotransmission impairment.
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Caminiti, Silvia P.
Tettamanti, Marco
Sala, Arianna  ;  UniSR
Presotto, Luca
Iannaccone, Sandro
Cappa, Stefano F.
Magnani, Giuseppe
Perani, Daniela
Language :
English
Title :
Metabolic connectomics targeting brain pathology in dementia with Lewy bodies.
Publication date :
2017
Journal title :
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
ISSN :
0271-678X
eISSN :
1559-7016
Volume :
37
Issue :
4
Pages :
1311-1325
Peer reviewed :
Peer reviewed
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