Disrupted metabolic connectivity in dopaminergic and cholinergic networks at different stages of dementia from (18)F-FDG PET brain persistent homology network.

Affiliation

Hsu TW(1)(2), Fuh JL(#)(3)(4)(5), Wang DW(6), Chen LF(7), Chang CJ(2)(8), Huang WS(2)(8), Wu HM(#)(9)(10), Guo WY(1)(11).
Author information:
(1)Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 11217, Taiwan.
(2)Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
(3)Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. [Email]
(4)Division of General Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 11217, Taiwan. [Email]
(5)Brain Research Center, National Yang-Ming University, Taipei, Taiwan. [Email]
(6)Institute of Information Science, Academia Sinica, Taipei, Taiwan.
(7)Institute of Brain Science, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
(8)Integrated PET/MR Imaging Center, Taipei Veterans General Hospital, Taipei, Taiwan.
(9)Department of Radiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 11217, Taiwan. [Email]
(10)Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. [Email]
(11)Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
(#)Contributed equally

Abstract

Dementia is related to the cellular accumulation of β-amyloid plaques, tau aggregates, or α-synuclein aggregates, or to neurotransmitter deficiencies in the dopaminergic and cholinergic pathways. Cellular and neurochemical changes are both involved in dementia pathology. However, the role of dopaminergic and cholinergic networks in metabolic connectivity at different stages of dementia remains unclear. The altered network organisation of the human brain characteristic of many neuropsychiatric and neurodegenerative disorders can be detected using persistent homology network (PHN) analysis and algebraic topology. We used 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging data to construct dopaminergic and cholinergic metabolism networks, and used PHN analysis to track the evolution of these networks in patients with different stages of dementia. The sums of the network distances revealed significant differences between the network connectivity evident in the Alzheimer's disease and mild cognitive impairment cohorts. A larger distance between brain regions can indicate poorer efficiency in the integration of information. PHN analysis revealed the structural properties of and changes in the dopaminergic and cholinergic metabolism networks in patients with different stages of dementia at a range of thresholds. This method was thus able to identify dysregulation of dopaminergic and cholinergic networks in the pathology of dementia.