De Marco, M. and Venneri, A. (2018) Volume and Connectivity of the Ventral Tegmental Area are Linked to Neurocognitive Signatures of Alzheimer's Disease in Humans. Journal of Alzheimer's disease, 63 (1). pp. 167-180. ISSN 1387-2877
Abstract
Background: There is an urgent need to identify the earliest biological changes within the neuropathological cascade of Alzheimer’s disease (AD) processes. Recent findings in a murine model of AD showed significant preclinical loss of dopaminergic neurons in the ventral tegmental area (VTA), accompanied by reduced hippocampal innervation and declining memory. It is unknown if these observations can be translated in humans.
Objective: We tested the hypothesis that VTA volume is associated with the typical clinical markers of AD in a cohort of patients and healthy controls.
Methods: Structural and resting state functional MRI scans, and neuropsychological scores were acquired for 51 healthy adults, 30 patients with a diagnosis of mild cognitive impairment, and 29 patients with a diagnosis of AD dementia. VTA volume was quantified together with other control nuclei. The association between nuclei volume, hippocampal size, memory performance, and linguistic-executive skills was tested. The effect of VTA functional connectivity was also tested.
Results: VTA size, but not of control nuclei, yielded a strong association with both hippocampal size and memory competence (but not linguistic-executive performance), and this was particularly strong in healthy adults. In addition, functional connectivity between the VTA and hippocampus was significantly associated with both markers of AD. Conclusion: Diminished dopaminergic VTA activity may be crucial for the earliest pathological features of AD and might suggest new strategies for early treatment. Memory encoding processes may represent cognitive operations susceptible to VTA neurodegeneration.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 IOS Press. This is an author produced version of a paper subsequently published in Journal of Alzheimer's Disease. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Alzheimer Disease (D000544); Dopaminergic Neurons (D059290); Gray Matter (D066128); Functional Neuroimaging (D059907); Neuroimaging (D059906); Early Diagnosis (D042241); Memory, (D008568); Cognitive Dysfunction/Mild Cognitive Impairment (D060825); Hippocampus (D006624); Tegmentum Mesencephali/Ventral Tegmental Nucleus (D013681) |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Mar 2018 15:59 |
Last Modified: | 14 May 2018 10:49 |
Published Version: | https://doi.org/10.3233/JAD-171018 |
Status: | Published |
Publisher: | IOS Press |
Refereed: | Yes |
Identification Number: | 10.3233/JAD-171018 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:128704 |