In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease

Serra, Laura, D'Amelio, Marcello, Di Domenico, Carlotta, Dipasquale, Ottavia, Marra, Camillo, Mercuri, Nicola Biagio, Caltagirone, Carlo, Cercignani, Mara and Bozzali, Marco (2018) In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease. Neurobiology of aging, 72. pp. 72-82. ISSN 1558-1497

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We assessed here functional connectivity changes in the locus coeruleus (LC) and ventral tegmental area (VTA) of patients with Alzheimer's disease (AD). We recruited 169 patients with either AD or amnestic mild cognitive impairment due to AD and 37 elderly controls who underwent cognitive and neuropsychiatric assessments and resting-state functional magnetic resonance imaging at 3T. Connectivity was assessed between LC and VTA and the rest of the brain. In amnestic mild cognitive impairment patients, VTA disconnection was predominant with parietal regions, while in AD patients, it involved the posterior nodes of the default-mode network. We also looked at the association between neuropsychiatric symptoms (assessed by the neuropsychiatric inventory) and VTA connectivity. Symptoms such as agitation, irritability, and disinhibition were associated with VTA connectivity with the parahippocampal gyrus and cerebellar vermis, while sleep and eating disorders were associated with VTA connectivity to the striatum and the insular cortex. This suggests a contribution of VTA degeneration to AD pathophysiology and to the occurrence of neuropsychiatric symptoms. We did not find evidence of LC disconnection, but this could be explained by the size of this nucleus, which makes it difficult to isolate. These results are consistent with animal findings and have potential implications for AD prognosis and therapies.

Item Type: Article
Keywords: Alzheimer's disease; VTA; LC; Brain disconnection; Neuropsychiatric symptoms
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
School of Life Sciences > Neuroscience
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
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Depositing User: Patricia Butler
Date Deposited: 31 Oct 2018 16:55
Last Modified: 02 Jul 2019 14:03

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