In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer’s disease
Open accessAbstract
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.
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Our data confirm the very recent clinical evidence from MCI and AD patients showing that functional, structural and metabolic changes affecting the VTA and its projection areas in the mesocorticolimbic pathway occur at the earlier stages of the disease.
“Our data confirm the very recent clinical evidence from MCI and AD patients showing that functional, structural and metabolic changes affecting the VTA and its projection areas in the mesocorticolimbic pathway occur at the earlier stages of the disease (De Marco and Ven neri, 2018; Iaccarino et al., 2020; Serra et al., 2018).”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Serra et al., 2018
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References 66 · Cited by 91
- Authors
- Serra, L., D'Amelio, M., Di Domenico, C., Dipasquale, O., Marra, C., Mercuri, N. B., Caltagirone, C., Cercignani, M., & Bozzali, M.
- Affiliations
- Fondazione Santa Lucia (IT)
- King's College London (GB)
- Università Cattolica del Sacro Cuore (IT)
- University of Rome Tor Vergata (IT)
- Brighton and Sussex Medical School (GB)
- Corresponding author
- Bozzali, Marco
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 72
- Pages
- 72-82
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2888617722
- Cited by
- 91
- References
- 66
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 15 · 2023: 7 · 2022: 16 · 2021: 15 · 2020: 15 · 2019: 4
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by-nc-nd)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, cc-by-nc-nd)
- Figshare (submittedVersion, cc-by-nc-nd)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Funders
- Italian Ministry of Health (GR-2011-02351457)
- Alzheimer's Association, United States (AARG-18-566270s)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, amnestic mild cognitive impairment, locus coeruleus, ventral tegmental area, functional connectivity, brainstem, default mode network, neuropsychiatric symptoms, resting-state functional connectivity, parahippocampal gyrus, cerebellar vermis, striatum, insula
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amnesia, Behavioral Symptoms, Brain Mapping, Cerebral Cortex, Corpus Striatum, Female, Humans, Locus Coeruleus, Magnetic Resonance Imaging, Male, Nerve Net, Ventral Tegmental Area, Cognitive Dysfunction, Cerebellar Vermis
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