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

Laura Serra, Marcello D'Amelio, Carlotta Di Domenico, Ottavia Dipasquale, Camillo Marra, Nicola Biagio Mercuri, Carlo Caltagirone, Mara Cercignani, Marco Bozzali

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)72-82
Number of pages11
JournalNeurobiology of Aging
Volume72
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Ventral Tegmental Area
Brain Stem
Alzheimer Disease
Locus Coeruleus
Parahippocampal Gyrus
Parietal Lobe
Cerebral Cortex
Magnetic Resonance Imaging
Equipment and Supplies
Brain

Keywords

  • Alzheimer's disease
  • Brain disconnection
  • LC
  • Neuropsychiatric symptoms
  • VTA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

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; Bozzali, Marco.

In: Neurobiology of Aging, Vol. 72, 01.12.2018, p. 72-82.

Research output: Contribution to journalArticle

@article{cd265298612c4fd79fd5ca1fbd3d0579,
title = "In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease",
abstract = "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.",
keywords = "Alzheimer's disease, Brain disconnection, LC, Neuropsychiatric symptoms, VTA",
author = "Laura Serra and Marcello D'Amelio and {Di Domenico}, Carlotta and Ottavia Dipasquale and Camillo Marra and Mercuri, {Nicola Biagio} and Carlo Caltagirone and Mara Cercignani and Marco Bozzali",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/j.neurobiolaging.2018.08.012",
language = "English",
volume = "72",
pages = "72--82",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease

AU - Serra, Laura

AU - D'Amelio, Marcello

AU - Di Domenico, Carlotta

AU - Dipasquale, Ottavia

AU - Marra, Camillo

AU - Mercuri, Nicola Biagio

AU - Caltagirone, Carlo

AU - Cercignani, Mara

AU - Bozzali, Marco

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Brain disconnection

KW - LC

KW - Neuropsychiatric symptoms

KW - VTA

UR - http://www.scopus.com/inward/record.url?scp=85053406755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053406755&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2018.08.012

DO - 10.1016/j.neurobiolaging.2018.08.012

M3 - Article

AN - SCOPUS:85053406755

VL - 72

SP - 72

EP - 82

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -