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 language | English |
|---|---|
| Pages (from-to) | 72-82 |
| Number of pages | 11 |
| Journal | Neurobiology of Aging |
| Volume | 72 |
| DOIs | |
| Publication status | Published - Dec 1 2018 |
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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 journal › Article
}
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 -