TY  - JOUR
AU  - Liebe, Thomas
AU  - Dordevic, Milos
AU  - Kaufmann, Jörn
AU  - Avetisyan, Araks
AU  - Skalej, Martin
AU  - Müller, Notger
TI  - Investigation of the functional pathogenesis of mild cognitive impairment by localisation‐based locus coeruleus resting‐state fMRI
JO  - Human brain mapping
VL  - 43
IS  - 18
SN  - 1065-9471
CY  - New York, NY
PB  - Wiley-Liss
M1  - DZNE-2022-01425
SP  - 5630-5642
PY  - 2022
N1  - CC BY-NC-ND: https://creativecommons.org/licenses/by-nc-nd/4.0/
AB  - Dementia as one of the most prevalent diseases urges for a better understanding of the central mechanisms responsible for clinical symptoms, and necessitates improvement of actual diagnostic capabilities. The brainstem nucleus locus coeruleus (LC) is a promising target for early diagnosis because of its early structural alterations and its relationship to the functional disturbances in the patients. In this study, we applied our improved method of localisation-based LC resting-state fMRI to investigate the differences in central sensory signal processing when comparing functional connectivity (fc) of a patient group with mild cognitive impairment (MCI, n = 28) and an age-matched healthy control group (n = 29). MCI and control participants could be differentiated in their Mini-Mental-State-Examination (MMSE) scores (p < .001) and LC intensity ratio (p = .010). In the fMRI, LC fc to anterior cingulate cortex (FDR p < .001) and left anterior insula (FDR p = .012) was elevated, and LC fc to right temporoparietal junction (rTPJ, FDR p = .012) and posterior cingulate cortex (PCC, FDR p = .021) was decreased in the patient group. Importantly, LC to rTPJ connectivity was also positively correlated to MMSE scores in MCI patients (p = .017). Furthermore, we found a hyperactivation of the left-insula salience network in the MCI patients. Our results and our proposed disease model shed new light on the functional pathogenesis of MCI by directing to attentional network disturbances, which could aid new therapeutic strategies and provide a marker for diagnosis and prediction of disease progression.
KW  - Humans
KW  - Locus Coeruleus: diagnostic imaging
KW  - Magnetic Resonance Imaging
KW  - Cognitive Dysfunction: diagnostic imaging
KW  - Gyrus Cinguli
KW  - Brain Stem
KW  - attention (Other)
KW  - locus coeruleus (Other)
KW  - mild cognitive impairment (Other)
KW  - resting-state fMRI (Other)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9704796
C6  - pmid:36441846
DO  - DOI:10.1002/hbm.26039
UR  - https://pub.dzne.de/record/165118
ER  -