TY - JOUR
T1 - Brain metabolic correlates of Locus Coeruleus degeneration in Alzheimer's disease
T2 - a multimodal neuroimaging study
AU - Aghakhanyan, Gayane
AU - Galgani, Alessandro
AU - Vergallo, Andrea
AU - Lombardo, Francesco
AU - Martini, Nicola
AU - Baldacci, Filippo
AU - Tognoni, Gloria
AU - Leo, Andrea
AU - Guidoccio, Federica
AU - Siciliano, Gabriele
AU - Fornai, Francesco
AU - Pavese, Nicola
AU - Volterrani, Duccio
AU - Giorgi, Filippo S.
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2023/2
Y1 - 2023/2
N2 - Locus Coeruleus (LC) degeneration occurs early in Alzheimer's disease (AD) and this could affect several brain regions innervated by LC noradrenergic axon terminals, as these bear neuroprotective effects and modulate neurovascular coupling/neuronal activity. We used LC-sensitive Magnetic Resonance imaging (MRI) sequences enabling LC integrity quantification, and [18F]Fluorodeoxyglucose (FDG) PET, to investigate the association of LC-MRI changes with brain glucose metabolism in cognitively impaired patients (30 amnesticMCI and 13 demented ones). Fifteen cognitively intact age-matched controls (HCs) were submitted only to LC-MRI for comparison with patients. Voxel-wise regression analyses of [18F]FDG images were conducted using the LC-MRI parameters signal intensity (LCCR) and LC-belonging voxels (LCVOX). Both LCCR and LCVOX were significantly lower in patients compared to HCs, and were directly associated with [18F]FDG uptake in fronto-parietal cortical areas, mainly involving the left hemisphere (p < 0.001, kE > 100). These results suggest a possible association between LC degeneration and cortical hypometabolism in degenerative cognitive impairment with a prevalent left-hemispheric vulnerability, and that LC degeneration might be linked to large-scale functional network alteration in AD pathology.
AB - Locus Coeruleus (LC) degeneration occurs early in Alzheimer's disease (AD) and this could affect several brain regions innervated by LC noradrenergic axon terminals, as these bear neuroprotective effects and modulate neurovascular coupling/neuronal activity. We used LC-sensitive Magnetic Resonance imaging (MRI) sequences enabling LC integrity quantification, and [18F]Fluorodeoxyglucose (FDG) PET, to investigate the association of LC-MRI changes with brain glucose metabolism in cognitively impaired patients (30 amnesticMCI and 13 demented ones). Fifteen cognitively intact age-matched controls (HCs) were submitted only to LC-MRI for comparison with patients. Voxel-wise regression analyses of [18F]FDG images were conducted using the LC-MRI parameters signal intensity (LCCR) and LC-belonging voxels (LCVOX). Both LCCR and LCVOX were significantly lower in patients compared to HCs, and were directly associated with [18F]FDG uptake in fronto-parietal cortical areas, mainly involving the left hemisphere (p < 0.001, kE > 100). These results suggest a possible association between LC degeneration and cortical hypometabolism in degenerative cognitive impairment with a prevalent left-hemispheric vulnerability, and that LC degeneration might be linked to large-scale functional network alteration in AD pathology.
KW - Alzheimer's disease
KW - Locus Coeruleus
KW - Locus Coeruleus Integrity
KW - Magnetic Resonance imaging
KW - [18F]Fluorodeoxyglucose Positron Emission Tomography
KW - Neuroimaging
KW - Locus Coeruleus/pathology
KW - Humans
KW - Magnetic Resonance Imaging/methods
KW - Fluorodeoxyglucose F18/metabolism
KW - Alzheimer Disease/metabolism
KW - Positron-Emission Tomography/methods
KW - Brain/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85143507753&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2022.11.002
DO - 10.1016/j.neurobiolaging.2022.11.002
M3 - Journal article
C2 - 36463849
AN - SCOPUS:85143507753
SN - 0197-4580
VL - 122
SP - 12
EP - 21
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -