Metabolic connectivity of resting-state networks in alpha synucleinopathies, from prodromal to dementia phase

Abstract

Previous evidence suggests that the derangement of large-scale brain networks reflects structural, molecular, and functional mechanisms underlying neurodegenerative diseases. Although the alterations of multiple large-scale brain networks in Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are reported, a comprehensive study on connectivity reconfiguration starting from the preclinical phase is still lacking. We aimed to investigate shared and disease-specific changes in the large-scale networks across the Lewy Bodies (LB) disorders spectrum using a brain metabolic connectivity approach. We included 30 patients with isolated REM sleep behavior disorder (iRBD), 28 with stable PD, 30 with DLB, and 30 healthy controls for comparison. We applied seed-based interregional correlation analyses (IRCA) to evaluate the metabolic connectivity in the large-scale resting-state networks, as assessed by [18F]FDG-PET, in each clinical group compared to controls. We assessed metabolic connectivity changes by applying the IRCA and specific connectivity metrics, such as the weighted and unweighted Dice similarity coefficients (DC), for the topographical similarities. All the investigated large-scale brain resting-state networks showed metabolic connectivity alterations, supporting the widespread involvement of brain connectivity within the alpha-synuclein spectrum. Connectivity alterations were already evident in iRBD, severely affecting the posterior default mode, attentive and limbic networks. Strong similarities emerged in iRBD and DLB that showed comparable connectivity alterations in most large-scale networks, particularly in the posterior default mode and attentive networks. Contrarily, PD showed the main connectivity alterations limited to motor and somatosensory networks. The present findings reveal that metabolic connectivity alterations in the large-scale networks are already present in the early iRBD phase, resembling the DLB metabolic connectivity changes. This suggests and confirms iRBD as a risk condition for progression to the severe LB disease phenotype. Of note, the neurobiology of stable PD supports its more benign phenotype.

Mapping brain metabolism, connectivity and neurotransmitters topography in early and late onset dementia with lewy bodies

“…Attentional de cits are listed in the consensus clinical criteria for DLB diagnosis and are useful for differential diagnosis with dementia due to AD [33,34]. Connectivity alterations in ATN were previously described in other studies conducted in DLB patients both in the prodromal and dementia phases [35]. Here it appears a functional marker of LO-DLB.…”

Mapping brain metabolism, connectivity and neurotransmitters topography in early and late onset dementia with Lewy bodies

“…Attentional de cits are listed in the consensus clinical criteria for DLB diagnosis and are useful for differential diagnosis with dementia due to AD [33,34]. Connectivity alterations in ATN were previously described in other studies conducted in DLB patients both in the prodromal and dementia phases [35]. Here it appears a functional marker of LO-DLB.…”

The mechanistic effects of acupuncture in rodent neurodegenerative disease models: a literature review

“…As the aggregation and spreading of abnormal proteins are shared pathogenetic mechanisms in the neural degeneration process, similar metabolic connectivity changes have been reported at the brain network level (Boccalini et al, 2022). Well-organized neural circuits via precise complex connectivity between neurons have been recognized as the foundation of specific neural functions.…”