Sex differences in brain metabolic connectivity architecture in probable dementia with Lewy bodies

Silvia Paola Caminiti; Cecilia Boccalini; Nicolas Nicastro; Valentina Garibotto; Daniela Perani; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.neurobiolaging.2023.02.004

Sex differences in brain metabolic connectivity architecture in probable dementia with Lewy bodies

Neurobiol Aging. 2023 Jun:126:14-24. doi: 10.1016/j.neurobiolaging.2023.02.004. Epub 2023 Feb 17.

Authors

Silvia Paola Caminiti¹, Cecilia Boccalini², Nicolas Nicastro³, Valentina Garibotto⁴, Daniela Perani⁵; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ School of Psychology, Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
² School of Psychology, Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
³ Division of Neurorehabilitation, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland.
⁴ Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland; Center for Biomedical Imaging (CIBM), Geneva, Switzerland.
⁵ School of Psychology, Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: perani.daniela@hsr.it.

PMID: 36905876
DOI: 10.1016/j.neurobiolaging.2023.02.004

Abstract

We investigated how sex modulates metabolic connectivity alterations in probable dementia with Lewy bodies (pDLB). We included 131 pDLB patients (males/females: 58/73) and similarly aged healthy controls (HC) (male/female: 59/75) with available (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans. We assessed (1) sex differences in the whole-brain connectivity, identifying pathological hubs, (2) connectivity alterations in functional pathways of the neurotransmitter systems, (3) Resting State Networks (RSNs) integrity. Both pDLB_M (males) and pDLB_F (females) shared dysfunctional hubs in the insula, Rolandic operculum, and inferior parietal lobule, but the pDLB_M group showed more severe and diffuse whole-brain connectivity alterations. Neurotransmitters connectivity analysis revealed common alterations in dopaminergic and noradrenergic pathways. Sex differences emerged particularly in the Ch4-perisylvian division, with pDLB_M showing more severe alterations than pDLB_F. The RSNs analysis showed no sex differences, with decreased connectivity strength in the primary visual, posterior default mode, and attention networks in both groups. Extensive connectivity changes characterize both males and females in the dementia stage, with a major vulnerability of cholinergic neurotransmitter systems in males, possibly contributing to the observed different clinical phenotypes.

Keywords: Alpha-synuclein; Brain Hypometabolism; Neurodegeneration; Sex; Vulnerability.

MeSH terms

Brain / metabolism
Brain Mapping
Female
Humans
Insular Cortex
Lewy Body Disease* / metabolism
Magnetic Resonance Imaging
Male
Positron-Emission Tomography