Differential default-mode network effective connectivity in young-onset Alzheimer’s disease variants

Abstract Young-onset Alzheimer’s Disease is a rare form of Alzheimer’s Disease characterized by early symptom onset (< 65 years) and heterogeneous clinical phenotypes. Previous studies have consistently shown that patients with late-onset Alzheimer’s exhibit alterations in the default-mode network—a large-scale brain network associated with self-related processing and autobiographical memory. However, the functional organization of the default-mode network is far less clear in young-onset Alzheimer’s disease. Here, we assessed default-mode network effective connectivity in two common young-onset Alzheimer’s disease variants (i.e., typical amnestic variant and posterior cortical atrophy) and healthy participants to identify disease- and variant-specific differences in the default-mode network.This case-control study was conducted with thirty-nine young-onset Alzheimer’s disease patients, including typical amnestic (n = 26, 15 females, mean age = 61) and posterior cortical atrophy (n = 13; 8 females, mean age = 61.8), and 24 age-matched healthy participants (13 females, mean age=60.1). All participants underwent resting-state functional MRI and extensive neuropsychological testing. Spectral dynamic causal modelling was performed to quantify resting-state effective connectivity between default-mode network regions. Parametric empirical Bayes analysis was then performed to characterise group differences in effective connectivity.Our results showed that patients with typical Alzheimer’s disease variant showed increased connectivity from medial prefrontal cortex to posterior default-mode network nodes as well as reduced inhibitory connectivity from hippocampus to other default-mode network nodes, relative to healthy controls. Patients with posterior cortical atrophy exhibited decreased connectivity from posterior cingulate cortex to medial prefrontal cortex and bilateral angular gyrus and reduced inhibitory connectivity from left hippocampus to other default-mode network nodes compared to healthy controls. Right hippocampus connectivity differentiated the two patient groups. Patients with typical Alzheimer’s disease variant had lower inhibitory connectivity from right hippocampus to other default-mode network nodes than the patients with posterior cortical atrophy.Our findings suggest that resting-state default-mode network connectivity is a physiological phenotype of young-onset Alzheimer’s disease that could contribute to a new understanding of functional integration in this condition..

Medienart:	Preprint

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	bioRxiv.org - (2024) vom: 19. März Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Beteiligte Personen:	Sacu, Seda [VerfasserIn] Slattery, Catherine F. [VerfasserIn] Friston, Karl J. [VerfasserIn] Paterson, Ross W. [VerfasserIn] Foulkes, Alexander J.M. [VerfasserIn] Yong, Keir [VerfasserIn] Crutch, Sebastian [VerfasserIn] Schott, Jonathan M. [VerfasserIn] Razi, Adeel [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	570 Biology

doi:	10.1101/2024.03.11.24304042

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PPN (Katalog-ID):	XBI042924057