Connectivity between default mode and frontoparietal networks mediates the association between global amyloid‐β and episodic memory

Zhukovsky, Peter; Coughlan, Gillian; Buckley, Rachel F.; Grady, Cl; Voineskos, Aristotle N.

doi:10.1002/hbm.26148

Cited by 5 publications

(3 citation statements)

References 74 publications

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“…By employing comprehensive machine learning methods, we have demonstrated that between networks functional fronto-parietal connectivity is a strong mediator of the effect of cognitive reserve on cognitive outcomes in ageing population. Our findings provide additional support for Robertson’s theory of cognitive reserve (Robertson, 2013, 2014), and recent finding in Alzheimer’s patients linking between networks frontoparietal connectivity to offsetting effects of cognitive reserve against amyloid burden (Zhukovsky et al, 2023). While on one hand the limitation of the current study is that we only examined between network connections, on the other hand several theories of cognitive ageing explicitly address changes in functional correlations between functional networks associated with either preservation or decline in cognitive performance in ageing.…”

Section: Discussionsupporting

confidence: 87%

“…In addition, when examining a small sample of Alzheimer's patients, Bozzali and colleagues (2015) previously found evidence that cognitive reserve modulate connectivity within the default mode network. Finally, our results expand on newly published findings linking changes in connectivity between the default mode network and frontoparietal networks to cognitive decline in elderly (Koshino et al, 2023) and to the effects of beta-amyloid on cognitive status in Alzheimer's patients (Zhukovsky et al, 2023).…”

Section: Discussionsupporting

confidence: 84%

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Modelling cognitive outcomes in the UK Biobank: education, noradrenaline and frontoparietal networks

Bravo-Merodio,

Williams,

Russ

et al. 2023

Preprint

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Cognitive reserve measured by proxies of life experiences is thought to account for the heterogeneity in cognitive ageing. One hypothesis is that cognitively enriched environments acting on the noradrenergic system strengthen the right fronto-parietal networks to facilitate cognitive reserve and maintain cognition throughout the lifetime. We used machine learning and mediation analysis to model interactions between neurobiological features (genetic variants in noradrenergic signalling, structural and functional fronto-parietal connectivity measures) and cognitive reserve (by proxy of education) on cognitive outcomes (general cognitive ability score) in the ageing UK Biobank cohort. We show that: (1) interactions between education and neurobiological variables more fully explain general cognitive ability than either factor alone; (2) among the examined neurobiological features, measures of fronto-parietal connectivity are the strongest mediators of the effect of education on cognitive outcomes. In particular, our findings point to two between-networks connectivity measures representing, connections linking the default mode network with the right fronto-parietal network, and with the executive control network as the key mediators between cognitively enriched environments and cognitive outcomes.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 84%

Modelling cognitive outcomes in the UK Biobank: education, noradrenaline and frontoparietal networks

Bravo-Merodio,

Williams,

Russ

et al. 2023

Preprint

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“…In both memory types, key networks are situated in the medial and lateral temporal lobes 7,8,9,10,11,12,[13][14][15][16]17,18 , alongside posterior parietal regions [19][20][21] . More broadly, networks involved in both memory types have been shown to engage similar intrinsic functional systems, notably the fronto-parietal network [22][23][24] (FPN) and the default mode network 10,25,26 (DMN). As such, consistent behavioral and neural evidence suggests shared processes implicated in both forms of declarative memory.…”

Section: Introductionmentioning

confidence: 99%

Differential Reorganization of Episodic and Semantic Memory Systems in Epilepsy-Related Mesiotemporal Pathology

Cabalo,

DeKraker,

Royer

et al. 2023

Preprint

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Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, while semantic memory houses context-independent knowledge. Behavioral and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions and distributed neocortices. Here, we studied a population of patients with unilateral temporal lobe epilepsy (TLE) and variable degrees of MTL pathology as a human disease model to explore declarative memory system reorganization, and to examine neurocognitive associations. Our cohort included 20 patients with TLE as well as 60 age and sex-matched healthy controls, who underwent episodic and semantic retrieval tasks during a functional MRI session. Tasks were closely matched in terms of stimuli and trial design. Capitalizing on connectome gradient mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, both in the MTL and in neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed topographic reorganization during episodic but not semantic memory states, characterized by marked gradient compression in lateral temporal and midline parietal cortices in both hemispheres, cooccurring with an expansion of anterior-posterior hippocampal differentiation ipsilateral to the MTL pathology. These findings suggest that episodic processes are supported by a distributed network, implicating both hippocampus and neocortex, and such alterations can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage such as TLE. Leveraging microstructural and morphological MRI proxies of MTL pathology, we furthermore observed that pathological markers selective to the hippocampus are associated with TLE-related functional reorganization. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioral deficits in episodic memory in patients. Altogether, our findings point to a selective mesiotemporal and neocortical functional reorganization of episodic memory systems in patients with TLE, which consistently affects behavioral memory deficits. These findings point to consistent structure-function relationships in declarative memory and reaffirm the critical role of the MTL in episodic memory systems.

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Connectivity between default mode and frontoparietal networks mediates the association between global amyloid‐β and episodic memory

Zhukovsky

Coughlan

Buckley

et al. 2022

Human Brain Mapping

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Βeta‐amyloid (Aβ) is a neurotoxic protein that deposits early in the pathogenesis of preclinical Alzheimer's disease. We aimed to identify network connectivity that may alter the negative effect of Aβ on cognition. Following assessment of memory performance, resting‐state fMRI, and mean cortical PET‐Aβ, a total of 364 older adults (286 with clinical dementia rating [CDR‐0], 59 with CDR‐0.5 and 19 with CDR‐1, mean age: 74.0 ± 6.4 years) from the OASIS‐3 sample were included in the analysis. Across all participants, a partial least squares regression showed that lower connectivity between posterior medial default mode and frontoparietal networks, higher within‐default mode, and higher visual–motor connectivity predict better episodic memory. These connectivities partially mediate the effect of Aβ on episodic memory. These results suggest that connectivity strength between the precuneus cortex and the superior frontal gyri may alter the negative effect of Aβ on episodic memory. In contrast, education was associated with different functional connectivity patterns. In conclusion, functional characteristics of specific brain networks may help identify amyloid‐positive individuals with a higher likelihood of memory decline, with implications for AD clinical trials.

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Connectivity between default mode and frontoparietal networks mediates the association between global amyloid‐β and episodic memory

Cited by 5 publications

References 74 publications

Modelling cognitive outcomes in the UK Biobank: education, noradrenaline and frontoparietal networks

Modelling cognitive outcomes in the UK Biobank: education, noradrenaline and frontoparietal networks

Differential Reorganization of Episodic and Semantic Memory Systems in Epilepsy-Related Mesiotemporal Pathology

Connectivity between default mode and frontoparietal networks mediates the association between global amyloid‐β and episodic memory

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