Brain Amyloid Burden and Resting-State Functional Connectivity in Late Middle-Aged Hispanics

Tahmi, Mouna; Rippon, Brady; Palta, Priya; Soto, Luisa M. Solis; Ceballos, Fernando; Pardo, Michelle; Sherwood, Greysi; Hernandez, Gabriela; Arevalo, Rodolfo; He, Hengda; Sedaghat, Amirreza; Arabshahi, Soroush; Teresi, Jeanne A.; Moreno, Herman; Brickman, Adam M.; Razlighi, Qolamreza R.; Luchsinger, José A.

doi:10.3389/fneur.2020.529930

Cited by 8 publications

(4 citation statements)

References 41 publications

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“…We did not detect any significant associations between pathological brain burden and changes in RSFC trajectories within the intrinsic brain networks. This observation replicates the previous study ( Köbe et al, 2021 ) and is in part convergent with other reports ( Tahmi et al, 2020 ). Cross-sectional studies have, however, documented RSFC alterations in the setting of Aβ burden or vascular brain injury in non-clinical and clinical cohorts ( Hedden et al, 2009 ; Mormino et al, 2009 ; Elman et al, 2016 ; Schulz et al, 2021 ), with some of the Aβ-related RSFC alterations involving more focal hub regions ( Hedden et al, 2009 ; Mormino et al, 2011 ).…”

Section: Discussionsupporting

confidence: 94%

Vascular Health Is Associated With Functional Connectivity Decline in Higher-Order Networks of Older Adults

Wirth

Gaubert

Köbe

et al. 2022

Front. Integr. Neurosci.

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BackgroundPoor vascular health may impede brain functioning in older adults, thus possibly increasing the risk of cognitive decline and Alzheimer’s disease (AD). The emerging link between vascular risk factors (VRF) and longitudinal decline in resting-state functional connectivity (RSFC) within functional brain networks needs replication and further research in independent cohorts.MethodWe examined 95 non-demented older adults using the IMAP+ cohort (Caen, France). VRF were assessed at baseline through systolic and diastolic blood pressure, body-mass-index, and glycated hemoglobin (HbA1c) levels. Brain pathological burden was measured using white matter hyperintensity (WMH) volumes, derived from FLAIR images, and cortical β-Amyloid (Aβ) deposition, derived from florbetapir-PET imaging. RSFC was estimated from functional MRI scans within canonical brain networks at baseline and up to 3 years of follow-up. Linear mixed-effects models evaluated the independent predictive value of VRF on longitudinal changes in network-specific and global RSFC as well as a potential association between these RSFC changes and cognitive decline.ResultsWe replicate that RSFC increased over time in global RSFC and in the default-mode, salience/ventral-attention and fronto-parietal networks. In contrast, higher diastolic blood pressure levels were independently associated with a decrease of RSFC over time in the default-mode, salience/ventral-attention, and fronto-parietal networks. Moreover, higher HbA1c levels were independently associated with a reduction of the observed RSFC increase over time in the salience/ventral-attention network. Both of these associations were independent of brain pathology related to Aβ load and WMH volumes. The VRF-related changes in RSFC over time were not significantly associated with longitudinal changes in cognitive performance.ConclusionOur longitudinal findings corroborate that VRF promote RSFC alterations over time within higher-order brain networks, irrespective of pathological brain burden. Altered RSFC in large-scale cognitive networks may eventually increase the vulnerability to aging and AD.

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Section: Discussionsupporting

confidence: 94%

Vascular Health Is Associated With Functional Connectivity Decline in Higher-Order Networks of Older Adults

Wirth

Gaubert

Köbe

et al. 2022

Front. Integr. Neurosci.

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“…Using the voxelwise approach, another study showed both positive and negative associations [40]. Finally, 2 studies reported a nonsignificant correlation between amyloid PET and FC [41, 42].…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of the Association between Amyloid-β and τ Pathology with Functional Connectivity Alterations in the Alzheimer Dementia Spectrum Utilizing PET Scan and rsfMRI

Hasani¹,

Mayeli²,

Salehi³

et al. 2021

Dement Geriatr Cogn Disord Extra

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The association between functional connectivity (FC) alterations with amyloid-β (Aβ) and τ protein depositions in Alzheimer dementia is a subject of debate in the current literature. Although many studies have suggested a declining FC accompanying increased Aβ and τ concentrations, some investigations have contradicted this hypothesis. Therefore, this systematic review was conducted to sum up the current literature in this regard. The PROSPERO guideline for systematic reviews was applied for development of a research protocol, and this study was initiated after getting the protocol approval. Studies were screened, and those investigating FC measured by resting-state functional MRI and Aβ and τ protein depositions using amyloid and τ positron emission tomography were included. We categorized the included studies into 3 groups methodologically, addressing the question using global connectivity analysis (examining all regions of interest across the brain based on a functional atlas), seed-based connectivity analysis, or within-networks connectivity analysis. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Among 31 included studies, 14 found both positive and negative correlations depending on the brain region and stage of the investigated disease, while 7 showed an overall negative correlation, 8 indicated an overall positive correlation, and 2 found a nonsignificant association between protein deposition and FC. The investigated regions were illustrated using tables. The posterior default mode network, one of the first regions of amyloid accumulation, and the temporal lobe, the early τ deposition region, are the 2 most investigated regions where inconsistencies exist. In conclusion, our study indicates that transneuronal spreading of τ and the amyloid hypothesis can justify higher FC related to higher protein depositions when global connectivity analysis is applied. However, the discrepancies observed when investigating the brain locally could be due to the varying manifestations of the amyloid and τ overload compensatory mechanisms in the brain at different stages of the disease with hyper- and hypoconnectivity cycles that can occur repeatedly. Nevertheless, further studies investigating both amyloid and τ deposition simultaneously while considering the stage of Alzheimer dementia are required to assess the accuracy of this hypothesis.

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“…Our rs-fMRI processing pipeline combines steps from the FSL toolbox 35 and in-house-developed techniques 36 . To summarize, slice timing correction was applied to the raw rs-fMRI time series to account for the difference in the acquisition delay between slices.…”

Section: Image Preprocessingmentioning

confidence: 99%

Between-networks hyperconnectivity is induced by beta-amyloid and may facilitate tau spread

Hojjati,

Butler,

Leon

et al. 2024

Preprint

Self Cite

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Alzheimer’s disease (AD) is characterized by the buildup of neurofibrillary tau tangles and beta-amyloid (Aβ) plaques. While it has been hypothesized that Aβ facilitates the spread of tau outside of the medial temporal lobe (MTL), the specific pathological processes and mechanisms by which this occurs remain poorly understood. Our study employed advanced neuroimaging techniques, integrating 18F-Florbetaben Aβ and 18F-MK6240 tau positron emission tomography (PET) with resting-state functional magnetic resonance imaging (rs-fMRI) to characterize these mechanisms in two distinct datasets, that included 481 healthy elderly subjects, 46 of whom came with longitudinal data. Our research highlighted an intricate internetwork relationship between Aβ and tau accumulation, across spatially distinct functional networks. Additionally, we observed compelling evidence supporting the existence of a compensatory mechanism triggered by Aβ accumulation, resulting in hyperconnectivity between functional networks. Finally, the longitudinal findings indicate that between-networks hyperconnectivity is associated with future tau elevation and mediates the relationship between cortical Aβ and early-stage tau. Understanding this early brain alteration in response to the accumulation of Aβ could guide treatments early in the disease course and potentially prevent future tau accumulation.

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Brain Amyloid Burden and Resting-State Functional Connectivity in Late Middle-Aged Hispanics

Cited by 8 publications

References 41 publications

Vascular Health Is Associated With Functional Connectivity Decline in Higher-Order Networks of Older Adults

Vascular Health Is Associated With Functional Connectivity Decline in Higher-Order Networks of Older Adults

A Systematic Review of the Association between Amyloid-β and τ Pathology with Functional Connectivity Alterations in the Alzheimer Dementia Spectrum Utilizing PET Scan and rsfMRI

Between-networks hyperconnectivity is induced by beta-amyloid and may facilitate tau spread

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