Evaluating resting-state BOLD variability in relation to biomarkers of preclinical Alzheimer's disease

Millar, Peter R.; Ances, Beau M.; Gordon, Brian A.; Benzinger, Tammie L.S.; Morris, John C.; Balota, David A.

doi:10.1016/j.neurobiolaging.2020.08.007

Cited by 24 publications

(23 citation statements)

References 61 publications

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“…We show that abnormalities in cerebral microvascular function, measured using resting state fluctuation amplitudes (RSFA), persist many months after hospitalisation for acute COVID-19. The location of these abnormalities in lateral frontal and temporoparietal regions aligns partly with cerebrovascular dysfunction reported in association with ageing (Tsvetanov et al, 2020b(Tsvetanov et al, , 2015, preclinical Alzheimer's disease (Millar et al, 2020a) and systemic cardiovascular health (Tsvetanov et al, 2020b).These post-COVID-19 effects were observed over and above age. They are related to severity of the acute illness and the host response in the acute stage.…”

Section: Discussionsupporting

confidence: 76%

“…It is easier and safer to apply in clinical cohorts than experimental hypercapnia, breath-holding and drug interventions (Keyeux et al, 1995; Rostrup et al, 1996, 1994; Wagerle and Mishra, 1988). RSFA is sensitive to cerebrovascular and cardiovascular differences in ageing (Garrett et al, 2017; Tsvetanov et al, 2020b, 2015), small vessel disease (Makedonov et al, 2013), stroke (Nair et al, 2017; Raut et al, 2016), Alzheimer’s disease (Makedonov et al, 2016; Millar et al, 2020a), cognitive performance (Liu et al, 2021; Millar et al, 2021, 2020b) and the presence of brain tumours (Agarwal et al, 2019, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study

Tsvetanov

Spindler

Stamatakis

et al. 2022

Preprint

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Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. Here we assess cerebrovascular health in 45 hospitalised patients using the resting state fluctuation amplitudes (RSFA) from functional magnetic resonance imaging, in relation to disease severity and in contrast with 42 controls. Widespread changes in frontoparietal RSFA were related to the severity of the acute COVID-19 episode, as indexed by COVID-19 WHO Progression Scale, inflammatory and coagulatory biomarkers. This relationship was not explained by chronic cardiorespiratory dysfunction, age, or sex. Exploratory analysis suggests that the level of cerebrovascular dysfunction is associated with cognitive, mental, and physical health at follow-up. The principal findings were consistent across univariate and multivariate approaches. The results indicate chronic cerebrovascular impairment following severe acute COVID-19, with the potential for long-term consequences on cognitive function and mental wellbeing.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study

Tsvetanov

Spindler

Stamatakis

et al. 2022

Preprint

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“…Critically, the basal forebrain emerges as one of the first brain regions to show neuropathology in association with early asymptomatic or prodromal phases of neurodegenerative diseases such as AD (Arendt, Brückner, Morawski, Jäger, & Gertz, 2015;Mesulam, Shaw, Mash, & Weintraub, 2004;Nie et al, 2017;Schmitz et al, 2016;Schmitz et al, 2018;Teipel et al, 2014;Yi et al, 2016), PD (Bohnen & Albin, 2011;Zeighami et al, 2015), and LBD (Grothe et al, 2014). Emerging evidence supports the use of resting-state fMRI as an imaging biomarker of neurodegenerative diseases (Cope et al, 2018;Hampton et al, 2020;Hohenfeld, Werner, & Reetz, 2018;Wisch et al, 2020) suggesting that in early, preclinical phases of neurodegenerative diseases, moment-to-moment variability in BOLD signal at rest may be related to the load of neurodegeneration associated neuropathology (Millar et al, 2020), and may signal either abnormalities in neurovascular coupling (Hillman, 2014;Solis, Hascup, & Hascup, 2020) or alterations in functional connectivity specifically associated with the basal forebrain (Chiesa et al, 2019;Wang, Belden, Hanser, Geddes, & Loui, 2020).…”

Section: Introductionmentioning

confidence: 99%

Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD

Olivé

Makris

Densmore

et al. 2021

Human Brain Mapping

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Individuals with posttraumatic stress disorder (PTSD) are at increased risk for the development of various forms of dementia. Nevertheless, the neuropathological link between PTSD and neurodegeneration remains unclear. Degeneration of the human basal forebrain constitutes a pathological hallmark of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. In this seed-based resting-state (rs-)fMRI study identifying as outcome measure the temporal BOLD signal fluctuation magnitude, a seed-to-voxel analyses assessed temporal correlations between the average BOLD signal within a bilateral whole basal forebrain region-of-interest and each whole-brain voxel among individuals with PTSD (n = 65), its dissociative subtype (PTSD+DS) (n = 38) and healthy controls (n = 46). We found that compared both with the PTSD and healthy controls groups, the PTSD+DS group exhibited increased BOLD signal variability within two nuclei of the seed region, specifically in its extended amygdaloid region: the nucleus accumbens and the sublenticular extended amygdala. This finding is provocative, because it mimics staging models of neurodegenerative diseases reporting allocation of neuropathology in early disease stages circumscribed to the basal forebrain. Here, underlying candidate etiopathogenetic mechanisms are neurovascular uncoupling, decreased connectivity in local-and large-scale neural networks, or disrupted mesolimbic dopaminergic circuitry, acting indirectly upon the basal forebrain cholinergic pathways. These abnormalities may underpin reward-related deficits representing a putative link between persistent traumatic memory in PTSD and anterograde memory deficits in neurodegeneration.Observed alterations of the basal forebrain in the dissociative subtype of PTSD point towards the urgent need for further exploration of this region as a potential candidate vulnerability mechanism for neurodegeneration in PTSD.

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“…When the Aβ level became abnormal, the global SC-FC coupling of MCI_Aβ+ patients decreased with the level of Aβ pathology ( Figure 4 B) and showed an increasing group-level trend compared to HC ( Figure 3 ). Previous studies have demonstrated that abnormality in functional connectivity during this phase of AD progression was correlated with the levels of Aβ pathology, but not tau pathology, in preclinical and prodromal AD [ 31 , 32 ]; this association first occurred in the default mode network in preclinical AD, before gradually spreading to other brain networks over the AD continuum [ 33 ]. Apart from the functional brain network, the association between the topology of the structural brain network and the Aβ burden for patients with MCI [ 34 ] along with a diffuse loss of structural connectivity over the course of Aβ accumulation was also observed [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

et al. 2021

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Previous studies have demonstrated that the accumulation of amyloid-β (Aβ) pathologies has distinctive stage-specific effects on the structural and functional brain networks along the Alzheimer’s disease (AD) continuum. A more comprehensive account of both types of brain network may provide a better characterization of the stage-specific effects of Aβ pathologies. A potential candidate for this joint characterization is the coupling between the structural and functional brain networks (SC-FC coupling). We therefore investigated the effect of Aβ accumulation on global SC-FC coupling in patients with mild cognitive impairment (MCI), AD, and healthy controls. Patients with MCI were dichotomized according to their level of Aβ pathology seen in 18F-flutemetamol PET-CT scans—namely, Aβ-negative and Aβ-positive. Our results show that there was no difference in global SC-FC coupling between different cohorts. During the prodromal AD stage, there was a significant negative correlation between the level of Aβ pathology and the global SC-FC coupling of MCI patients with positive Aβ, but no significant correlation for MCI patients with negative Aβ. During the AD dementia stage, the correlation between Aβ pathology and global SC-FC coupling in patients with AD was positive. Our results suggest that Aβ pathology has distinctive stage-specific effects on global coupling between the structural and functional brain networks along the AD continuum.

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Evaluating resting-state BOLD variability in relation to biomarkers of preclinical Alzheimer's disease

Cited by 24 publications

References 61 publications

Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study

Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study

Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD

Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

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