Resting-state functional MRI signal fluctuation amplitudes are correlated with brain amyloid-β deposition in patients with mild cognitive impairment

2021 ◽  
pp. 0271678X2110648
Author(s):  
Norman Scheel ◽  
Takashi Tarumi ◽  
Tsubasa Tomoto ◽  
C Munro Cullum ◽  
Rong Zhang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Mri ◽  
Neuronal Activity ◽  
Resting State ◽  
Low Frequency ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Blood Oxygen Level Dependent ◽  
Cerebral White Matter

Mounting evidence suggests that amyloid-β (Aβ) and vascular etiologies are intertwined in the pathogenesis of Alzheimer’s disease (AD). Blood-oxygen-level-dependent (BOLD) signals, measured by resting-state functional MRI (rs-fMRI), are associated with neuronal activity and cerebrovascular hemodynamics. Nevertheless, it is unclear if BOLD fluctuations are associated with Aβ deposition in individuals at high risk of AD. Thirty-three patients with amnestic mild cognitive impairment underwent rs-fMRI and AV45 PET. The AV45 standardized uptake value ratio (AV45-SUVR) was calculated using cerebral white matter as reference, to assess Aβ deposition. The whole-brain normalized amplitudes of low-frequency fluctuations (sALFF) of local BOLD signals were calculated in the frequency band of 0.01–0.08 Hz. Stepwise increasing physiological/vascular signal regressions on the rs-fMRI data examined whether sALFF-AV45 correlations were driven by vascular hemodynamics, neuronal activities, or both. We found that sALFF and AV45-SUVR were negatively correlated in regions of default-mode and visual networks (precuneus, angular, lingual and fusiform gyri). Regions with higher sALFF had less Aβ accumulation. Correlated cluster sizes in MNI space ( r ≈ −0.47) were reduced from 3018 mm3 to 1072 mm3 with stronger cardiovascular regression. These preliminary findings imply that local brain blood fluctuations due to vascular hemodynamics or neuronal activity can affect Aβ homeostasis.

scholarly journals Resting-state functional MRI signal fluctuations are correlated with brain amyloid-β deposition

2021 ◽  
Author(s):  
Norman Scheel ◽  
Takashi Tarumi ◽  
Tsubasa Tomoto ◽  
Munro Cullum ◽  
Rong Zhang ◽  
...  
Keyword(s):  
Functional Mri ◽  
Resting State ◽  
Low Frequency ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Blood Oxygen Level Dependent ◽  
Brain Regions ◽  
Blood Oxygen Level ◽  
Positron Emission ◽  
Local Correlations

Mounting evidence suggests that amyloid-β (Aβ) and vascular etiologies are intertwined in the pathogenesis of Alzheimer′s disease. Spontaneous fluctuations of the brain blood-oxygen-level-dependent (BOLD) signal, as measured by resting-state functional MRI (rs-fMRI), have been shown to be associated with neuronal activities as well as cerebrovascular hemodynamics. Nevertheless, it is unclear if rs-fMRI BOLD fluctuations are associated with brain Aβ deposition in individuals with an elevated risk of Alzheimer's disease. We recruited 33 patients with amnestic mild cognitive impairment who underwent rs-fMRI and positron emission tomography (PET). The Aβ standardized uptake value ratio (SUVR) was calculated with cortical white matter as the reference region to improve sensitivity for cortical Aβ quantification. We calculated the amplitudes of low-frequency fluctuations (ALFF) of local BOLD signals in the frequency band of 0.01-0.08 Hz. Applying physiological/vascular signal regression in stepwise increasing levels on the rs-fMRI data, we examined whether local correlations between ALFF and brain Aβ deposition were driven by vascular hemodynamics, spontaneous neuronal activities, or both. We found that ALFF and Aβ SUVR were negatively correlated in brain regions involving the default-mode and visual networks, with peak correlation at the precuneus, and angular, lingual, and fusiform gyri. Regions with higher ALFF had less Aβ accumulation. The correlated cluster sizes in MNI space were reduced from 3018 mm3 with no physiological/vascular regression to 1072 mm3 with strong physiological/vascular regression, with mean cluster r values at approximately -0.47. Results demonstrate that both vascular hemodynamics and neuronal activities, as reflected by BOLD fluctuations, are negatively associated with brain Aβ deposition. These findings further imply that local brain blood fluctuations due to either vascular hemodynamics or neuronal activities can affect Aβ homeostasis.

scholarly journals Effects of APOE ε2 on the Fractional Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment: A Study Based on the Resting-State Functional MRI

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiaocao Liu ◽  
Qingze Zeng ◽  
Xiao Luo ◽  
Kaicheng Li ◽  
Hui Hong ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Mri ◽  
Resting State ◽  
Fdg Pet ◽  
Brain Activity ◽  
Low Frequency ◽  
Disease Status ◽  
Frequency Fluctuation ◽  
Post Hoc

BackgroundApolipoprotein E (APOE) ε2 is a protective genetic factor for Alzheimer’s disease (AD). However, the potential interaction effects between the APOE ε2 allele and disease status on the intrinsic brain activity remain elusive.MethodsWe identified 73 healthy control (HC) with APOE ε3/ε3, 61 mild cognitive impairment (MCI) subjects with APOE ε3/ε3, 24 HC with APOE ε2/ε3, and 10 MCI subjects with APOE ε2/ε3 from the ADNI database. All subjects underwent a resting-state functional MRI and Fluoro-deoxy-glucose positron emission tomography (FDG-PET). We used a fractional amplitude of low-frequency fluctuation (fALFF) to explore the spontaneous brain activity. Based on the mixed-effects analysis, we explored the interaction effects between the APOE ε2 allele versus disease status on brain activity and metabolism in a voxel-wise fashion (GRF corrected, p < 0.01), followed by post hoc two-sample t-tests (Bonferroni corrected, p < 0.05). We then investigated the relationship between the mean imaging metrics and cognitive abilities.ResultsThere are no significant differences in gender, age, or education among the four groups. The interaction effect on brain activity was located in the inferior parietal lobule (IPL). Post hoc analysis showed that APOE ε2/ε3 MCI had an increased IPL fALFF than APOE ε3/ε3 MCI. Regarding the APOE ε2 allele effects, we found that ε2 carriers had a decreased fALFF in the transverse temporal gyrus than non-carriers. Also, FDG-PET results showed a lower SUVR of the frontal lobe in APOE ε2 carriers than non-carriers. Furthermore, fALFF of IPL was correlated with the visuospatial function (r = −0.16, p < 0.05).ConclusionAPOE ε2 carriers might have a better brain reservation when coping with AD-related pathologies.

scholarly journals Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer’s Disease and Other Dementias

2020 ◽  
pp. 1-14
Author(s):  
Yi-Wen Bao ◽  
Anson C.M. Chau ◽  
Patrick Ka-Chun Chiu ◽  
Yat Fung Shea ◽  
Joseph S.K. Kwan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Subjective Cognitive Decline ◽  
Cognitively Impaired ◽  
Memory Clinic ◽  
Pet Ct

Background: With the more widespread use of 18F-radioligand-based amyloid-β (Aβ) PET-CT imaging, we evaluated Aβ binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. Objective: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer’s disease (AD), and 2) MCI from other non-AD dementias (OD). Methods: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). Results: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aβ binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. Conclusion: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.

scholarly journals 18F-MK-6240 PET for early and late detection of neurofibrillary tangles

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2818-2830 ◽  
Author(s):  
Tharick A Pascoal ◽  
Joseph Therriault ◽  
Andrea L Benedet ◽  
Melissa Savard ◽  
Firoza Z Lussier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Braak Staging ◽  
High Affinity ◽  
Tau Pet ◽  
Transentorhinal Cortex

Abstract Braak stages of tau neurofibrillary tangle accumulation have been incorporated in the criteria for the neuropathological diagnosis of Alzheimer’s disease. It is expected that Braak staging using brain imaging can stratify living individuals according to their individual patterns of tau deposition, which may prove crucial for clinical trials and practice. However, previous studies using the first-generation tau PET agents have shown a low sensitivity to detect tau pathology in areas corresponding to early Braak histopathological stages (∼20% of cognitively unimpaired elderly with tau deposition in regions corresponding to Braak I–II), in contrast to ∼80–90% reported in post-mortem cohorts. Here, we tested whether the novel high affinity tau tangles tracer 18F-MK-6240 can better identify individuals in the early stages of tau accumulation. To this end, we studied 301 individuals (30 cognitively unimpaired young, 138 cognitively unimpaired elderly, 67 with mild cognitive impairment, 54 with Alzheimer’s disease dementia, and 12 with frontotemporal dementia) with amyloid-β 18F-NAV4694, tau 18F-MK-6240, MRI, and clinical assessments. 18F-MK-6240 standardized uptake value ratio images were acquired at 90–110 min after the tracer injection. 18F-MK-6240 discriminated Alzheimer’s disease dementia from mild cognitive impairment and frontotemporal dementia with high accuracy (∼85–100%). 18F-MK-6240 recapitulated topographical patterns consistent with the six hierarchical stages proposed by Braak in 98% of our population. Cognition and amyloid-β status explained most of the Braak stages variance (P < 0.0001, R2 = 0.75). No single region of interest standardized uptake value ratio accurately segregated individuals into the six topographic Braak stages. Sixty-eight per cent of the cognitively unimpaired elderly amyloid-β-positive and 37% of the cognitively unimpaired elderly amyloid-β-negative subjects displayed tau deposition, at least in the transentorhinal cortex (Braak I). Tau deposition solely in the transentorhinal cortex was associated with an elevated prevalence of amyloid-β, neurodegeneration, and cognitive impairment (P < 0.0001). 18F-MK-6240 deposition in regions corresponding to Braak IV–VI was associated with the highest prevalence of neurodegeneration, whereas in Braak V–VI regions with the highest prevalence of cognitive impairment. Our results suggest that the hierarchical six-stage Braak model using 18F-MK-6240 imaging provides an index of early and late tau accumulation as well as disease stage in preclinical and symptomatic individuals. Tau PET Braak staging using high affinity tracers has the potential to be incorporated in the diagnosis of living patients with Alzheimer’s disease in the near future.

scholarly journals Effects of Smoking on Regional Homogeneity in Mild Cognitive Impairment: A Resting-State Functional MRI Study

2020 ◽  
Vol 12 ◽  
Author(s):  
Tianyi Zhang ◽  
Xiao Luo ◽  
Qingze Zeng ◽  
Yanv Fu ◽  
Zheyu Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Mri ◽  
Resting State ◽  
Brain Activity ◽  
Verbal Learning ◽  
Regional Homogeneity ◽  
Angular Gyrus ◽  
Healthy Elderly ◽  
Intrinsic Brain Activity

BackgroundSmoking is a modifiable risk factor for Alzheimer’s disease (AD). However, smoking-related effects on intrinsic brain activity in high-risk AD population are still unclear.ObjectiveWe aimed to explore differences in smoking effects on brain function between healthy elderly and amnestic mild cognitive impairment (aMCI) patients using ReHo mapping.MethodsWe identified 64 healthy elderly controls and 116 aMCI patients, including 98 non-smoking and 18 smoking aMCI. Each subject underwent structural and resting-state functional MRI scanning and neuropsychological evaluations. Regional homogeneity (ReHo) mapping was used to assess regional brain synchronization. After correction for age, gender, education, and gray matter volume, we explored the difference of ReHo among groups in a voxel-wise way based on analysis of covariance (ANCOVA), followed by post hoc two-sample analyses (p < 0.05, corrected). Further, we correlated the mean ReHo with neuropsychological scales.ResultsThree groups were well-matched in age, gender, and education. Significant ReHo differences were found among three groups, located in the left supramarginal gyrus (SMG) and left angular gyrus (AG). Specifically, non-smoking aMCI had lower ReHo in SMG and AG than smoking aMCI and controls. By contrast, smoking aMCI had greater AG ReHo than healthy controls (p < 0.05). Across groups, correlation analyses showed that left AG ReHo correlated with MMSE (r = 0.18, p = 0.015), clock drawing test (r = 0.20, p = 0.007), immediate recall (r = 0.36, p < 0.001), delayed recall (r = 0.34, p < 0.001), and auditory verbal learning test (r = 0.20, p = 0.007).ConclusionSmoking might pose compensatory or protective effects on intrinsic brain activity in aMCI patients.

Sign in / Sign up

Export Citation Format

Share Document