Individual Correspondence of Amyloid-β and Intrinsic Connectivity in the Posterior Default Mode Network Across Stages of Alzheimer’s Disease

Background: While amyloid-β (Aβ) plaques and tau tangles are the well-recognized pathologies of Alzheimer’s disease (AD), they are more often observed in healthy individuals than in AD patients. This discrepancy makes it extremely challenging to utilize these two proteinopathies as reliable biomarkers for the early detection as well as later diagnosis of AD. Objective: We hypothesize and provide preliminary evidence that topographically overlapping Aβ and tau within the default mode network (DMN) play more critical roles in the underlying pathophysiology of AD than each of the tau and/or Aβ pathologies alone. Methods: We used our newly developed quantification methods and publicly available neuroimaging data from 303 individuals to provide preliminary evidence of our hypothesis. Results: We first showed that the probability of observing overlapping Aβ and tau is significantly higher within than outside the DMN. We then showed evidence that using Aβ and tau overlap can increase the reliability of the prediction of healthy individuals converting to mild cognitive impairment (MCI) and to a lesser degree converting from MCI to AD. Finally, we provided evidence that while the initial accumulations of Aβ and tau seems to be started independently in the healthy participants, the accumulations of the two pathologies interact in the MCI and AD groups. Conclusion: These findings shed some light on the complex pathophysiology of AD and suggest that overlapping Aβ and tau pathologies within the DMN might be a more reliable biomarker of AD for early detection and later diagnosis of the disease.

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Spectral dynamic causal modelling of resting-state fMRI: an exploratory study relating effective brain connectivity in the default mode network to genetics

Statistical Applications in Genetics and Molecular Biology ◽

10.1515/sagmb-2019-0058 ◽

2020 ◽

Vol 19 (3) ◽

Author(s):

Yunlong Nie ◽

Eugene Opoku ◽

Laila Yasmin ◽

Yin Song ◽

Jie Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Default Mode Network ◽

Resting State ◽

Brain Connectivity ◽

Parametric Bootstrap ◽

Imaging Genetics ◽

Nucleotide Polymorphisms ◽

Mixed Effect ◽

Default Mode

AbstractWe conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer’s disease and mild cognitive impairment. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set which is obtained out-of-sample from 663 ADNI subjects having only genome-wide data. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). In both cases we implement a parametric bootstrap for testing SNP coefficients and make comparisons with p-values obtained from asymptotic null distributions. In both networks at an initial q-value threshold of 0.1 no effects are found. We report on exploratory patterns of associations with relatively high ranks that exhibit stability to the differing assumptions made by both FSR and LME.

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IC-P-133: Music as a probe of default mode network function in young-onset Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2015.06.155 ◽

2015 ◽

Vol 11 (7S_Part_2) ◽

pp. P91-P91

Author(s):

Catherine F. Slattery ◽

Jennifer L. Agustus ◽

Ross W. Paterson ◽

Mark J. White ◽

Alexander J.M. Foulkes ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Default Mode Network ◽

Default Mode ◽

Young Onset ◽

Network Function

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The Effects of Gene Mutations on Default Mode Network in Familial Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-160730 ◽

2017 ◽

Vol 56 (1) ◽

pp. 327-334 ◽

Cited By ~ 5

Author(s):

Xiaozhen Li ◽

Eric Westman ◽

Steinunn Thordardottir ◽

Anne Kinhult Ståhlbom ◽

Ove Almkvist ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Default Mode Network ◽

Gene Mutations ◽

Familial Alzheimer’S Disease ◽

Default Mode ◽

Familial Alzheimer's Disease

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P3-449: THE APOLIPOPROTEIN E GENE AFFECTS THE DEFAULT MODE NETWORK ACROSS THE ALZHEIMER'S DISEASE SPECTRUM

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.1812 ◽

2006 ◽

Vol 14 (7S_Part_24) ◽

pp. P1289-P1290

Author(s):

Yao Zhu ◽

Liang Gong ◽

Ren Qing-Guo ◽

Chunming Xie

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apolipoprotein E ◽

Default Mode Network ◽

Default Mode ◽

E Gene ◽

Disease Spectrum ◽

Apolipoprotein E Gene

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Minimum Spanning Tree Reflects the Alterations of the Default Mode Network During Alzheimer’s Disease

Annals of Biomedical Engineering ◽

10.1007/s10439-011-0258-9 ◽

2011 ◽

Vol 39 (5) ◽

pp. 1493-1504 ◽

Cited By ~ 42

Author(s):

Koray Çiftçi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Default Mode Network ◽

Spanning Tree ◽

Minimum Spanning Tree ◽

Default Mode

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Cognitive Improvement is Correlated with Increased Dynamic Functional Connectivity of Default Mode Network by Personalized rTMS in Alzheimer's Disease

10.21203/rs.3.rs-554187/v1 ◽

2021 ◽

Author(s):

Lili Wei ◽

Jintao Wang ◽

Yingchun Zhang ◽

Luoyi Xu ◽

Kehua Yang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Functional Connectivity ◽

Default Mode Network ◽

Present Report ◽

Verbal Learning ◽

Dynamic Functional Connectivity ◽

Default Mode ◽

Cognitive Improvement ◽

Promising Therapeutic Approach

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) is thought to be a promising therapeutic approach for Alzheimer's disease patients. Methods In the present report, a double-blind, randomized, sham-controlled rTMS trial was conducted in mild-to-moderate Alzheimer's disease patients. High-frequency rTMS was delivered to a subject-specific left lateral parietal region that demonstrated highest functional connectivity with the hippocampus using resting-state fMRI. The Mini Mental State Examination (MMSE) and Philadelphia Verbal Learning Test (PVLT) were used to evaluate patients’ cognitive functions. Results Patients receiving active rTMS treatment (n = 31) showed a significant increase in the MMSE, PVLT-Immediate recall, and PVLT-Short Delay recall scores after two weeks of rTMS treatment, whereas patients who received sham rTMS (n = 27) did not show significant changes in these measures. Dynamic functional connectivity (dFC) magnitude of the default mode network (DMN) in the active-rTMS group showed a significant increase after two weeks of rTMS treatment, and no significant changes were found in the sham-rTMS group. There was a significantly positive correlation between changes of the MMSE and changes of the dFC magnitude of DMN in the active-rTMS group, but not the sham-rTMS group. Conclusions Our findings are novel in demonstrating the feasibility and effectiveness of the fMRI-guided rTMS treatment in Alzheimer's disease patients, and DMN might play a vital role in therapeutic effectiveness of rTMS in Alzheimer’s disease. Trial registration: China National Medical Research Platform (http://114.255.48.20/login, No:MR-33-20-004217), retrospectively registered 2020-12-23.

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