scholarly journals The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer’s disease

2019 ◽  
Author(s):  
Wasim Khan ◽  
Ali Amad ◽  
Vincent Giampietro ◽  
Emilio Werden ◽  
Sara De Simoni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Disease Progression ◽  
Large Scale ◽  
Posterior Cingulate Cortex ◽  
Subjective Memory ◽  
Functional Architecture ◽  
Human Connectome Project ◽  
Data Driven Approach

AbstractThe posteromedial cortex (PMC) is a key region involved in the development and progression of Alzheimer’s disease (AD). Previous studies have demonstrated a heterogenous functional architecture of the region, with different subdivisions reflecting distinct connectivity profiles. However, little is understood about PMC functional connectivity and its differential vulnerability to AD pathogenesis. Using a data-driven approach, we applied a constrained independent component analysis (ICA) on healthy adults from the Human Connectome Project (HCP) to characterise the distinct functional subdivisions and unique functional-anatomic connectivity patterns of the PMC. These connectivity profiles were subsequently quantified in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study, to examine functional connectivity differences in (1) AD patients and cognitively normal (CN) participants and (2) the entire AD pathological spectrum, ranging from CN participants and participants with subjective memory complaints (SMC), through to those with mild cognitive impairment (MCI), and finally, patients diagnosed with AD. Our findings revealed decreased functional connectivity in the anterior precuneus, dorsal posterior cingulate cortex, and the central precuneus in AD patients compared to CN participants. Functional abnormalities in these subdivisions were also related to high amyloid burden and lower hippocampal volumes. Across the entire AD spectrum, functional connectivity of the central precuneus was associated with disease progression and specific deficits in memory and executive function. These findings provide new evidence showing that specific vulnerabilities in PMC functional connectivity are associated with large-scale network disruptions in AD and that these patterns may be useful for elucidating potential biomarkers for measuring disease progression in future work.

scholarly journals Posterior Cingulate Cortex Network Predicts Alzheimer's Disease Progression

2020 ◽  
Vol 12 ◽  
Author(s):  
Pei-Lin Lee ◽  
Kun-Hsien Chou ◽  
Chih-Ping Chung ◽  
Tzu-Hsien Lai ◽  
Juan Helen Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Large Scale ◽  
Cingulate Cortex ◽  
Posterior Cingulate Cortex ◽  
Cognitive Domains ◽  
Atrophy Rate ◽  
Posterior Cingulate ◽  
Structural Networks

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of toxic misfolded proteins, which are believed to have propagated from disease-specific epicenters through their corresponding large-scale structural networks in the brain. Although previous cross-sectional studies have identified potential AD-associated epicenters and corresponding brain networks, it is unclear whether these networks are associated with disease progression. Hence, this study aims to identify the most vulnerable epicenters and corresponding large-scale structural networks involved in the early stages of AD and to evaluate its associations with multiple cognitive domains using longitudinal study design. Annual neuropsychological and MRI assessments were obtained from 23 patients with AD, 37 patients with amnestic mild cognitive impairment (MCI), and 33 healthy controls (HC) for 3 years. Candidate epicenters were identified as regions with faster decline rate in the gray matter volume (GMV) in patients with MCI who progressed to AD as compared to those regions in patients without progression. These epicenters were then further used as pre-defined regions of interest to map the synchronized degeneration network (SDN) in HCs. Spatial similarity, network preference and clinical association analyses were used to evaluate the specific roles of the identified SDNs. Our results demonstrated that the hippocampus and posterior cingulate cortex (PCC) were the most vulnerable AD-associated epicenters. The corresponding PCC-SDN showed significant spatial association with the patterns of GMV atrophy rate in each patient group and the overlap of these patterns was more evident in the advanced stages of the disease. Furthermore, individuals with a higher GMV atrophy rate of the PCC-SDN also showed faster decline in multiple cognitive domains. In conclusion, our findings suggest the PCC and hippocampus are two vulnerable regions involved early in AD pathophysiology. However, the PCC-SDN, but not hippocampus-SDN, was more closely associated with AD progression. These results may provide insight into the pathophysiology of AD from large-scale network perspective.

scholarly journals Differentiating amyloid beta spread in autosomal dominant and sporadic Alzheimer's disease

2021 ◽  
Author(s):  
Elizabeth Levitis ◽  
Jacob W Vogel ◽  
Thomas Funck ◽  
Vladimir Halchinski ◽  
Serge Gauthier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Pattern ◽  
Amyloid Beta ◽  
Large Scale ◽  
Autosomal Dominant ◽  
Model Performance ◽  
Sporadic Alzheimer’S Disease ◽  
Individual Level ◽  
Data Driven Approach

Amyloid-beta (Aβ) deposition is one of the hallmark pathologies in both sporadic Alzheimer's disease (sAD) and autosomal dominant Alzheimer's disease (ADAD), the latter of which is caused by mutations in genes involved in Aβ processing. Despite Aβ deposition being a centerpiece to both sAD and ADAD, some differences between these AD subtypes have been observed with respect to the spatial pattern of Aβ. Previous work has shown that the spatial pattern of Aβ in individuals spanning the sAD spectrum can be reproduced with high accuracy using an epidemic spreading model (ESM), which simulates the diffusion of Aβ across neuronal connections and is constrained by individual rates of Aβ production and clearance. However, it has not been investigated whether Aβ deposition in the rarer ADAD can be modeled in the same way, and if so, how congruent the spreading patterns of Aβ across sAD and ADAD are. We leverage the ESM as a data-driven approach to probe individual-level variation in the spreading patterns of Aβ across three different large-scale imaging datasets (2 SAD, 1 ADAD). We applied the ESM separately to the Alzheimer's Disease Neuroimaging initiative (N=737), the Open Access Series of Imaging Studies (N=510), and the Dominantly Inherited Alzheimer's Network (N=249), the latter two of which were processed using an identical pipeline. We assessed inter- and intra-individual model performance in each dataset separately, and further identified the most likely epicenter of Aβ spread for each individual. Using epicenters defined in previous work in sAD, the ESM provided moderate prediction of the regional pattern of Aβ deposition across all three datasets. We further find that, while the most likely epicenter for most Aβ-positive subjects overlaps with the default mode network, 13% of ADAD individuals were best characterized by a striatal origin of Aβ spread. These subjects were also distinguished by being younger than ADAD subjects with a DMN Aβ origin, despite having a similar estimated age of symptom onset. Together, our results suggest that most ADAD patients express Aβ spreading patters similar to those of sAD, but that there may be a subset of ADAD patients with a separate, striatal phenotype.

scholarly journals The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease

2020 ◽  
Vol 41 (6) ◽  
pp. 1557-1572
Author(s):  
Wasim Khan ◽  
Ali Amad ◽  
Vincent Giampietro ◽  
Emilio Werden ◽  
Sara De Simoni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Functional Architecture

scholarly journals Disrupted dynamic functional network connectivity among cognitive control networks in the progression of Alzheimer’s disease

2021 ◽  
Author(s):  
Mohammad S. E. Sendi ◽  
Elaheh Zendehrouh ◽  
Zening Fu ◽  
Jingyu Liu ◽  
Yuhui Du ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Cognitive Control ◽  
Disease Progression ◽  
Brain Network ◽  
Middle Frontal Gyrus ◽  
Functional Network ◽  
Control Network ◽  
Cognitive Control Network

AbstractBackgroundAlzheimer’s disease (AD) is the most common age-related dementia that promotes a decline in memory, thinking, and social skills. The initial stages of dementia can be associated with mild symptoms, and symptom progression to a more severe state is heterogeneous across patients. Recent work has demonstrated the potential for functional network mapping to assist in the prediction of symptomatic progression. However, this work has primarily used static functional connectivity (sFC) from rs-fMRI. Recently, dynamic functional connectivity (dFC) has been recognized as a powerful advance in functional connectivity methodology to differentiate brain network dynamics between healthy and diseased populations.MethodsGroup independent component analysis was applied to extract 17 components within the cognitive control network (CCN) from 1385 individuals across varying stages of AD symptomology. We estimated dFC among 17 components within the CCN, followed by clustering the dFCs into 3 recurring brain states and then estimated a hidden Markov model and the occupancy rate for each subject. Finally, we investigated the link between CCN dFC connectivity features with AD progression.ResultsProgression of AD symptoms were associated with increases in connectivity within the middle frontal gyrus. Also, the AD with mild and severer symptoms showed less connectivity within the inferior parietal lobule and between this region with the rest of CCN. Finally, comparing with mild dementia, we found that the normal brain spends significantly more time in a state with lower within middle frontal gyrus connectivity and higher connectivity between the hippocampus and the rest of CCN, highlighting the importance of assessing the dynamics of brain connectivity in this disease.ConclusionOur results suggest that AD progress not only alters the CCN connectivity strength but also changes the temporal properties in this brain network. This suggests the temporal and spatial pattern of CCN as a biomarker that differentiates different stages of AD.Impact StatementBy assuming that functional connectivity is static over time, many of previous studies have ignored the brain dynamic in Alzheimer’s disease progression. Here, a longitudinal resting-state functional magnetic resonance imaging data are used to explore the temporal changes of functional connectivity in the cognitive control network in Alzheimer’s disease progression. The result of this study would increase our understanding about the underlying mechanisms of Alzheimer’s Disease and help in finding future treatment of this neurological disorder.

scholarly journals Functional connectivity between the entorhinal and posterior cingulate cortices associated with navigation impairment following path integration in at-genetic-risk Alzheimer’s disease

2019 ◽  
Author(s):  
Gillian Coughlan ◽  
Peter Zhukovsky ◽  
Vaisakh Puthusseryppady ◽  
Rachel Gillings ◽  
Anne-Marie Minihane ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Genetic Risk ◽  
Path Integration ◽  
Amyloid Plaque ◽  
Cingulate Cortex ◽  
Posterior Cingulate Cortex ◽  
Classification Model ◽  
Posterior Cingulate

ABSTRACTNavigation processes mediated selectively by the entorhinal cortex (EC) may be impaired in individuals with suspected preclinical Alzheimer’s disease (AD), but the clinical utility of navigation tests to detect such impairments remains to be established. In a sample of 64 individuals (32 e3e3 and 32 e3e4), we tested whether an existing paradigm, the Virtual Supermarket Test (VST), can reliably detect the presence or absence of the APOE e4 allele which accelerates amyloid plaque deposition in the brain. The present study assessed four major navigational processes that are subserved by functionally specialised cell groups located in AD vulnerable regions including the EC and examined the relationship between navigation process and regional functional connectivity (FC) given FC is a marker early AD-related tau seeding. While heading direction and spatial memory were unaffected by at-risk AD, clear altered navigational strategies following path integration were found on the VST in the e3e4 group. The APOE-sensitive VST measure correctly classified 77% of the APOE cohort. Including resting-state FC between the EC and the posterior cingulate cortex, a correlate of the path integration deficit in the APOE e4 group, the classification model increased the accuracy to 85%. Our findings show that at-genetic-risk AD selectively impairs path integration and biases self-reported spatial locations away from the centre and towards the boundary of a virtual environment. Importantly, this impairment is associated with reduced FC between the EC and the posterior cingulate cortex, which in turn informs the neurobiological mechanisms of at-genetic-risk of AD.

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