Mapping of impaired functional connectivity during memory phases in Alzheimer's disease and its association with cortical β-amyloid

2020 ◽  
Author(s):  
Binyin Li ◽  
Miao Zhang ◽  
Guanyu Ye ◽  
Liche Zhou ◽  
Guiying He ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Memory Performance ◽  
Network Connectivity ◽  
Posterior Cingulate Cortex ◽  
Frontoparietal Network ◽  
Β Amyloid ◽  
The Relationship ◽  
Retrieval Phase

Abstract Background: Amnesia in Alzheimer's disease (AD) could be due to disrupted encoding, consolidation dysfunction, or an impairment in the retrieval of stored memory information. The different memory phases relate with different parts of functional brain systems. Methods: We combine task functional magnetic resonance imaging and amyloid positron emission tomography in 72 participants (36 AD and 36 controls), to investigate the relationship between memory performance, memory phase-locked functional connectivity, and cortical β-amyloid deposition.Results: We found that AD was mainly characterized by decreased functional connectivity in a new data-driven Network composed of regions from default mode network, limbic network and frontoparietal network during the memory maintenance and retrieval phase. Within the Network, AD had more regions with reduced connectivity during the retrieval phase than other phases, locating mainly in the medial prefrontal cortex, posterior cingulate cortex, middle temporal and inferior parietal cortex of left hemisphere. Furthermore, functional connectivity in the Network related to memory performance. Crucially, the magnitude of the Network connectivity reduction during retrieval negatively correlated with mean cortical β-amyloid, and this relationship mediated the relationship between cortical β-amyloid and memory performance.Conclusions: Our findings show that memory deficiency in AD relates with decreased connectivity in specific network and cortical β-amyloid only during retrieval phase. These findings help to map impaired functional connectivity during memory phases and explain the relationship between memory deficiency and cortical β-amyloid.

scholarly journals Amyloid-Beta Influences Memory via Functional Connectivity During Memory Retrieval in Alzheimer's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Binyin Li ◽  
Miao Zhang ◽  
Ikbeom Jang ◽  
Guanyu Ye ◽  
Liche Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Memory Retrieval ◽  
Memory Performance ◽  
Network Connectivity ◽  
Memory Phase ◽  
Β Amyloid ◽  
The Relationship ◽  
Retrieval Phase

Objective: Amnesia in Alzheimer's disease (AD) appears early and could be caused by encoding deficiency, consolidation dysfunction, and/or impairment in the retrieval of stored memory information. The relationship between AD pathology biomarker β-amyloid and memory dysfunction is unclear.Method: The memory task functional MRI and amyloid PET were simultaneously performed to investigate the relationship between memory performance, memory phase-related functional connectivity, and cortical β-amyloid deposition. We clustered functional networks during memory maintenance and compared network connectivity between groups in each memory phase. Mediation analysis was performed to investigate the mediator between β-amyloid and related cognitive performance.Results: Alzheimer's disease was primarily characterized by decreased functional connectivity in a data-driven network composed of an a priori default mode network, limbic network, and frontoparietal network during the memory maintenance (0.205 vs. 0.236, p = 0.04) and retrieval phase (0.159 vs. 0.183, p = 0.017). Within the network, AD had more regions with reduced connectivity during the retrieval than the maintenance and encoding phases (chi-square p = 0.01 and < 0.001). Furthermore, the global cortical β-amyloid negatively correlated with network connectivity during the memory retrieval phase (R = – 0.247, p = 0.032), with this relationship mediating the effect of cortical β-amyloid on memory performance (average causal mediation effect = – 0.05, p = 0.035).Conclusion: We demonstrated that AD had decreased connectivity in specific networks during the memory retrieval phase. Impaired functional connectivity during memory retrieval mediated the adverse effect of β-amyloid on memory. These findings help to elucidate the involvement of cortical β-amyloid (Aβ) in the memory performance in the early stages of AD.

MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Western Blot ◽  
Mrna Expression ◽  
Cognitive Deficits ◽  
Protein Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

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 The relationship of topographical memory performance to regional neurodegeneration in Alzheimer's disease

2012 ◽  
Vol 4 ◽  
Author(s):  
George Pengas ◽  
Guy B. Williams ◽  
Julio Acosta-Cabronero ◽  
Tom W. J. Ash ◽  
Young T. Hong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Performance ◽  
Relationship Of ◽  
The Relationship

scholarly journals The Relationship between Neuropsychiatric Symptoms and Default-Mode Network Connectivity in Alzheimer’s Disease

2020 ◽  
Vol 17 (7) ◽  
pp. 662-666 ◽  
Author(s):  
Jung Suk Lee ◽  
Jong Hun Kim ◽  
Seon-Koo Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Medial Prefrontal Cortex ◽  
Neuropsychiatric Symptoms ◽  
Neuropsychiatric Inventory ◽  
Montreal Neurological Institute ◽  
Default Mode ◽  
The Relationship

Objective Neuropsychiatric symptoms of dementia are prevalent and extremely burdening for the patient and caregivers, but the underlying mechanism of these symptoms has not been investigated. This study aimed to investigate the relationship between neuropsychiatric symptoms and default-mode functional connectivity in Alzheimer’s disease.Methods Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. Functional magnetic resonance imaging was conducted on seventy patients with Alzheimer’s disease during rest. We conducted a seed-based functional connectivity analysis to identify anterior and posterior default-mode networks (DMN). Seeds were the medial prefrontal cortex (Montreal Neurological Institute 12, 51, 36; seed radius=3 mm) for the anterior DMN and the precuneus (Montreal Neurological Institute -6, -63, 27; seed radius=3 mm) for the posterior DMN We then correlated the scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective, and psychosis syndrome) with maps of connectivity in the default-mode network.Results There was a significant correlation between decreased connectivity in the medial prefrontal cortex of the anterior defaultmode network and hyperactivity (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) syndrome (p<0.05, family wise error cluster-level corrected).Conclusion Our study demonstrated that hyperactivity syndrome is related to hypoconnected default-mode network in Alzheimer’s disease. This finding suggests that specific network alterations are associated with certain neuropsychiatric syndromes.

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