scholarly journals Gamma Oscillations in Alzheimer’s Disease and Their Potential Therapeutic Role

2021 ◽  
Vol 15 ◽  
Author(s):  
Artemis Traikapi ◽  
Nikos Konstantinou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Potential Role ◽  
Neurodegenerative Disorder ◽  
Brain Activity ◽  
Sensory Stimulation ◽  
Gamma Oscillations ◽  
Potential Therapeutic Role ◽  
Modifying Effect

Despite decades of research, Alzheimer’s Disease (AD) remains a lethal neurodegenerative disorder for which there are no effective treatments. This review examines the latest evidence of a novel and newly introduced perspective, which focuses on the restoration of gamma oscillations and investigates their potential role in the treatment of AD. Gamma brain activity (∼25–100 Hz) has been well-known for its role in cognitive function, including memory, and it is fundamental for healthy brain activity and intra-brain communication. Aberrant gamma oscillations have been observed in both mice AD models and human AD patients. A recent line of work demonstrated that gamma entrainment, through auditory and visual sensory stimulation, can effectively attenuate AD pathology and improve cognitive function in mice models of the disease. The first evidence from AD patients indicate that gamma entrainment therapy can reduce loss of functional connectivity and brain atrophy, improve cognitive function, and ameliorate several pathological markers of the disease. Even though research is still in its infancy, evidence suggests that gamma-based therapy may have a disease-modifying effect and has signified a new and promising era in AD research.

scholarly journals Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction

2021 ◽  
pp. 1-16
Author(s):  
Wei Wei ◽  
Yinghua Liu ◽  
Chunling Dai ◽  
Narjes Baazaoui ◽  
Yunn-Chyn Tung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Early Development ◽  
Neurodegenerative Disorder ◽  
Synaptic Dysfunction ◽  
Early Postnatal Development ◽  
Wild Type Female

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Cognitive dysfunction and loss of neuronal plasticity are known to begin decades before the clinical diagnosis of the disease. The important influence of congenital genetic mutations on the early development of AD provides a novel opportunity to initiate treatment during early development to prevent the Alzheimer-like behavior and synaptic dysfunction. Objective: To explore strategies for early intervention to prevent Alzheimer’s disease. Methods: In the present study, we investigated the effect of treatment during early development with a ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac-DGGLAG-NH2) on cognitive function and synaptic plasticity in 3xTg-AD transgenic mouse model of AD. 3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or as a control with vehicle diet, and cognitive function and molecular markers of neuroplasticity were evaluated. Results: P021 treatment during early development prevented cognitive impairment and increased expressions of pCREB and BDNF that activated downstream various signaling cascades such as PLC/PKC, MEK/ERK and PI3K/Akt, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice. Conclusion: These findings indicate that treatment with the neurotrophic peptide mimetic such as P021 during early development can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial AD and related tauopathies.

scholarly journals Effects of gamma sensory stimulation on cognitive function in Alzheimer’s disease patients

2021 ◽  
Vol 17 (S6) ◽  
Author(s):  
Aylin Cimenser ◽  
Alexandra Konisky ◽  
Mohinish Shukla ◽  
Holly Mrozak ◽  
Jacob Cohen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Sensory Stimulation

A Chronological Review of Potential Disease-Modifying Therapeutic Strategies for Alzheimer's Disease

2020 ◽  
Vol 26 (12) ◽  
pp. 1286-1299 ◽  
Author(s):  
Miren Ettcheto ◽  
Oriol Busquets ◽  
Triana Espinosa-Jiménez ◽  
Ester Verdaguer ◽  
Carme Auladell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Wide Spectrum ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
New Therapeutic Approaches ◽  
Β Protein

: Late-onset Alzheimer’s disease (LOAD) is a neurodegenerative disorder that has become a worldwide health problem. This pathology has been classically characterized for its affectation on cognitive function and the presence of depositions of extracellular amyloid β-protein (Aβ) and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated Tau protein. To this day, no effective treatment has been developed. : Multiple strategies have been proposed over the years with the aim of finding new therapeutic approaches, such as the sequestration of Aβ in plasma or the administration of anti-inflammatory drugs. Also, given the significant role of the insulin receptor in the brain in the proper maintenance of cognitive function, drugs focused on the amelioration of insulin resistance have been proposed as potentially useful and effective in the treatment of AD. In the present review, taking into account the molecular complexity of the disease, it has been proposed that the most appropriate therapeutic strategy is a combinatory treatment of several drugs that will regulate a wide spectrum of the described altered pathological pathways.

scholarly journals EEG Characterization of the Alzheimer’s Disease Continuum by Means of Multiscale Entropies

Entropy ◽  
2019 ◽  
Vol 21 (6) ◽  
pp. 544 ◽  
Author(s):  
Aarón Maturana-Candelas ◽  
Carlos Gómez ◽  
Jesús Poza ◽  
Nadia Pinto ◽  
Roberto Hornero
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Brain Activity ◽  
P Values ◽  
Eeg Data ◽  
High Prevalence ◽  
Average Slope ◽  
The Brain

Alzheimer’s disease (AD) is a neurodegenerative disorder with high prevalence, known for its highly disabling symptoms. The aim of this study was to characterize the alterations in the irregularity and the complexity of the brain activity along the AD continuum. Both irregularity and complexity can be studied applying entropy-based measures throughout multiple temporal scales. In this regard, multiscale sample entropy (MSE) and refined multiscale spectral entropy (rMSSE) were calculated from electroencephalographic (EEG) data. Five minutes of resting-state EEG activity were recorded from 51 healthy controls, 51 mild cognitive impaired (MCI) subjects, 51 mild AD patients (ADMIL), 50 moderate AD patients (ADMOD), and 50 severe AD patients (ADSEV). Our results show statistically significant differences (p-values < 0.05, FDR-corrected Kruskal–Wallis test) between the five groups at each temporal scale. Additionally, average slope values and areas under MSE and rMSSE curves revealed significant changes in complexity mainly for controls vs. MCI, MCI vs. ADMIL and ADMOD vs. ADSEV comparisons (p-values < 0.05, FDR-corrected Mann–Whitney U-test). These findings indicate that MSE and rMSSE reflect the neuronal disturbances associated with the development of dementia, and may contribute to the development of new tools to track the AD progression.

scholarly journals Exploring the Alterations in the Distribution of Neural Network Weights in Dementia Due to Alzheimer’s Disease

Entropy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. 500
Author(s):  
Marcos Revilla-Vallejo ◽  
Jesús Poza ◽  
Javier Gomez-Pilar ◽  
Roberto Hornero ◽  
Miguel Ángel Tola-Arribas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Brain Activity ◽  
Healthy Elderly ◽  
Eeg Data ◽  
Depth Analysis ◽  
Higher Weights ◽  
Functional Brain Activity ◽  
The Impact

Alzheimer’s disease (AD) is a neurodegenerative disorder which has become an outstanding social problem. The main objective of this study was to evaluate the alterations that dementia due to AD elicits in the distribution of functional network weights. Functional connectivity networks were obtained using the orthogonalized Amplitude Envelope Correlation (AEC), computed from source-reconstructed resting-state eletroencephalographic (EEG) data in a population formed by 45 cognitive healthy elderly controls, 69 mild cognitive impaired (MCI) patients and 81 AD patients. Our results indicated that AD induces a progressive alteration of network weights distribution; specifically, the Shannon entropy (SE) of the weights distribution showed statistically significant between-group differences (p < 0.05, Kruskal-Wallis test, False Discovery Rate corrected). Furthermore, an in-depth analysis of network weights distributions was performed in delta, alpha, and beta-1 frequency bands to discriminate the weight ranges showing statistical differences in SE. Our results showed that lower and higher weights were more affected by the disease, whereas mid-range connections remained unchanged. These findings support the importance of performing detailed analyses of the network weights distribution to further understand the impact of AD progression on functional brain activity.

scholarly journals 40Hz sensory stimulation induces gamma entrainment and affects brain structure, sleep and cognition in patients with Alzheimer’s dementia

2021 ◽  
Author(s):  
Diane Chan ◽  
Ho-Jun Suk ◽  
Brennan Jackson ◽  
Noah Pollak Milman ◽  
Danielle Stark ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Functional Connectivity ◽  
Brain Structure ◽  
Sensory Stimulation ◽  
Alzheimer’S Dementia ◽  
Control Group ◽  
Alzheimer's Dementia ◽  
Sleep And Cognition

ABSTRACTNon-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduced Alzheimer’s disease (AD) pathology such as amyloid and tau levels, prevented cerebral atrophy and improved performance during behavioral testing in mouse models of AD. We report data from a randomized, placebo-controlled trial (n = 15) in volunteers with probable mild AD after 4 months of one-hour daily 40Hz sensory stimulation (NCT NCT04055376) to assess safety, compliance, entrainment and possible effects on brain structure, function, sleep activity and cognitive function. 40Hz light and sound GENUS was well-tolerated and compliance was high in both groups. Electroencephalography recordings show that our novel 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD. After 3 months of daily stimulation, the 40Hz GENUS group showed reduced ventricular dilation and stabilization of the hippocampal size compared to the control group. Functional connectivity was found to improve in the default mode network as well as with the medial visual network after 3 months of stimulation. Furthermore, actigraphy recordings show that circadian rhythmicity also improved with 40Hz stimulation. Compared to controls, the active group performed better on the face-name association delayed recall test. These results suggest that 40Hz GENUS can be used safely at home daily and shows favorable outcomes on cognitive function, structure and functional MRI biomarkers of AD-related degeneration. These results support further evaluation of GENUS in larger and longer clinical trials to evaluate its potential as a novel disease modifying therapeutic for Alzheimer’s dementia.ONE SENTENCE SUMMARY40Hz sensory stimulation can safely and efficiently induce entrainment of neural oscillations in patients with mild probable Alzheimer’s disease and may be a novel therapeutic that can prevent brain atrophy while improving functional connectivity, sleep and cognition.

scholarly journals The effect of insomnia on development of Alzheimer’s disease

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Shaghayegh Sadeghmousavi ◽  
Mahsa Eskian ◽  
Farzaneh Rahmani ◽  
Nima Rezaei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sleep Disorders ◽  
Potential Role ◽  
Neurodegenerative Disorder ◽  
Memory Deficits ◽  
Information Recall ◽  
Important Health ◽  
Important Health Issue

Abstract Alzheimer’s disease (AD) is the most common type of dementia and a neurodegenerative disorder characterized by memory deficits especially forgetting recent information, recall ability impairment, and loss of time tracking, problem-solving, language, and recognition difficulties. AD is also a globally important health issue but despite all scientific efforts, the treatment of AD is still a challenge. Sleep has important roles in learning and memory consolidation. Studies have shown that sleep deprivation (SD) and insomnia are associated with the pathogenesis of Alzheimer’s disease and may have an impact on the symptoms and development. Thus, sleep disorders have decisive effects on AD; this association deserves more attention in research, diagnostics, and treatment, and knowing this relation also can help to prevent AD through screening and proper management of sleep disorders. This study aimed to show the potential role of SD and insomnia in the pathogenesis and progression of AD.

scholarly journals Targeting Galectin 3 to Counteract Spike-Phase Uncoupling of Fast-Spiking Interneurons to Gamma Oscillations in Alzheimer’s Disease

2021 ◽  
Author(s):  
Luis Enrique Arroyo-García ◽  
Sara Bachiller ◽  
Antonio Boza-Serrano ◽  
Antonio Rodríguez-Moreno ◽  
Tomas Deierborg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Network ◽  
Neurodegenerative Disorder ◽  
Network Dynamics ◽  
Gamma Oscillations ◽  
Dependent Manner ◽  
Galectin 3 ◽  
Fast Spiking ◽  
5Xfad Mice

Abstract Background: Alzheimer’s disease (AD) is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists. Neuroinflammation is central to the pathology progression, with evidence suggesting that microglia-released galectin 3 (gal3) plays a pivotal role by amplifying neuroinflammation in AD. However, possible involvement of gal3 in the disruption of cognition-relevant neuronal network oscillations typical of AD remains unknown. Methods: Here, we investigate the functional implications of gal3 signaling on cognition-relevant gamma oscillations (30-80 Hz) by performing electrophysiological recordings in hippocampal area CA3 of wild-type (WT) and 5xFAD mice in vitro. Results: Gal3 application decreases gamma oscillation power and rhythmicity in an activity-dependent manner and is accompanied by impairment of cellular dynamics in fast-spiking interneurons (FSN) and pyramidal cells (PCs). We found that gal3-induced disruption is mediated by the gal3-carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139, which also prevents Aβ42-induced degradation of gamma oscillations. Furthermore, we demonstrate that 5xFAD mice lacking gal3 (5xFAD-Gal3KO) exhibit WT-like gamma network dynamics.Conclusions: We report for the first time that gal3 impairs cognition-relevant neuronal network dynamics by spike-phase uncoupling of FSN inducing a network performance collapse. Moreover, our findings suggest gal3 inhibition as a potential therapeutic target to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.

scholarly journals Risk Variants in Three Alzheimer’s Disease Genes Show Association with EEG Endophenotypes

2021 ◽  
pp. 1-15
Author(s):  
Ana Macedo ◽  
Carlos Gómez ◽  
Miguel Ângelo Rebelo ◽  
Jesús Poza ◽  
Iva Gomes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Brain Activity ◽  
Disease Status ◽  
Major Effect ◽  
Disease Genes ◽  
Frequency Bands ◽  
Brain Physiology ◽  
Risk Alleles

Background: Dementia due to Alzheimer’s disease (AD) is a complex neurodegenerative disorder, which much of heritability remains unexplained. At the clinical level, one of the most common physiological alterations is the slowing of oscillatory brain activity, measurable by electroencephalography (EEG). Relative power (RP) at the conventional frequency bands (i.e., delta, theta, alpha, beta-1, and beta-2) can be considered as AD endophenotypes. Objective: The aim of this work is to analyze the association between sixteen genes previously related with AD: APOE, PICALM, CLU, BCHE, CETP, CR1, SLC6A3, GRIN2 β, SORL1, TOMM40, GSK3 β, UNC5C, OPRD1, NAV2, HOMER2, and IL1RAP, and the slowing of the brain activity, assessed by means of RP at the aforementioned frequency bands. Methods: An Iberian cohort of 45 elderly controls, 45 individuals with mild cognitive impairment, and 109 AD patients in the three stages of the disease was considered. Genomic information and brain activity of each subject were analyzed. Results: The slowing of brain activity was observed in carriers of risk alleles in IL1RAP (rs10212109, rs9823517, rs4687150), UNC5C (rs17024131), and NAV2 (rs1425227, rs862785) genes, regardless of the disease status and situation towards the strongest risk factors: age, sex, and APOE ɛ4 presence. Conclusion: Endophenotypes reduce the complexity of the general phenotype and genetic variants with a major effect on those specific traits may be then identified. The found associations in this work are novel and may contribute to the comprehension of AD pathogenesis, each with a different biological role, and influencing multiple factors involved in brain physiology.

Auditory Dysfunction in Alzheimer's Disease

2010 ◽  
Vol 15 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Sridhar Krishnamurti
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Care Setting ◽  
Neurodegenerative Disorder ◽  
Disease Process ◽  
Clinical Protocols ◽  
Speech Language Pathologist ◽  
Auditory Dysfunction

Alzheimer's disease is neurodegenerative disorder which affects a growing number of older adults every year. With an understanding of auditory dysfunction in Alzheimer's disease, the speech-language pathologist working in the health care setting can provide better service to these individuals. The pathophysiology of the disease process in Alzheimer's disease increases the likelihood of specific types of auditory deficits as opposed to others. This article will discuss the auditory deficits in Alzheimer's disease, their implications, and the value of clinical protocols for individuals with this disease.

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