REVISITING THE CHOLINERGIC HYPOTHESIS IN ALZHEIMER’S DISEASE: EMERGING EVIDENCE FROM TRANSLATIONAL AND CLINICAL RESEARCH

2018 ◽  
pp. 1-14
Author(s):  
H. Hampel ◽  
M.-M. Mesulam ◽  
A.C. Cuello ◽  
A.S. Khachaturian ◽  
A. Vergallo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cholinergic System ◽  
Scientific Evidence ◽  
Cholinergic Innervation ◽  
Cholinergic Hypothesis ◽  
Neuroimaging Data ◽  
Interacting Systems

Scientific evidence collected over the past 4 decades suggests that a loss of cholinergic innervation in the cerebral cortex of patients with Alzheimer’s disease is an early pathogenic event correlated with cognitive impairment. This evidence led to the formulation of the “Cholinergic Hypothesis of AD” and the development of cholinesterase inhibitor therapies. Although approved only as symptomatic therapies, recent studies suggest that long-term use of these drugs may also have disease-modifying benefits. A Cholinergic System Workgroup reassessed the role of the cholinergic system on AD pathogenesis in light of recent data, including neuroimaging data charting the progression of neurodegeneration in the cholinergic system and suggesting that cholinergic therapy may slow brain atrophy. Other pathways that contribute to cholinergic synaptic loss and their effect on cognitive impairment in AD were also reviewed. These studies indicate that the cholinergic system as one of several interacting systems failures that contribute to AD pathogenesis.

scholarly journals Synaptic Plasticity and Oscillations in Alzheimer’s Disease: A Complex Picture of a Multifaceted Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Yuniesky Andrade-Talavera ◽  
Antonio Rodríguez-Moreno
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Neuronal Network ◽  
Brain Plasticity ◽  
Network Dynamics ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Neuronal Network Dynamics

Brain plasticity is widely accepted as the core neurophysiological basis of memory and is generally defined by activity-dependent changes in synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD). By using diverse induction protocols like high-frequency stimulation (HFS) or spike-timing dependent plasticity (STDP), such crucial cognition-relevant plastic processes are shown to be impaired in Alzheimer’s disease (AD). In AD, the severity of the cognitive impairment also correlates with the level of disruption of neuronal network dynamics. Currently under debate, the named amyloid hypothesis points to amyloid-beta peptide 1–42 (Aβ42) as the trigger of the functional deviations underlying cognitive impairment in AD. However, there are missing functional mechanistic data that comprehensively dissect the early subtle changes that lead to synaptic dysfunction and subsequent neuronal network collapse in AD. The convergence of the study of both, mechanisms underlying brain plasticity, and neuronal network dynamics, may represent the most efficient approach to address the early triggering and aberrant mechanisms underlying the progressive clinical cognitive impairment in AD. Here we comment on the emerging integrative roles of brain plasticity and network oscillations in AD research and on the future perspectives of research in this field.

scholarly journals Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

2011 ◽  
Vol 198 (5) ◽  
pp. 351-356 ◽  
Author(s):  
Orestes V. Forlenza ◽  
Breno S. Diniz ◽  
Márcia Radanovic ◽  
Franklin S. Santos ◽  
Leda L. Talib ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Lithium Treatment ◽  
Amnestic Mild Cognitive Impairment ◽  
Disease Assessment ◽  
Short Term Treatment ◽  
Disease Modifying

BackgroundTwo recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment.AimsTo evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).MethodForty-five participants with aMCI were randomised to receive lithium (0.25–0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ42), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392.ResultsLithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.ConclusionsThe present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.

Citicoline in the Treatment of Mild Cognitive Impairment in Blood Relatives of Patients with Alzheimer’s Disease: Immediate and Long-Term Effects of Course Therapy

Psychiatry ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 42-51
Author(s):  
N. D. Seleznеva ◽  
I. F. Roshchina ◽  
E. V. Ponomareva ◽  
S. Iv. Gavrilova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Functioning ◽  
Cognitive Dysfunction ◽  
Therapeutic Effects ◽  
Long Term Effects ◽  
Voluntary Attention

The aim was to study immediate and long-term (post-therapeutic) effects of a three-month course of therapy with citicoline in 1st-degree relatives of patients with Alzheimer’s disease (AD). All the included relatives of patients with AD revealed signs of minimal cognitive dysfunction (MCD) and mild cognitive decline syndrome (MCI — Mild Cognitive Impairment, ICD-10 code F06.7). Study participants: the study involved 90 first-degree relatives: 24 with MCI and 66 with MCD. Study design: an open-label comparative multidisciplinary study of the six-month dynamics of cognitive functioning of two groups of relatives who received a three-month course of citicoline therapy. The baseline indicators of the cognitive functioning of relatives with MCI syndrome and MKD were compared with the indicators at the end of the three-month course of therapy with citicoline at a daily dose of 1000 mg as well as 3 months after the end of the course of treatment. Methods: clinical, psychopathological, neuropsychological, psychometric, genetic, statistical ones. Results: а significant positive effect of the course therapy with citicoline on the cognitive impairment of 1st degree AD-patients’ relatives with minimal cognitive dysfunction and more pronounced cognitive impairments met the diagnostic criteria for MCI syndrome has been found. A significantly greater value of both immediate and long-term therapeutic effect of MKD compared with MCI in relatives was established by psychometric and neuropsychological indicators characterizing voluntary memorization of verbal and visual stimuli, optical and spatial activity, voluntary attention, and associative verbal thinking. Conclusion: the results of the study can be used as the basis for a model of prevention of the progression of cognitive deficit and the development of dementia in persons with a high risk of developing AD, i.e. in individuals with both genetic risk and signs of cognitive impairment.

scholarly journals Involvement of Cholinergic, Adrenergic, and Glutamatergic Network Modulation with Cognitive Dysfunction in Alzheimer’s Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2283
Author(s):  
Yu-Jung Cheng ◽  
Chieh-Hsin Lin ◽  
Hsien-Yuan Lane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Early Stage ◽  
Amyloid Β ◽  
Tau Proteins ◽  
And Oxidative Stress

Alzheimer’s disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. The number of AD cases has been rapidly growing worldwide. Several the related etiological hypotheses include atypical amyloid β (Aβ) deposition, neurofibrillary tangles of tau proteins inside neurons, disturbed neurotransmission, inflammation, and oxidative stress. During AD progression, aberrations in neurotransmission cause cognitive decline—the main symptom of AD. Here, we review the aberrant neurotransmission systems, including cholinergic, adrenergic, and glutamatergic network, and the interactions among these systems as they pertain to AD. We also discuss the key role of N-methyl-d-aspartate receptor (NMDAR) dysfunction in AD-associated cognitive impairment. Furthermore, we summarize the results of recent studies indicating that increasing glutamatergic neurotransmission through the alteration of NMDARs shows potential for treating cognitive decline in mild cognitive impairment or early stage AD. Future studies on the long-term efficiency of NMDA-enhancing strategies in the treatment of AD are warranted.

P1-260: Propofol anesthesia reduces long-term cognitive impairment due to surgery in the 3xTgAD murine model of Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_5) ◽  
pp. P196-P197
Author(s):  
Feras Mardini ◽  
Mack Arroliga ◽  
Junxia Tang ◽  
Roderic Eckenhoff ◽  
Maryellen Eckenhoff
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Murine Model ◽  
Model Of Alzheimer’S Disease

scholarly journals Prediction and Modeling of Neuropsychological Scores in Alzheimer’s Disease Using Multimodal Neuroimaging Data and Artificial Neural Networks

2022 ◽  
Vol 15 ◽  
Author(s):  
Seyed Hani Hojjati ◽  
Abbas Babajani-Feremi ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Neural Networks ◽  
Alzheimer's Disease ◽  
Artificial Neural Networks ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Angular Gyrus ◽  
Multimodal Neuroimaging ◽  
Non Linear ◽  
Neuroimaging Data

Background: In recent years, predicting and modeling the progression of Alzheimer’s disease (AD) based on neuropsychological tests has become increasingly appealing in AD research.Objective: In this study, we aimed to predict the neuropsychological scores and investigate the non-linear progression trend of the cognitive declines based on multimodal neuroimaging data.Methods: We utilized unimodal/bimodal neuroimaging measures and a non-linear regression method (based on artificial neural networks) to predict the neuropsychological scores in a large number of subjects (n = 1143), including healthy controls (HC) and patients with mild cognitive impairment non-converter (MCI-NC), mild cognitive impairment converter (MCI-C), and AD. We predicted two neuropsychological scores, i.e., the clinical dementia rating sum of boxes (CDRSB) and Alzheimer’s disease assessment scale cognitive 13 (ADAS13), based on structural magnetic resonance imaging (sMRI) and positron emission tomography (PET) biomarkers.Results: Our results revealed that volumes of the entorhinal cortex and hippocampus and the average fluorodeoxyglucose (FDG)-PET of the angular gyrus, temporal gyrus, and posterior cingulate outperform other neuroimaging features in predicting ADAS13 and CDRSB scores. Compared to a unimodal approach, our results showed that a bimodal approach of integrating the top two neuroimaging features (i.e., the entorhinal volume and the average FDG of the angular gyrus, temporal gyrus, and posterior cingulate) increased the prediction performance of ADAS13 and CDRSB scores in the converting and stable stages of MCI and AD. Finally, a non-linear AD progression trend was modeled to describe the cognitive decline based on neuroimaging biomarkers in different stages of AD.Conclusion: Findings in this study show an association between neuropsychological scores and sMRI and FDG-PET biomarkers from normal aging to severe AD.

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