Metformin: A Growing Journey from Glycemic Control to the Treatment of Alzheimer’s Disease and Depression

2020 ◽  
Vol 27 ◽  
Author(s):  
Mohamed El Massry ◽  
Lynn M. Alaeddine ◽  
Leen Ali ◽  
Celine Saad ◽  
Assaad A. Eid
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Injury ◽  
Neurological Disorders ◽  
Wide Spectrum ◽  
Metabolic Stress ◽  
Therapeutic Benefit ◽  
Brain Diseases ◽  
Energy Status ◽  
Therapeutic Benefits

: Metabolic stress, transduced as an altered cellular redox and energy status, presents as the main culprit in many diseases including diabetes. However, its role in the pathology of neurological disorders is still not fully elucidated. Metformin, a biguanide compound, is an FDA approved antidiabetic drug generally used for the treatment of type 2 diabetes. The recently described wide spectrum of action executed by this drug suggests a potential therapeutic benefit in a panoply of disorders. Current studies imply that metformin could play a neuroprotective role by reversing hallmarks of brain injury (metabolic dysfunction, neuronal dystrophy and cellular loss), in addition to cognitive and behavioral alterations that accompany the onset of certain brain diseases such as Alzheimer’s disease (AD) and depression. However, the mechanisms by which metformin exerts its protective effect in neurodegenerative disorders is not yet fully elucidated. The aim of this review is to reexamine the mechanisms through which metformin performs its function while concentrating on its effect on reestablishing homeostasis in a metabolically disturbed milieu. We will also highlight the importance of metabolic stress, not only as a component of many neurological disorders, but also as a primary driving force for neural insult. Of interest, we will explore the involvement of metabolic stress in the pathobiology of AD and depression. The derangement in major metabolic pathways including AMPK, insulin and glucose transporters will be dissected and the potential therapeutic benefits of metformin administration on the reversal of brain injury in such metabolism dependent diseases will be exposed.

scholarly journals Therapeutic benefits of music for three types of neurological disorders: an fNIRS study protocol for controlled trial in Dalian, China, Part 1 – Parkinson’s Disease

2020 ◽  
Author(s):  
Lanlan Pu ◽  
Nauman Khalid Qureshi ◽  
Joanne Ly ◽  
Bingwei Zhang ◽  
Fengyu Cong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Major Depression ◽  
Neuronal Activity ◽  
Neurological Disorders ◽  
Finger Tapping ◽  
Therapeutic Effects ◽  
Therapeutic Benefits

Abstract Background: Music therapy improves neuronal activity and connectivity of healthy persons and patients with clinical symptoms of neurological diseases like Parkinson’s Disease, Alzheimer’s Disease, and Major Depression. Despite the plethora of publications that have reported the positive effects of music interventions, little is known about how music improves neuronal activity and connectivity in afflicted patients. In this three-part series of studies, each of the three neurological disorders – (1) Parkinson’s Disease, (2) Alzheimer’s Disease, and (3) Major Depression – will be treated individually in detail. Methods: For patients suffering from Parkinson’s Disease (PD), we propose a daily 25-minute music-based synchronous finger tapping (SFT) intervention for 8-weeks. Participants will be each split into two groups: an intervention group and a control arm. Assessment of finger tapping performances, the Unified Parkinson’s Disease Rating Scale (UPDRS), an n-back test, the Montreal Cognitive Assessment (MoCA), as well as oxygenated- (HbO 2 ), deoxygenated- hemoglobin (HbR), and total hemoglobin activation collected by functional near-infrared spectroscopy (fNIRS) will be measured at baseline, week 4 (during), week 8 (post), and week 12 (retention) of the study. Data collected from the two PD groups will be compared to baseline performances from healthy controls.Discussion: The trial study investigates the cortical neuronal activity and therapeutic effects associated with an auditory external cue used to induce automatic and implicit synchronous finger tapping in patients diagnosed with PD. The extent to which the intervention is effective may be dependent on the severity of the disease.

scholarly journals Long-term Cognitive Impairment after Critical Illness – Definition, Incidence, Pathophysiology and Hypothesis of Neurotrophic Treatment

2015 ◽  
Vol 10 (2) ◽  
pp. 195
Author(s):  
Ignacio J Previgliano ◽  
Bader Andres ◽  
Pawel J Ciesielczyk ◽  
◽  
◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Critical Illness ◽  
Neurovascular Unit ◽  
Public Health Problem ◽  
Brain Diseases

Cognitive impairment after critical illness (CIACI) is a frequent consequence of serious disease or injury that has been reported in as many as 66 % of patients, 3 months after an illness requiring intensive care unit hospitalisation. The condition has been recognised only within the past 15 years and its pathological mechanisms are, as yet, incompletely understood. The neurological changes and cellular and inflammatory processes of CIACI overlap with those of stroke, traumatic brain injury and neurodegenerative disorders. Patients also show brain atrophy, which worsens with the duration of intensive care unit stay. Risk factors associated with CIACI include depression, biomarkers of Alzheimer’s disease (e.g. apolipoprotein E), delirium, exposure to some drugs (e.g. fentanyl, morphine and propofol) and intubation. Current strategies to prevent or treat CIACI include treatments to reduce agitation and delirium and physical and mental rehabilitation including cognitive therapy. Many brain diseases and injuries affect the functioning of the neurovascular unit (NVU), which constitutes the key cellular building block of the blood–brain barrier (BBB). CIACI is believed to affect the integrity of the NVU and it is among the potential targets for therapy. Neurotrophic factors (NTFs), such as brain-derived neurotrophic factor (BDNF) are known to play an important role in neurogenesis, maintenance of NVU structure and neuronal repair after disease and injury. This led to the development of strategies including the NTF-preparation (Cerebrolysin®), which is effective as a post-stroke therapy and has potential in the treatment of Alzheimer’s disease and brain injury as well as CIACI. There are currently no proven treatments for CIACI; improved understanding of the condition and further evaluation of NTFs may lead to effective treatments, which are vital to tackle this increasingly serious public health problem.

Cognitive control constrains memory attributions

2019 ◽  
Vol 42 ◽  
Author(s):  
Colleen M. Kelley ◽  
Larry L. Jacoby
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Control

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.

scholarly journals Application of deep learning in detecting neurological disorders from magnetic resonance images: a survey on the detection of Alzheimer’s disease, Parkinson’s disease and schizophrenia

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Manan Binth Taj Noor ◽  
Nusrat Zerin Zenia ◽  
M Shamim Kaiser ◽  
Shamim Al Mamun ◽  
Mufti Mahmud
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Deep Learning ◽  
Magnetic Resonance ◽  
Neurological Disorders ◽  
Magnetic Resonance Images ◽  
Future Research ◽  
Comparative Performance

Abstract Neuroimaging, in particular magnetic resonance imaging (MRI), has been playing an important role in understanding brain functionalities and its disorders during the last couple of decades. These cutting-edge MRI scans, supported by high-performance computational tools and novel ML techniques, have opened up possibilities to unprecedentedly identify neurological disorders. However, similarities in disease phenotypes make it very difficult to detect such disorders accurately from the acquired neuroimaging data. This article critically examines and compares performances of the existing deep learning (DL)-based methods to detect neurological disorders—focusing on Alzheimer’s disease, Parkinson’s disease and schizophrenia—from MRI data acquired using different modalities including functional and structural MRI. The comparative performance analysis of various DL architectures across different disorders and imaging modalities suggests that the Convolutional Neural Network outperforms other methods in detecting neurological disorders. Towards the end, a number of current research challenges are indicated and some possible future research directions are provided.

Lipidomics and cognitive dysfunction – A Narrative review

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Arpita Chakraborty ◽  
Samir Kumar Praharaj ◽  
R. V. Krishnananda Prabhu ◽  
M. Mukhyaprana Prabhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Vascular Dementia ◽  
Cognitive Dysfunction ◽  
Neurological Disorders ◽  
Brain Lipids ◽  
Complex Lipids ◽  
Functional Components ◽  
The Brain

AbstractBackgroundMore than half portion of the brain is formed by lipids. They play critical roles in maintaining the brain's structural and functional components. Any dysregulation in these brain lipids can lead to cognitive dysfunction which are associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, vascular dementia etc. Studies have linked lipids with cognitive impairment. But not much has been studied about the complex brain lipids which might play a pivotal role in cognitive impairment. This review aims to highlight the lipidomic profiles in patients with cognitive dysfunction.ResultsForty-five articles were reviewed. These studies show alterations in complex lipids such as sphingolipids, phospholipids, glycolipids and sterols in brain in various neurological disorders such as vascular dementia, Parkinson's and Alzheimer's disease. However, the classes of fatty acids in these lipids involved are different across studies.ConclusionsThere is a need for targeted lipidomics analysis, specifically including sphingolipids in patients with neurodegenerative disorders so as to improve diagnostics as well as management of these disorders.

scholarly journals Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?

2010 ◽  
Vol 11 (5) ◽  
pp. 361-370 ◽  
Author(s):  
Victoria E. Johnson ◽  
William Stewart ◽  
Douglas H. Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Amyloid Β

P3-328: Alzheimer's disease psychosis: Potential therapeutic benefit of pimavanserin, a 5-HT2A inverse agonist

2010 ◽  
Vol 6 ◽  
pp. S548-S548
Author(s):  
Krista McFarland ◽  
Diana L. Price ◽  
Sean A. Gorman ◽  
Robert W. Johnson ◽  
Douglas W. Bonhaus
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Benefit ◽  
Inverse Agonist ◽  
Potential Therapeutic Benefit

Caracole as a Potential Neuroprotective Agent for Neurological Diseases: A Systematic

2021 ◽  
Vol 20 ◽  
Author(s):  
Mohammad Zamanian ◽  
Małgorzata Kujawska ◽  
Marjan Nikbakht Zadeh ◽  
Amin Hassanshahi ◽  
Soudeh Ramezanpour ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Parkinson's Disease ◽  
Brain Injury ◽  
Neurological Diseases ◽  
Antioxidant Systems ◽  
Neuroprotective Agent ◽  
The Impact

Background & objective: Neurological diseases are becoming a significant problem worldwide, with the elderly at a higher risk of being affected. Several researchers have investigated the neuroprotective effects of Carvacrol (CAR) (5-isopropyl-2-methyl phenol). This review systematically surveys the existing literature on the impact of CAR when used as a neuroprotective agent in neurological diseases. Methods: The systematic review involved English articles published in the last ten years obtained from PubMed, Google Scholar, and Scopus databases. The following descriptors were used to search the literature: “Carvacrol” [Title] AND “neuroprotective (neuroprotection)” [Title] OR “stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, seizure, epilepsy [Title]. Results: : A total of 208 articles were retrieved during the search process, but only 20 studies met the eligibility criteria and were included for review. A total of 20 articles were identified, in which the efficacy of CAR was described in experimental models of stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, , epilepsy, and seizure, through motor deficits improvements in neurochemical activity, especially antioxidant systems, reducing inflammation, oxidative stress and apoptosis as well as inhibition of TRPC1 and TRPM7. Conclusion : The data presented in this study support the beneficial impact of CAR on behavioural and neurochemical deficits. CAR benefits accrue because of its anti-apoptotic, antioxidant, and anti-inflammatory properties. Therefore, CAR has emerged as an alternative treatment for neurological disorders based on its properties.

scholarly journals Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer’s Disease

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Manoj Govindarajulu ◽  
Priyanka D. Pinky ◽  
Jenna Bloemer ◽  
Nila Ghanei ◽  
Vishnu Suppiramaniam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Effects ◽  
Therapeutic Potential ◽  
Protein Accumulation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Continuous Increase ◽  
Therapeutic Benefits ◽  
The Brain

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. The continuous increase in the incidence of AD with the aged population and mortality rate indicates the urgent need for establishing novel molecular targets for therapeutic potential. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists such as rosiglitazone and pioglitazone reduce amyloid and tau pathologies, inhibit neuroinflammation, and improve memory impairments in several rodent models and in humans with mild-to-moderate AD. However, these agonists display poor blood brain barrier permeability resulting in inadequate bioavailability in the brain and thus requiring high dosing with chronic time frames. Furthermore, these dosing levels are associated with several adverse effects including increased incidence of weight gain, liver abnormalities, and heart failure. Therefore, there is a need for identifying novel compounds which target PPARγ more selectively in the brain and could provide therapeutic benefits without a high incidence of adverse effects. This review focuses on how PPARγ agonists influence various pathologies in AD with emphasis on development of novel selective PPARγ modulators.

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