Connecting Mind-Body Therapy-Mediated Effects to Pathological Features of Alzheimer’s Disease

2020 ◽  
pp. 1-26
Author(s):  
Melanie Hüttenrauch ◽  
José Sócrates Lopez-Noguerola ◽  
Susana Castro-Obregón
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Positive Impact ◽  
Neuropsychiatric Symptoms ◽  
Alternative Interventions ◽  
Positive Effects ◽  
Dementia Patients

Alzheimer’s disease (AD) is a complex, multifactorial neurodegenerative disorder that represents a major and increasing global health challenge. In most cases, the first clinical symptoms of AD are preceded by neuropathological changes in the brain that develop years to decades before their onset. Therefore, research in the last years has focused on this preclinical stage of AD trying to discover intervention strategies that might, if implemented effectively, delay or prevent disease progression. Among those strategies, mind-body therapies such as yoga and meditation have gained increasing interest as complementary alternative interventions. Several studies have reported a positive impact of yoga and meditation on brain health in both healthy older adults and dementia patients. However, the underlying neurobiological mechanisms contributing to these effects are currently not known in detail. More specifically, it is not known whether yogic interventions, directly or indirectly, can modulate risk factors or pathological mechanisms involved in the development of dementia. In this article, we first review the literature on the effects of yogic practices on outcomes such as cognitive functioning and neuropsychiatric symptoms in patients with mild cognitive impairment and dementia. Then, we analyze how yogic interventions affect different risk factors as well as aspects of AD pathophysiology based on observations of studies in healthy individuals or subjects with other conditions than dementia. Finally, we integrate this evidence and propose possible mechanisms that might explain the positive effects of yogic interventions in cognitively impaired individuals.

scholarly journals Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

2021 ◽  
Vol 14 (5) ◽  
pp. 458
Author(s):  
Barbara Miziak ◽  
Barbara Błaszczyk ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Ischemia ◽  
Neurodegenerative Disorder ◽  
Neuropsychiatric Symptoms ◽  
Antidepressant Drugs ◽  
Cancer Drug ◽  
Novel Treatments ◽  
Close Relationship ◽  
Approved Drugs

Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.

scholarly journals MOLECULAR DOCKING STUDIES ON THE THERAPEUTIC TARGETS OF ALZHEIMER'S DISEASE (AChE AND BChE) USING NATURAL BIOACTIVE ALKALOIDS

2016 ◽  
Vol 8 (12) ◽  
pp. 108
Author(s):  
Punabaka Jyothi ◽  
Kuna Yellamma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Neurodegenerative Disorder ◽  
Biological Activities ◽  
Neuropsychiatric Symptoms ◽  
Docking Studies ◽  
Kcal Mole ◽  
Molecular Docking Studies

Objective: Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms, is biochemically characterized by a significant decrease in the brain neurotransmitter Acetylcholine (ACh).Methods: In the present insilico study, six plant bioactive compounds namely Harmol, Vasicine, Harmaline, Harmine, Harmane and Harmalol (from P. Nigellastrum Bunge) were analyzed for their inhibitory role on AChE (Acetylcholinesterase) and BChE (Butyrylcholinesterase) activity by applying the molecular docking studies. Other parameters viz. determination of molecular interaction-based binding affinity values, protein-ligand interactions, Lipinski rule of five, functional properties and biological activities for the above compounds were also calculated by employing the appropriate bioinformatics tools.Results: The results of docking analysis clearly showed that Harmalol has highest binding affinity with AChE (-8.6 kcal/mole) and BChE (-8.0 kcal/mole) but it does not qualified the enzyme inhibitory activity, since it was exerted, and also has least percentage activity on AD and neurodegenerative disease. Whereas, the Harmine has been second qualified binding affinity (-8.4 kcal/mol) and first in other parameters when compared with Harmalol.Conclusion: Based on docking results and other parameters conducted, we are concluding that Harmine is the best compound for further studies to treat AD.Keywords: Alzheimer's disease (AD), Acetylcholinesterase, Butyrylcholinesterase, Lead Molecules

scholarly journals Revisiting the Amyloid Cascade Hypothesis: From Anti-Aβ Therapeutics to Auspicious New Ways for Alzheimer’s Disease

2020 ◽  
Vol 21 (16) ◽  
pp. 5858 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Md. Tanvir Kabir ◽  
Md. Sohanur Rahman ◽  
Tapan Behl ◽  
Philippe Jeandet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Amyloid Β ◽  
Aβ Oligomers ◽  
Aβ Aggregation ◽  
Clinical Benefits

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-β (Aβ), a peptide of 40–42 amino acids. The conversion of Aβ into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aβ accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aβ monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aβ and antagonize Aβ aggregation, or raise Aβ clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aβ which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aβ oligomers have exhibited exciting findings. Nevertheless, Aβ oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aβ monomer or Aβ plaques ought to have displayed valuable clinical benefits. In this article, Aβ-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.

scholarly journals A combined miRNA–piRNA signature to detect Alzheimer’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gaurav Jain ◽  
Anne Stuendl ◽  
Pooja Rao ◽  
Tea Berulava ◽  
Tonatiuh Pena Centeno ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Noncoding Rna ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Replication Cohort ◽  
Small Noncoding Rna ◽  
Human Cerebrospinal Fluid ◽  
Generation Sequencing ◽  
Common Neurodegenerative Disorder

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder causing huge emotional and economic burden to our societies. An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild–cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and Aβ 42/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.

scholarly journals Topological Dissection of Proteomic Changes Linked to the Limbic Stage of Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Erika Velásquez ◽  
Beáta Szeitz ◽  
Jeovanis Gil ◽  
Jimmy Rodriguez ◽  
Miklós Palkovits ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Brain Area ◽  
Disease Classification ◽  
Molecular Heterogeneity ◽  
Braak Stage ◽  
Tissue Samples ◽  
Major Player

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia worldwide. In AD, neurodegeneration spreads throughout different areas of the central nervous system (CNS) in a gradual and predictable pattern, causing progressive memory decline and cognitive impairment. Deposition of neurofibrillary tangles (NFTs) in specific CNS regions correlates with the severity of AD and constitutes the basis for disease classification into different Braak stages (I-VI). Early clinical symptoms are typically associated with stages III-IV (i.e., limbic stages) when the involvement of the hippocampus begins. Histopathological changes in AD have been linked to brain proteome alterations, including aberrant posttranslational modifications (PTMs) such as the hyperphosphorylation of Tau. Most proteomic studies to date have focused on AD progression across different stages of the disease, by targeting one specific brain area at a time. However, in AD vulnerable regions, stage-specific proteomic alterations, including changes in PTM status occur in parallel and remain poorly characterized. Here, we conducted proteomic, phosphoproteomic, and acetylomic analyses of human postmortem tissue samples from AD (Braak stage III-IV, n=11) and control brains (n=12), covering all anatomical areas affected during the limbic stage of the disease (total hippocampus, CA1, entorhinal and perirhinal cortices). Overall, ~6000 proteins, ~9000 unique phosphopeptides and 221 acetylated peptides were accurately quantified across all tissues. Our results reveal significant proteome changes in AD brains compared to controls. Among others, we have observed the dysregulation of pathways related to the adaptive and innate immune responses, including several altered antimicrobial peptides (AMPs). Notably, some of these changes were restricted to specific anatomical areas, while others altered according to disease progression across the regions studied. Our data highlights the molecular heterogeneity of AD and the relevance of neuroinflammation as a major player in AD pathology. Data are available via ProteomeXchange with identifier PXD027173.

The Investigation of Simultaneous EEG and Eye Tracking Characteristics During Fixation Task in Mild Alzheimer’s Disease

2020 ◽  
pp. 155005942093275
Author(s):  
Malihe Moghadami ◽  
Sahar Moghimi ◽  
Ali Moghimi ◽  
Gholam Reza Malekzadeh ◽  
Javad Salehi Fadardi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Eye Tracking ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Alpha Power ◽  
Fixational Eye Movements ◽  
Fixation Task ◽  
Fixation Frequency

Alzheimer’s disease (AD) is a neurodegenerative disorder that occurs many years before the first clinical symptoms. Finding more exact, significant, and valuable criteria or indices for the diagnosis of the mild form of Alzheimer’s disease is very important for clinical and research purposes. Electroencephalography (EEG) and eye tracking biomarkers would provide noninvasive tools for the early detection of AD. Due to the advantages of EEG and eye tracking, in this study, we employed them simultaneously to conduct research on the mild AD. For this purpose, 19 patients with mild AD were compared with 19 gender- and age-matched normal subjects who did not have any history of cognitive or neurological disorders. EEG and eye-tracking data were concurrently collected in both groups in a fixation task. Our results revealed that the total fixation duration was significantly shorter for the AD patients, but their fixation frequency was more than that of the controls. In addition, increased theta power and decreased alpha power were observed in the AD group. Interestingly, there was a statistically significant correlation between fixation frequency and alpha power in the parietal area in the control group. However, this connection was not statistically significant in the AD group. The findings also indicated an elevated coherence in the AD patients in the parieto-occipital area. It is assumed that the AD patients might use the neural compensational processes for the fixation state. This study provides evidence for the simultaneously EEG and eye-tracking changes in the areas, which are involved in the control of the fixational eye movements.

Flavonoids with Potential Anti-Amyloidogenic Effects as Therapeutic Drugs for Treating Alzheimer’s Disease

2021 ◽  
pp. 1-29
Author(s):  
Qixin Wang ◽  
Xiaofang Dong ◽  
Ran Zhang ◽  
Changqi Zhao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Aging ◽  
Positive Impact ◽  
Amyloid Β ◽  
The Elderly ◽  
Favorable Effect ◽  
Amyloid Β Protein ◽  
Physical And Mental Health ◽  
Dementia Patients

Alzheimer’s disease (AD) is a central neurodegenerative disease generally among the elderly; it accounts for approximately 50–75%of total cases of dementia patients and poses a serious threat to physical and mental health. Currently available treatments for AD mainly relieves its symptoms, and effective therapy is urgently needed. Deposition of amyloid-β protein in the brain is an early and invariant neuropathological feature of AD. Currently the main efforts in developing anti-AD drugs focus on anti-amyloidogenic therapeutics that prevent amyloid-β production or aggregation and decrease the occurrence of neurotoxic events. The results of an increasing number of studies suggest that natural extracts and phytochemicals have a positive impact on brain aging. Flavonoids belong to the broad group of polyphenols and recent data indicate a favorable effect of flavonoids on brain aging. In this review, we collect relevant discoveries from 1999 to 2021, discuss 75 flavonoids that effectively influence AD pathogenesis, and summarize their functional mechanisms in detail. The data we have reviewed show that, these flavonoids belong to various subclasses, including flavone, flavanone, biflavone, etc. Our results provide a reference for further study of the effects of flavonoids on AD and the progress of anti-AD therapy.

scholarly journals Vascular risk factors and neuropsychiatric symptoms in Alzheimer's disease: the Cache County Study

2013 ◽  
Vol 29 (2) ◽  
pp. 153-159 ◽  
Author(s):  
Martin Steinberg ◽  
Kyle Hess ◽  
Chris Corcoran ◽  
Michelle M. Mielke ◽  
Maria Norton ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychiatric Symptoms ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Cache County

Potentially modifiable factors associated with agitation and aggression in Alzheimer’s disease: results of the ICTUS study

2019 ◽  
Vol 31 (10) ◽  
pp. 1509-1516 ◽  
Author(s):  
Adelaide de Mauleon ◽  
Maria Soto ◽  
Pierre Jean Ousset ◽  
Fati Nourhashemi ◽  
Benoit Lepage ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Affective Disorder ◽  
Positive Impact ◽  
Neuropsychiatric Symptoms ◽  
Cognitive Status ◽  
Community Dwelling ◽  
Factors Associated ◽  
Modifiable Factors ◽  
The Impact

ABSTRACTObjectives:To study potentially modifiable factors associated with the severity of agitation or aggression (A/A) symptoms among Alzheimer’s disease (AD) patients.Design:Data from the Impact of Cholinergic Treatment Use (ICTUS) study, European longitudinal prospective observational study.Setting:Community dwelling outpatients included in 29 European memory clinics.Participants:1375 participants with probable AD (Mini-Mental State Examination score of 10–26) with an informal caregiver.Measurements:At baseline and twice yearly over the two-year follow-up, patients underwent comprehensive clinical and neuropsychological assessments: sociodemographic data, cognitive status, functional impairment, and assessment of neuropsychiatric symptoms based on Neuro-Psychiatric Inventory (NPI). The ZARIT scale assessed the caregiver’s burden. The variable of interest was the severity of the item of A/A of the NPI. To study factors associated to the severity of A/A symptoms six months later, a multivariate mixed regression model was used.Results:Frequency of A/A symptom varied from 30% to 34% at each visit. Two factors were found to be independently associated with the severity of A/A: (1) the presence of affective disorder (anxiety, depression, and/or irritability) that increased the severity of the A/A by 0.89 point (coefficient:0.89; 95% Confidence Interval (CI) = [0.48,1.30], p < 0.001), and (2) a severe caregiver burden that increased the severity of the A/A by 1.08 point (coefficient:1.08; 95% CI = [0.69,1.47], p < 0.001).Conclusion:Research should evaluate whether the identification and treatment of an affective disorder along with the evaluation and optimal management of the caregiver would have a positive impact on the course of A/A in mild to moderate AD patients.

scholarly journals Etiological Pattern of Dementia in Patients Attending Dementia Clinic in a Referal Hospital

2014 ◽  
Vol 30 (2) ◽  
pp. 77-83
Author(s):  
Md Masud Rana ◽  
Imran Sarker ◽  
Md Shahadat Hossain ◽  
Md Rezaul Karim Khan ◽  
Md Rafiqul Islam ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Potential Risk ◽  
Cognitive Abilities ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Dementia Patients ◽  
Potential Risk Factors

Background and objectives: Dementia is characterized by loss of or decline in memory and other cognitive abilities and reduces the lifespan of affected people. The number of people with Alzheimer’s Disease and other dementias is increasing every year because of the steady growth in the older population and stable increment in life expectancy and it is expected to increase two-fold by 2030 and three-fold by 2050.In addition to Alzheimer’s disease there are so many reversible and irreversible causes of dementia. This study was aimed to explore the different etiological factors related to dementia patients. Risk factors for dementia, co-morbid conditions were also included. Methods: This cross sectional study was carried out from 2009 to 2014 at dementia clinic (OPD), department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU). A total number of 166 dementia patients, as diagnosed by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and confirmed by Mini Mental State Examination(MMSE) score were recruited in this study. Diagnosis of specific type of dementia was made on the basis of established criteria. Results: Alzheimer’s disease(32.5%) and Vascular dementia(31.9%) were the most common etiological factor followed by Mixed dementia(19.9%), PD with dementia(8.4%) and others(7.2%) like hypothyroidism, head injury, epilepsy etc. Increasing age, hypertension, diabetes mellitus, dyslipidemia, IHD, smoking are potential risk factors for dementia. Conclusion: This study concludes Alzheimer’s disease and Vascular dementia are almost equally occurring dementia. There are also some potential risk factors for development of dementia whose modification can bring a great change in dementia treatment and functional outcome of this group of elderly people of Bangladesh. Bangladesh Journal of Neuroscience 2014; Vol. 30 (2): 77-83

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