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Protective effects of some medicinal plants from Lamiaceae family against beta-amyloid induced toxicity in PC12 cell
Balali P, Soodi M, Saeidnia S,
Volume 70, Issue 7 (10-2012)
Abstract

Background: Excessive accumulation of beta-amyliod peptide (Aβ), the major component of senile plaques in Alzheimer's disease (AD), causes neuronal cell death through induction of oxidative stress. Therefore, antioxidants may be of use in the treatment of AD. The medicinal plants from the Lamiaceae family have been widely used in Iranian traditional medicine. These plants contain compounds with antioxidant activity and some species in this family have been reported to have neuroprotective properties. In the present study, methanolic extract of seven plants from salvia and satureja species were evaluated for their protective effects against beta-amyloid induced neurotoxicity.
Methods: Aerial parts of the plants were extracted with ethyl acetate and methanol, respectively, by percolation at room temperature and subsequently, methanolic extracts of the plants were prepared. PC12 cells were incubated with different concentrations of the extracts in culture medium 1h prior to incubation with Aβ. Cell toxicity was assessed 24h after addition of Aβ by MTT assay.
Results: Satureja bachtiarica, Salvia officinalis and Salvia macrosiphon methanolic extracts exhibited high protective effects against Aβ induced toxicity (P<0.001). Protective effects of Satureja bachtiarica and Salvia officinalis were dose-dependent.
Conclusion: The main constituents of these extracts are polyphenolic and flavonoid compounds such as rosmarinic acid, naringenin, apigenin and luteolin which have antioxidant properties and may have a role in neuroprotection. Based on neuroprotective effect of these plants against Aβ induced toxicity, we recommend greater attention to their use in the treatment of Alzheimer disease.


The correlation of serum S100β protein levels and hippocampal Seladin-1 gene expression in a rat model of sporadic Alzheimer's disease
Soheila Hosseinzadeh , Maryam Zahmatkesh , Gholam-Reza Hassanzadeh Hassanzadeh , Morteza Karimian , Mansour Heidari , Mahmoud Karami ,
Volume 73, Issue 8 (11-2015)
Abstract

Background: Seladin-1 protein protects the neural cells against amyloid beta toxicity and its expression decreased in vulnerable regions of Alzheimer's disease (AD) brains. On the other hand, changes in serum levels of S100 have been considered as a marker of brain damage in neurodegenerative diseases. Furthermore, this study was carried out to determine the relation between the change profile of serum S100&beta protein levels and hippocampal Seladin-1 gene expression in a rat model of sporadic AD. Methods: In this experimental study that established in Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Science, from March 2011 to April 2013, 72 animals were randomly divided into control, 4, 7, 14, and 21days ICV-STZ/Saline administrated rats. Alzheimer's model was induced by intracerebroventricular (ICV) injections of streptozotocin (STZ) [3 mg/kg] on days 1 and 3. Serum levels of S100&beta and hippocampal Seladin-1 gene expression were evalu-ated in experimental groups. The initial and step-through latencies (STL) were deter-mined using passive avoidance test. Results: Serum levels of S100&beta were significantly different between the STZ-7 day and STZ-14 day groups in comparison with the control, saline and STZ-4 day groups. As well as, there was a significant difference between the STZ-7 day group in comparison with the STZ-14 day and STZ-21 day groups (P=0.0001). Hippocampal Seladin-1 gene expression in STZ-14 day and STZ-21 day groups significantly decreased as compared to the control, saline and STZ-4 day groups (P=0.0001). However, significant correla-tion was detected between serum S100&beta protein decrement and Seladin-1 down regula-tion (P=0.001). Also, the STL was significantly decreased in 21 days ICV-STZ adminis-trated rats as compared to the control or saline groups (P=0.001). Conclusion: Monitoring the changes of serum S100&beta protein levels by relationship with changes in hippocampal Seladin-1 gene expression can be a useful indicator of neu-ronal damage in patients with Alzheimer's disease.


Detection of Alzheimer's disease based on magnetic resonance imaging of the brain using support vector machine model
Mansour Rezaei , Ehsan Zereshki , Hamid Sharini , Mohamad Gharib Salehi , Farhad Naleini ,
Volume 76, Issue 6 (9-2018)
Abstract
Background: Alzheimer's disease (AD) is the most common disorder of dementia, which has not been cured after its occurrence. AD progresses indiscernible, first destroy the structure of the brain and subsequently becomes clinically evident. Therefore, the timely and correct diagnosis of these structural changes in the brain is very important and it can prevent the disease or stop its progress. Nowadays, remark to this fact that magnetic resonance imaging (MRI) provides very useful and detailed information, and due to non-invasiveness, this method has been great interest to the researchers. The aim of this study was diagnosis of AD with MRI by support vector machine model (SVM).
Methods: This is an analytical and modeling research which done in School of Public Health, Kermanshah University of Medical Science, Iran, from February 2017 to November 2017. The data used in this study was a database named Miriad containing brain MRI of 69 individuals (46 Alzheimer's disease and 23 healthy subjects) that was collected at the central hospital in London. Individuals were categorized into two groups of healthy and Alzheimer's disease with two criteria: NINCDS-ADRAD and MMSE (as the golden standard). In this paper SVM model with three linear, binomial and Gaussian kernels was used to distinguish Alzheimer`s disease from healthy individuals.
Results: Finally, SVM model with Gaussian kernel, separated AD and healthy subjects with 88.34% accuracy. The most important Areas for Alzheimer were three Area: Right para hippocampal gyrus, Left para hippocampal gyrus and Right hippocampus. The clinical result of this study is to identify the most important ROI for the diagnosis of Alzheimer's by a clinical specialist. Experts should focus on atrophy in the three Areas.
Conclusion: This study showed that the SVM model with Gaussian RBF kernel can separated AD from healthy subjects by high accuracy. Based on results of this study, can make a software to use in MRI centers for screening AD test by people over the age of 50 years.

Vitamin D level in Alzheimer's disease: a case control study
Vajiheh Aghamollaii , Abbas Tafakhori , Shakila Meshkat , Arezoo Shafieyoun , Amir Salimi ,
Volume 78, Issue 1 (4-2020)
Abstract
Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by a progressive decline of cognitive performance, which has a harmful impact on social activities. AD is the main cause of dementia and loss of functional independence in the elderly. AD is a worldwide concern because of its adverse consequences and expanding prevalence and incidence. Vitamin D is the most common nutritional deficiency worldwide among children and adults. In addition to its classical function of bone metabolism regulation, vitamin D exhibits multiple biological targets mediated by the vitamin D receptor (VDR). Vitamin D is a risk factor for a wide range of diseases and, as a neurosteroid, has an essential role in nervous system development and protection. Vitamin D regulates mechanisms involved in the pathogenesis of AD, including phagocytosis of amyloid-beta plaques, anti-inflammatory action, antioxidant action, regulation of intraneuronal calcium, ischemic zone size reduction, regulation of choline acetyltransferase enzyme and neurotrophic agents. This study aimed to evaluate the association between AD and vitamin D deficiency.
Methods: In this case-control study, 44 Alzheimer’s disease patients (diagnosed based on DSM-IV-TR criteria) compared with 40 patients that had no disease related to vitamin D. This study was performed in the neurology clinics of Roozbeh and Imam Khomeini Hospitals in Tehran, from April to March 2015. The demographic data were collected. After obtaining informed consent, venous blood was taken by clinical staff to measure the level of 25-hydroxyvitamin D3. Statistical analysis was performed on data.
Results: The Mean age was 71.55 years old (69.88 for females and 73.74 for males) in the case group. Mean vitamin D levels were 26.31 ng/ml and 36.41 ng/ml in case and control groups, respectively. Vitamin D level was deficient (< 30 ng/ml) in 75% of patients, of which 23% were severely deficient (< 10 ng/ml). Statistical analysis showed no significant relationship between Alzheimer's disease and vitamin D levels (P=0.057), but when participants categorized into three groups based on serum vitamin D levels (deficient, insufficient, sufficient), we found a significant relationship between them (P=0.019).
Conclusion: Our results confirm the association between vitamin D deficiency and Alzheimer's disease. Vitamin D supplementation should be considered in individuals at risk of Alzheimer's disease to reach sufficient vitamin D level.

Comparison of visual evoked potential changes in patients with alzheimer, vascular dementia and minimal cognitive Impairment with healthy people: a case-control study
Narges Khodaparast, Nazila Malekian, Zahra Vahabi, Davood Fathi, Shahram Oveisgharan, Farzad Fatehi, Siamak Abdi,
Volume 78, Issue 5 (8-2020)
Abstract
Background: Alzheimer dementia as the most common cause of dementia is a chronic, progressive, irreversible and incurable disease. The second most common cause of dementia after Alzheimer is vascular dementia. One of the systems involved in dementia is the visuospatial system and visual evoked potential (VEP) can be one of the diagnostic methods for this disease. Therefore, the present study aims to compare visual evoked potential changes in Alzheimer dementia, vascular dementia and patients with minimally conscious impairment (MCI) with healthy people.
Methods: A case-control study was performed on referred clients to Shariati Hospital, Tehran, Iran, from April 2015 to September 2016. Patients with cognitive impairment went through Montreal cognitive assessment (MOCA) test and divided into three groups of Alzheimer dementia, vascular dementia and patients with minimally conscious impairment. Subjects with normal cognition were included in the control group. The visual evoked potential test was performed on all participants in two Methods: pattern shift visual evoked potential (Ps-VEP) and flash visual evoked potential (f-VEP) and results were compared between groups.
Results: Forty patients were studied in four groups (three patient groups and one control group). 70 percent in Alzheimer group and 60 percent in vascular dementia group had abnormal pattern shift visual evoked potential. Only in Alzheimer group visual evoked potential P100 latency was significantly higher than control group and in other groups, there was no significant difference. Also there was no significant difference between groups in the study of flash visual evoked potential variables including P1, N2, P2 and N3.
Conclusion: This study showed that only Alzheimer was associated with a significant increase in visual evoked potential P100 latency. On the other hand the other hand, there was no significant difference in flash visual evoked potential variables including P1, N2, P2 and N3 between different groups which shows that flash visual evoked potential cannot differentiate between Alzheimer dementia, vascular dementia, patients with minimally conscious impairment and normal people.

The effect of flavonoids in the treatment of Alzheimer’s disease: review article
Adele Jafari, Behrooz Khakpour Taleghani ,
Volume 79, Issue 1 (4-2021)
Abstract
Alzheimer’s disease (AD) is the most prevalent age-related neurodegenerative disorder worldwide, and no cure or prevention has been found for it. Extracellular senile plaque and intracellular neurofibrillary tangles are two important histopathological hallmarks of AD, which are both harmful for the cell. Senile plaques are composed of amyloid beta and neurofibrillary tangles are formed by hyperphosphorylated Tau proteins. In AD, several cellular changes also occur, including oxidative stress, neuroinflammation, accumulation of misfolded proteins, and mitochondrial dysfunction. These events promote neuronal death and finally decline memory and cognition. Lack of success of the available chemical anti-AD therapeutic agents has attracted attention to the concept of the administration of naturally occurring compounds in the treatment of AD. These compounds can be employed as a substitute for the chemical agents or complementary regimens. Several natural products are deemed capable of crossing the blood-brain barrier and are known for their central nervous system-related activity. Among the most important of them are flavonoids. Recent evidence has demonstrated their neuroprotective effects. These plant-derived compounds have strong effects on dementia-induced brain disorders because of their ability to produce antioxidants. Numerous mechanisms have been proposed for flavonoids through which they act for the prevention or recession of the disease process. According to evidence, flavonoids inhibit acetylcholinesterase (AChE), β-secretase (BACE1) and free radicals. They reduce the amyloid-beta toxicity and prevent the formation of neurofibrillary tangles. Also, they help to inhibit apoptosis induced by oxidative stress and neuroinflammation. These products have a role in synaptic plasticity and the generation of new neurons. They can affect various signaling pathways like Extracellular signal-regulated kinase (Erk), Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK). Overall, these processes can prevent the progression of AD and improve cognitive symptoms. In the present paper, the effect of the most important plant-derived flavonoids is briefly reviewed in different models of AD. The mechanism of action and the important signaling pathways in reducing neuroinflammation, apoptosis, and oxidative damage are discussed. It is concluded that despite the beneficial effect of these compounds, future studies are needed before flavonoids can be used as a drug in the treatment of Alzheimer’s disease.
 

Identification of mild cognitive impairment disease using brain functional connectivity and graph analysis in fMRI data
Hasan Mohammadi Kiani , Ahmad Shalbaf, Arash Maghsoudi,
Volume 79, Issue 2 (5-2021)
Abstract
Background: Early diagnosis of patients in the early stages of Alzheimer's, known as mild cognitive impairment, is of great importance in the treatment of this disease. If a patient can be diagnosed at this stage, it is possible to treat or delay Alzheimer's disease. Resting-state functional magnetic resonance imaging (fMRI) is very common in the process of diagnosing Alzheimer's disease. In this study, we intend to separate subjects with mild cognitive impairment from healthy control based on fMRI data using brain functional connectivity and graph theory.
Methods: In this article, which was done from April to November 2020 in Tehran, after pre-processing the fMRI data, 116 brain regions were extracted using an Automated Anatomical Labeling atlas. Then, the functional connectivity matrix between the time signals of 116 brain regions was calculated using Pearson correlation and mutual information methods. Using functional connectivity calculations, the brain graph network was formed, followed by thresholding of the brain connectivity network to keep significant and strong edges while eliminating weaker edges that were likely noise. Finally, 11 global features were extracted from the graph network and after performing statistical analyses and selecting optimal features; the classification of 14 healthy individuals and 11 patients with mild cognitive impairment was performed using a support vector machine classifier.
Results: Calculations were showed that the mutual information algorithm as a functional connectivity method and five global features of the graph network, including average strength, eccentricity, local efficiency, coefficient clustering and transitivity, using the support vector machine classifier achieved the best performance with the accuracy, sensitivity and specificity of 84, 86 and 93 percent, respectively.
Conclusion: Combining the features of brain graph and functional connectivity by the mutual information method with a machine learning approach, based on fMRI imaging analysis, is very effective in diagnosing mild cognitive impairment in the early stages of Alzheimer’s which consequently allows treating or delaying this disease.

Atrophy of hippocampal subfields as a diagnostic biomarker in alzheimer's disease patients and its differentiation from mild cognitive impairment disorders
Yunus Soleymani, Amir Reza Jahanshahi, Davood Khezerloo ,
Volume 80, Issue 11 (2-2023)
Abstract
Background: Atrophy of hippocampal subfields is one of the diagnostic biomarkers of Alzheimer's disease, which has also been observed in many patients with mild cognitive impairment. There is still no clear understanding of the atrophy pattern of hippocampal subfields in Alzheimer's disease and its differentiation from mild cognitive impairment. In this cross-sectional study, hippocampal subfield atrophy in Alzheimer's patients were compared with patients with early (EMCI) and late (LMCI) cognitive impairment and the control group.
Methods: This was a cross-sectional study conducted from September 2021 to September 2022 in the radiology department of Tabriz Paramedical Faculty. MRI images of Alzheimer's patients, EMCI patients, LMCI patients, and normal controls (NCs) were obtained from the ADNI database. Different hippocampus subfields of hippocampal fissure, dentate gyrus head, dentate gyrus body, first cornu ammonis body, cornu ammonis head, subiculum body, and subiculum head were isolated using the hippocampus segmentation tool in FreeSurfer 7.0 software. The volume of all subfields was calculated bilaterally and normalized. The volume difference of each hippocampus subfield between the groups participating in the study and the pair volume difference between the groups was analyzed using the Kruskal-Wallis H Test and post-hoc Dunn's test. The P<0.05 was considered as the significance level.
Results: The most significant volume difference between the four groups participating in the study was related to the whole hippocampus, DG body, subiculum body, and subiculum head subfields (P<0.0001). Also, when examining pairs, the most significant difference was observed between the NC/AD pair (P<0.0001) and the least significant difference between the pair of LMCI/AD group (P<0.05) and in the subfield subiculum body showing the progressive course of hippocampal subfield atrophy with cognitive progress towards Alzheimer's disease.
Conclusion: In most subfields of the hippocampus, a significant difference in atrophy can be seen, increasing the severity of atrophy as the disorder progresses toward Alzheimer's. Such findings can help guide future studies to improve diagnostic performance to identify individuals at high risk of Alzheimer's disease.

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