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Oxidative Medicine and Cellular... 2021Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VD), is responsible for at least 15 to 20 percent of dementia in the elderly. Mitochondrial...
Mitochondrial Protection and Against Glutamate Neurotoxicity via Shh/Ptch1 Signaling Pathway to Ameliorate Cognitive Dysfunction by Kaixin San in Multi-Infarct Dementia Rats.
Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VD), is responsible for at least 15 to 20 percent of dementia in the elderly. Mitochondrial dysfunctions and glutamate neurotoxicity due to chronic hypoperfusion and oxidative stress were regarded as the major risk factors in the pathogenesis. (KXS), a classic prescription of , was applied to treatment for "amnesia" and has been demonstrated to alleviate the cognitive deficit in a variety of dementias, including MID. However, little is known whether mitochondria and glutamate are associated with the protection of KXS in MID treatment. The aim of this study was to investigate the role of KXS in improving the cognitive function of MID rats through strengthening mitochondrial functions and antagonizing glutamate neurotoxicity via the Shh/Ptch1 signaling pathway. Our data showed that KXS significantly ameliorated memory impairment and hippocampal neuron damage in MID rats. Moreover, KXS improved hippocampal mitochondrial functions by reducing the degree of mitochondrial swelling, increasing the mitochondrial membrane potential (MMP), and elevating the energy charge (EC) and ATP content in MID rats. As expected, the concentration of glutamate and the expression of p-NMDAR1 were significantly reduced by KXS in the brain tissue of MID rats. Furthermore, our results showed that KXS noticeably activated the Shh/Ptch1 signaling pathway which was demonstrated by remarkable elevations of Ptch1, Smo, and Gli1 protein levels in the brain tissue of MID rats. Intriguingly, the inhibition of the Shh signaling pathway with cyclopamine significantly inhibited the protective effects of KXS on glutamate-induced neurotoxicity in PC12 cells. To sum up, these findings suggested that KXS protected MID rats from memory loss by rescuing mitochondrial functions as well as against glutamate neurotoxicity through activating Shh/Ptch1 signaling pathway.
Topics: Animals; Cognitive Dysfunction; Dementia, Multi-Infarct; Disease Models, Animal; Drugs, Chinese Herbal; Glutamic Acid; Male; Memory Disorders; Mitochondria; Neurons; Patched-1 Receptor; Rats, Sprague-Dawley; Signal Transduction; Rats
PubMed: 34306310
DOI: 10.1155/2021/5590745 -
Neurologia I Neurochirurgia Polska 2021With newer research-based classification systems, the term Vascular Cognitive Impairment (VCI) is now preferred to vascular dementia. VCI is an umbrella term that...
With newer research-based classification systems, the term Vascular Cognitive Impairment (VCI) is now preferred to vascular dementia. VCI is an umbrella term that includes all forms of cognitive deficits ranging from mild cognitive impairment of vascular origin (VaMCI) to vascular dementia (VaD). The new VCI construct takes into account the fact that in addition to single strategic infarcts, multiple infarcts, and leukoaraiosis, there are other mechanisms of cerebrovascular disease such as chronic hypoperfusion that might account for the pattern of cognitive deficits associated with vascular dementia. The key to defining the spectrum of VCI is neuropsychological testing, bedside or office-based clinical examination, and neuroimaging. The lack of specific cognitive tools that are sufficiently sensitive to detect subtle deficits makes the assessment of cognitive impairment difficult. Prospective cross-sectional and longitudinal studies of VCI from different settings are therefore required. Although there have been few published reports, behavioural and psychological symptoms (BPS) are inherently present in VCI from the onset and during the course of the disease. Besides the type of population (i.e. clinical, community or nursing-home settings), the definition of VCI/VaD and the instruments used, and differences in the prevalence and pattern of BPS between various studies, could be due to other, often unconsidered, factors such as gender, age, education, use of medication and VCI/VaD severity.
Topics: Cognition; Cognitive Dysfunction; Cross-Sectional Studies; Dementia, Vascular; Humans; Prospective Studies
PubMed: 34096014
DOI: 10.5603/PJNNS.a2021.0035 -
IEEE/ACM Transactions on Computational... 2022Hypertension (HT), or high blood pressure is one of the most common and main causes in cardiovascular diseases, which is also related to a series of detrimental diseases...
Hypertension (HT), or high blood pressure is one of the most common and main causes in cardiovascular diseases, which is also related to a series of detrimental diseases in humans. Deficiencies in effective treatment in HT are often associated with a series of diseases including multi-infarct dementia, amputation, and renal failure. Therefore, identifying anti-hypertension peptides has the vital realistic significance. Although many bioactive peptides have been developed to reduce blood pressure, they are time-consuming and laborious. In views of the obstacles of the intrinsic methods in antihypertensive peptide (AHTP) classification, computational methods are suggested as a supplement to identify AHTPs. In this study, we develop a comprehensive feature representation algorithm based on pretrained model and convolutional neural network and apply the deep ensemble model to construct the prediction model. The new predictor is used to identify AHTPs in benchmark and independent datasets. It has been shown in the independent test set that the performance is better than the recent methods. Comparative results indicate that our model can shed some light on hypertension therapy and gains more insights of classifying AHTPs. The implements and codes can be found in https://github.com/yuanying566/AHPred-DE.
Topics: Algorithms; Antihypertensive Agents; Humans; Neural Networks, Computer; Peptides; Proteins
PubMed: 33760739
DOI: 10.1109/TCBB.2021.3068381 -
Maturitas Jan 2021Telemedicine is a timely solution for the restrictions that COVID-19 social distancing places upon conventional modalities of healthcare provision. Geriatric populations...
BACKGROUND
Telemedicine is a timely solution for the restrictions that COVID-19 social distancing places upon conventional modalities of healthcare provision. Geriatric populations affected by dementia require greater access to healthcare services, particularly in rural areas. As such, the aim of this systematic review is to examine the impact of telemedicine on health outcomes in elderly individuals with dementia living in rural areas.
METHODS
A systematic review was completed using Ovid Medline, Web of Science and ACM Digital Libraries. The keywords for the selection of articles were: (telemedicine OR Telehealth) AND (Rural) AND (Age* OR Eld*) AND (Dementia) and (Telemedicine) AND (Rural Health OR Rural Population OR Hospitals, Rural OR Rural Health Services) AND (Aged OR Aging) AND (Dementia OR Multi-Infarct Dementia OR Vascular Dementia OR Frontotemporal Dementia). Among the 94 articles identified, 79 (84.0 %) were screened, 58 (61.7 %) were assessed and 12 (12.8 %) were included.
RESULTS
The studies had diverse populations. Two were conducted in Australia, five in Canada, one in Korea, and four in the United States of America. The studies used a variety of cognitive tests and reported mixed results regarding the differences in patient performance when assessed in-person as compared to telemedicine consultation. Overall, both patients and physicians reported satisfaction with telemedicine; however, there were mixed results regarding the reliability of cognitive tests and the infrastructure required. Convenience, satisfaction, comfort and recommending telemedicine were reported to be high in the telemedicine group and physicians reported they would use telemedicine again.
CONCLUSION
The testing conditions and the accessibility of telemedicine yield inconclusive results as to whether telemedicine can improve the management of dementia in geriatric individuals.
Topics: Aged; Attitude of Health Personnel; COVID-19; Dementia; Health Services Accessibility; Humans; Neuropsychological Tests; Patient Satisfaction; Reproducibility of Results; Rural Population; SARS-CoV-2; Telemedicine
PubMed: 33308615
DOI: 10.1016/j.maturitas.2020.09.001 -
BMJ Case Reports Dec 2020Marchiafava-Bignami disease (MBD) is a rare, toxic demyelinating disorder of the central nervous system associated with chronic alcoholism and malnutrition. The clinical...
Marchiafava-Bignami disease (MBD) is a rare, toxic demyelinating disorder of the central nervous system associated with chronic alcoholism and malnutrition. The clinical presentation is varied and non-specific, including symptoms of acute dementia, impaired consciousness, dysarthria, hemiparesis, pyramidal tract signs, seizure activity, ataxia and signs of interhemispheric disconnection. The differential diagnosis of MBD may include Wernicke's encephalopathy, multiple sclerosis, encephalitis, infectious or paraneoplastic leucoencephalopathy, infarction, Alzheimer's disease, multi-infarct dementia and frontotemporal lobar degeneration (Pick) disease. The diagnosis of MBD is dependent on MRI findings of hyperintensity of the corpus callosum on T2 and fluid-attenuated inversion recovery T2 sequences, with or without extracallosal lesions. The use of MRI in diagnosis has allowed for early initiation of treatment with parenteral thiamine, and improved the prognosis of MBD from frequently fatal to a mortality of less than 8%. Administration of thiamine within 14 days of symptom onset has demonstrated statistically better outcomes over delayed treatment. We present a case report of MBD diagnosed in a 72-year-old woman who presented with ataxia and slurred speech, in an effort to highlight the importance of obtaining MRI in patients presenting with behavioural disturbance and neurological findings, as well as discuss the relationship between thiamine supplementation and demyelinating diseases in the central nervous system.
Topics: Aged; Alcoholism; Corpus Callosum; Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Malnutrition; Marchiafava-Bignami Disease; Thiamine; Thiamine Deficiency
PubMed: 33303506
DOI: 10.1136/bcr-2020-238187 -
European Review For Medical and... Sep 2020Vascular dementia is the second-most cause of dementia, characterized by cerebral infarcts, white matter lesions, myelin loss and often amyloid angiopathy. Hence,... (Review)
Review
Vascular dementia is the second-most cause of dementia, characterized by cerebral infarcts, white matter lesions, myelin loss and often amyloid angiopathy. Hence, vascular damage is a critical cause of neuronal loss and synaptic disintegration. Abnormal neuroinflammation, autophagy and apoptosis are the prerequisite factors for endothelial and neuronal cell damage. This leads to the onset and progression of cerebrovascular disorders and cognitive dysfunction. The innate immune cells, pattern recognition receptors, Toll-like receptor-4 and related inflammatory mechanisms disrupt cerebrovascular integrity via glial activation and increased pro-inflammatory interleukins and TNFα. Inflammasome polymorphisms and multi-faceted neuro-immune interactions further integrate systemic and central inflammatory pathways, which induce vascular tissue injury and neurodegeneration. Specifically, chronic cerebral hypoperfusion disrupts the self-cannibalization mechanism of autophagy via altered expression of autophagy-specific proteins, Beclin-1, LC3 and P62. The deregulated autophagy pathway causes neuronal loss, hippocampal shrinkage, and ultimate loss in synaptic plasticity. The vascular dementia models typically exhibit downregulated anti-apoptotic Bcl-2 and upregulated pro-apoptotic Bax, cleaved caspase-3, and cleaved-PARP levels in the brain, for which modulated p38 MAPK and JNK phosphorylation pathways play a vital role. Endoplasmic stress-induced apoptosis, calcium overload and glutamate excitotoxicity in combination with ASK1-MAPK signaling mechanism also contribute to the cerebrovascular pathology. Vascular injury reduces neurological scores and increases the infarct volume, DNA damage and neuronal apoptosis in ischemia/reperfusion injury. Additionally, synergistic and additive interactions between inflammasome, autophagy and apoptotic signaling pathways augment symptoms of vascular neurodegeneration. Overall, the current review enlightens the key risk factors and underlying mechanism triggering vascular dementia. The review additionally informs the challenges associated while treating vascular dysfunction, and highlights the need for targeted drugs for reducing cerebrovascular damage.
Topics: Animals; Apoptosis; Dementia, Vascular; Humans; Inflammation
PubMed: 33015803
DOI: 10.26355/eurrev_202009_23048 -
Zeitschrift Fur Gerontologie Und... Nov 2020Vascular dementias (VD, due to the various expressions of VD the plural form is used) are the second most common form of dementia after Alzheimer's dementia. These...
Vascular dementias (VD, due to the various expressions of VD the plural form is used) are the second most common form of dementia after Alzheimer's dementia. These dementias play an important role especially in geriatric patients. They can occur due to acute events (e.g. stroke) and due to slowly progressive cerebrovascular damage. This article focuses on VD due to cortical and strategic infarcts, microangiopathic infarcts with lacunae as well as intracerebral bleeding. In addition to the clinical description and radiological findings, a special focus is on education, prevention and rehabilitation aspects.
Topics: Aged; Alzheimer Disease; Dementia, Vascular; Educational Status; Humans; Stroke
PubMed: 32975634
DOI: 10.1007/s00391-020-01786-3 -
Experimental and Therapeutic Medicine Nov 2020Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's...
Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's disease. While only a limited range of drugs is available, the incidence of MID is increasing year on year. The present study aimed to investigate the effect and underlying mechanisms of a combination of ginsenosides and astragalosides (CGA) on cognitive decline in rats with MID. A rat model of MID was established using micro-thromboembolism, and the behavioral changes in the rats were evaluated using the Morris water maze and open field tests at 60 days post-CGA intervention. The pathological morphology of the hippocampal CA1 area was observed using hematoxylin and eosin staining. The contents of ATP, ADP and AMP were determined using high-performance liquid chromatography. Mitochondrial swelling and changes in the membrane potential in the hippocampus were detected using flow cytometry, and the changes in insulin, glutamate and γ-aminobutyric acid (GABA) content were detected using ELISA. Additionally, the expression of PI3K and AKT proteins was detected using western blot analysis. In a rat model of MID, CGA shortened the escape latency, increased the frequency of platform crossing, improved the disordered vertebral cell arrangement and reduced the cell number in the hippocampal CA1 area. CGA also reduced the degree of mitochondrial swelling, increased the mitochondrial membrane potential, and elevated the energy load and ATP content in the brain of rats with MID. Furthermore, CGA increased the insulin content and upregulated the expression of PI3K and AKT in the brain of rats with MID. In addition, in the rat model of MID, CGA also enhanced the movement time and the frequency of standing, and decreased the concentration of glutamate and GABA in the brain tissue. Amelioration of the cognitive decline in rats with MID by CGA was associated with its regulatory effect on the PI3K/AKT signaling pathway and neurotransmitter systems.
PubMed: 32963600
DOI: 10.3892/etm.2020.9198 -
Neurophysiologie Clinique = Clinical... Jul 2020The aim of the present study was to identify neurophysiologic markers to differentiate between Alzheimer dementia (AD), Vascular dementia (VaD), and Parkinson's disease...
BACKGROUND
The aim of the present study was to identify neurophysiologic markers to differentiate between Alzheimer dementia (AD), Vascular dementia (VaD), and Parkinson's disease dementia (PDD), and to examine their relationship to levels of transforming growth factor β1 (TGFβ1).
METHODS
The study included 15 patients with each type of dementia (AD, VaD, PDD) and 25 control subjects. Dementia patients were diagnosed according to the DiagnosticandStatisticalManualofMentalDisorders4thedition-revised(DSM-IV-R). Modified Mini Mental State Examination (MMMSE), motor cortex excitability including resting and active motor thresholds (rMT, aMT), input-output (I/O) curve, contralateral and ipsilateral silent periods (cSP, iSP), short-interval intracortical inhibition (SICI) at 1,2 and 4ms, and serum levels of TGFβ1 were examined.
RESULTS
There were no significant differences between groups with regards to age, sex, education or socioeconomic level. There was significant neuronal hyperexcitability in the form of reduced rMT and aMT and a shallower I/O curve in all three groups of dementia compared with the control group. The durations of cSP and iSP were longer in AD and PDD groups compared with the control group, whereas there were no significant differences in VaD. SICI was less effective in the three dementia groups than in the control group at intervals of 4ms. Serum levels of TGFβ1 were significantly elevated in all dementia groups in comparison with the control group. There was a significant negative correlation between serum level of TGFβ1 and cSP, iSP, and SICI across all patients and a significant negative correlation between serum level of TGFβ1 and iSP duration in AD.
CONCLUSION
Although motor thresholds were reduced in all patients, measures of SICI, cSP and iSP could distinguish between dementia groups. Serum level of TGFβ1 negatively correlated with iSP specifically in the AD group. This suggests that levels of TGFβ1 may relate to GABAergic dysfunction in dementia.
Topics: Aged; Alzheimer Disease; Biomarkers; Cortical Excitability; Dementia; Dementia, Vascular; Evoked Potentials, Motor; Female; Humans; Male; Middle Aged; Motor Cortex; Parkinson Disease; Transcranial Magnetic Stimulation; Transforming Growth Factor beta1
PubMed: 32591186
DOI: 10.1016/j.neucli.2020.05.001 -
Nature Communications Jan 2020The clinical diagnosis of vascular dementia (VaD) is based on imaging criteria, and specific biochemical markers are not available. Here, we investigated the potential...
The clinical diagnosis of vascular dementia (VaD) is based on imaging criteria, and specific biochemical markers are not available. Here, we investigated the potential of cerebrospinal fluid (CSF) lipocalin 2 (LCN2), a secreted glycoprotein that has been suggested as mediating neuronal damage in vascular brain injuries. The study included four independent cohorts with a total n = 472 samples. LCN2 was significantly elevated in VaD compared to controls, Alzheimer's disease (AD), other neurodegenerative dementias, and cognitively unimpaired patients with cerebrovascular disease. LCN2 discriminated VaD from AD without coexisting VaD with high accuracy. The main findings were consistent over all cohorts. Neuropathology disclosed a high percentage of macrophages linked to subacute infarcts, reactive astrocytes, and damaged blood vessels in multi-infarct dementia when compared to AD. We conclude that CSF LCN2 is a promising candidate biochemical marker in the differential diagnosis of VaD and neurodegenerative dementias.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Cerebrovascular Disorders; Dementia, Vascular; Diagnosis, Differential; Female; Humans; Lipocalin-2; Male; Middle Aged
PubMed: 32001681
DOI: 10.1038/s41467-020-14373-2