scholarly journals Nanotargeting of Drug(s) for Delaying Dementia: Relevance of Covid-19 Impact on Dementia

2020 ◽  
Vol 35 ◽  
pp. 153331752097676
Author(s):  
Joseph S. D’Arrigo
Keyword(s):  
Risk Factors ◽  
Memory Impairment ◽  
Late Onset ◽  
Scavenger Receptors ◽  
Type I ◽  
Human Coronavirus ◽  
Memory Decline ◽  
Class B ◽  
Lipid Nanocarriers ◽  
Late Onset Dementia

By incorporating appropriate drug(s) into lipid (biobased) nanocarriers, one obtains a combination therapeutic for dementia treatment that targets certain cell-surface scavenger receptors (mainly class B type I, or “SR-BI”) and thereby crosses the blood-brain barrier. The cardiovascular risk factors for dementia trigger widespread inflammation -- which lead to neurodegeneration, gradual cognitive/memory decline, and eventually (late-onset) dementia. Accordingly, one useful strategy to delay dementia could be based upon nanotargeting drug(s), using lipid nanocarriers, toward a major receptor class responsible for inflammation-associated (cytokine-mediated) cell signaling events. At the same time, the immune response and excessive inflammation, commonly observed in the very recent human coronavirus (COVID-19) pandemic, may accelerate the progression of brain inflammatory neurodegeneration—which increases the probability of post-infection memory impairment and accelerating progression of Alzheimer’s disease. Hence, the proposed multitasking combination therapeutic, using a (biobased) lipid nanocarrier, may also display greater effectiveness at different stages of dementia.

scholarly journals Biomimetic Nanocarrier Targeting Drug(s) to Upstream-Receptor Mechanisms in Dementia: Focusing on Linking Pathogenic Cascades

Biomimetics ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 11 ◽  
Author(s):  
Joseph S. D’Arrigo
Keyword(s):  
Late Onset ◽  
Biomedical Application ◽  
High Density Lipoproteins ◽  
Scavenger Receptors ◽  
Cubic Phase ◽  
Type I ◽  
Amyloid A ◽  
Medical Disorders ◽  
Class B ◽  
Late Onset Dementia

Past published studies have already documented that, subsequent to the intravenous injection of colloidal lipid nanocarriers, apolipoprotein (apo)A-I is adsorbed from the blood onto the nanoparticle surface. The adsorbed apoA-I mediates the interaction of the nanoparticle with scavenger receptors on the blood–brain barrier (BBB), followed by receptor-mediated endocytosis and subsequent transcytosis across the BBB. By incorporating the appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the BBB. Documented similarities in lipid composition between naturally occurring high-density lipoproteins (HDL) and the artificial biomimetic (nanoemulsion) nanocarrier particles can partially simulate or mimic the known heterogeneity (i.e., subpopulations or subspecies) of HDL particles. Such biomedical application of colloidal drug-nanocarriers can potentially be extended to the treatment of complex medical disorders like dementia. The risk factors for dementia trigger widespread inflammation and oxidative stress; these two processes involve pathophysiological cascades which lead to neuronal Ca2+ increase, neurodegeneration, gradual cognitive/memory decline, and eventually (late-onset) dementia. In particular, more recent research indicates that chronic inflammatory stimulus in the gut may induce (e.g., via serum amyloid A (SAA)) the release of proinflammatory cytokines. Hence, an effective preventive and therapeutic strategy could be based upon drug targeting toward a major SAA receptor responsible for the SAA-mediated cell signaling events leading to cognitive decline and eventually Alzheimer’s disease or (late-onset) dementia.

Family with 22-derived marker chromosome and late-onset dementia of the Alzheimer type: I. Application of a new model for estimation of the risk of disease associated with the marker

1991 ◽  
Vol 39 (3) ◽  
pp. 307-313 ◽  
Author(s):  
Maire E. Percy ◽  
Vjerica D. Markovic ◽  
Donald R. Crapper McLachlan ◽  
Joseph M. Berg ◽  
Jocelyn T. Hummel ◽  
...  
Keyword(s):  
Late Onset ◽  
Marker Chromosome ◽  
Type I ◽  
Alzheimer Type ◽  
New Model ◽  
Risk Of Disease ◽  
Late Onset Dementia

scholarly journals Suicidal Ideations and Behavior in Patients With Young and Late Onset Dementia

2021 ◽  
Vol 12 ◽  
Author(s):  
Marion Ortner ◽  
Lina Riedl ◽  
Ralf J. Jox ◽  
Julia Hartmann ◽  
Carola Roßmeier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Suicidal Ideation ◽  
Suicidal Behavior ◽  
Late Onset ◽  
Physical Symptoms ◽  
Advanced Dementia ◽  
Death Wishes ◽  
And Behavior ◽  
Late Onset Dementia

Background and Objectives: Data on suicidal ideation, behavior and the risk factors in patients with dementia is scarce. To evaluate the prevalence of death wishes, suicidal ideation, and suicidal behavior of young (YOD) and late onset dementia (LOD) and to identify risk factors for suicidal ideation and behavior.Methods: We interviewed 157 family caregivers of patients with advanced dementia using questions from the Columbia-Suicide Severity Rating Scale to gather information about suicidal ideation and behavior before the onset of symptoms of dementia, after the onset of dementia and within 30 days prior to the interview. At the time of the interview, we also assessed disease severity, cognitive function, and other psychological, behavioral and physical symptoms of the patients as well as the caregivers' psychological well-being.Results: Forty four (28%) of the patients expressed suicidal ideation or behavior at some time after the onset of symptoms, and 14 (9%) of these within the month prior to the assessment. Two patients had attempted suicide after the onset of dementia. There were no statistically significant differences between patients with and without suicidal ideations or behavior with regards to demographics or age at onset of dementia. In patients with advanced dementia, Alzheimer's disease (rather than frontotemporal lobar degeneration), better cognitive function, more severe psychological, behavioral, and physical symptoms, and a reduced quality of life were associated with the expression of suicidal ideation.Conclusions: According to caregivers' reports, majority of patients with dementia did not express suicidal ideation or show suicidal behavior. Patients who expressed suicidal ideation during early stages of dementia often stopped expressing them in advanced stages. It remains unclear if this was due to reduced communication abilities, a reduction of disease awareness, and/ or an adjustment to their situation.

scholarly journals Lifestyle risk Factors for early versus late onset dementia: A systematic review and meta-analysis

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
N Berselli ◽  
G Adani ◽  
T Filippini ◽  
M Vinceti
Keyword(s):  
Risk Factors ◽  
Brain Injuries ◽  
Age Of Onset ◽  
Late Onset ◽  
Meta Analysis ◽  
Lifestyle Risk Factors ◽  
Modifiable Factors ◽  
Lifestyle Risk ◽  
The Impact ◽  
Late Onset Dementia

Abstract Background Dementia is a widely prevalent and growing condition, affecting nearly 10% of people aged 60 years and older. It is a leading cause of disability entailing important economic and social costs for the population, so much so that it has been defined as a “global public health priority' from WHO in 2016. Dementia can be divided into two forms according to age of onset of the first symptoms: Early Onset Dementia (EOD - < 65 years) and Late Onset Dementia (LOD, ≥ 65 years). The differences between the two forms, and if they could be considered as separate diseases, are still not well understood. The aim of this meta-analysis was to determine if environmental-lifestyle risk factors of dementia may differ between EOD and LOD. Methods Literature databases were searched to June 2020, to retrieve studies assessing the impact of modifiable factors in patients who had developed the first symptoms of dementia before (for EOD) or after (for LOD) 65 years. Data were then meta-analysed in order to understand the overall impact of the single factors on EOD and LOD separately. Results The results show different effects for some risk factors as alcohol consumption (OR 2.8, 95%CI: 2.2-3.4 for EOD and OR 1.2, 95%CI: 0.9-1.5 for LOD) and brain injuries (OR 1.4, 95%CI: 1.2-1.6 for EOD, and OR 1, 95%CI: 0.6-1.4 for LOD), which appear to have more impact on EOD compared with LOD. No association with smoking for both forms of dementia emerged. The other factors considered, such as low educational attainment, socio-economic status, closeness of magnetic field, appear to have similar impact on the two forms of dementia. Conclusions These results suggest that there may be a difference, in terms of modifiable risk factors, between the two forms of dementia, even if more research is needed on this issue. Key messages There may be different risk factors determining EOD versus LOD onset. By modifying some environmental and lifestyle factors we could delay or prevent the onset of dementia.

scholarly journals Effective interventions for potentially modifiable risk factors for late-onset dementia: a costs and cost-effectiveness modelling study

2020 ◽  
Vol 1 (1) ◽  
pp. e13-e20 ◽  
Author(s):  
Naaheed Mukadam ◽  
Robert Anderson ◽  
Martin Knapp ◽  
Raphael Wittenberg ◽  
Maria Karagiannidou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cost Effectiveness ◽  
Late Onset ◽  
Modifiable Risk Factors ◽  
Effective Interventions ◽  
Late Onset Dementia ◽  
Modelling Study

scholarly journals Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells

2018 ◽  
Vol 217 (6) ◽  
pp. 2103-2119 ◽  
Author(s):  
Fengyi Gao ◽  
Guoping Li ◽  
Chao Liu ◽  
Hui Gao ◽  
Hao Wang ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Late Onset ◽  
Scavenger Receptor ◽  
Serum Testosterone ◽  
Autophagic Flux ◽  
Type I ◽  
Cholesterol Uptake ◽  
Steroidogenic Cell ◽  
Class B ◽  
Testosterone Synthesis

Testosterone is indispensable for sexual development and maintaining male characteristics, and deficiency of this hormone results in primary or late-onset hypogonadism (LOH). Testosterone is primarily produced in Leydig cells, where autophagy has been reported to be extremely active. However, the functional role of autophagy in testosterone synthesis remains unknown. In this study, we show that steroidogenic cell–specific disruption of autophagy influenced the sexual behavior of aging male mice because of a reduction in serum testosterone, which is similar to the symptoms of LOH. The decline in testosterone was caused mainly by a defect in cholesterol uptake in autophagy-deficient Leydig cells. Further studies revealed that once autophagic flux was disrupted, Na+/H+ exchanger regulatory factor 2 (NHERF2) accumulated in Leydig cells, resulting in the down-regulation of scavenger receptor class B, type I (SR-BI) and eventually leading to insufficient cholesterol supply. Collectively, these results reveal that autophagy promotes cholesterol uptake into Leydig cells by eliminating NHERF2, suggesting that dysfunction of autophagy might be causal in the loss of testosterone production in some patients.

scholarly journals Cardiovascular complications in patients with cancer: focus on anthracycline-induced cardiotoxicity

2021 ◽  
Vol 20 (2) ◽  
Author(s):  
I. T. Murkamilov ◽  
K. A. Aitbaev ◽  
V. V. Fomin ◽  
I. O. Kudaibergenova ◽  
F. A. Yusupov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Late Onset ◽  
Beta Blockers ◽  
Myocardial Dysfunction ◽  
Myocardial Damage ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Type I ◽  
Patients With Cancer ◽  
Cardioprotective Effects

The article describes prevalence and risk factors of cardiovascular in patients with cancer. The problems of anthracycline-induced cardiotoxicity, the deleterious effects of doxorubicin on the heart, as well as the cardioprotective effects of beta-blockers and agents acting on the renin-angiotensin-aldosterone system pathway are discussed. By cardiotoxicity is implied the development of various adverse cardiovascular events against the background of drug therapy for cancer patients. Depending on the severity of myocardial damage, there are type I (anthracycline-mediated cardiotoxicity, myocardial damage is irreversible) and type II (trastuzumab-mediated cardiotoxicity, myocardial dysfunction is reversible) cardiotoxicity. Anthracycline-induced cardiotoxicity, in turn, is divided into acute, early-onset chronic and late-onset chronic. At the same time, the main mechanisms of anthracycline cytotoxicity in relation to healthy cardiomyocytes are stimulation of intracellular oxidative stress, a decrease in reduced glutathione concentration, inhibition of cell redox potential, and a change in iron metabolism. The article discusses in detail the risk factors (age, hypertension, diabetes, asymptomatic left ventricular dysfunction, documented cardiovascular diseases, heart failure, etc.), as well as the mechanisms and treatment of anthracycline-mediated cardiotoxicity.

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