scholarly journals Fully Bayesian longitudinal unsupervised learning for the assessment and visualization of AD heterogeneity and progression

2019 ◽  
Author(s):  
Konstantinos Poulakis ◽  
Daniel Ferreira ◽  
Joana B. Pereira ◽  
Örjan Smedby ◽  
Prashanthi Vemuri ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Brain Atrophy ◽  
Amyloid Β ◽  
Control Group ◽  
Longitudinal Assessment ◽  
Group 4 ◽  
Disease Staging ◽  
Hippocampal Sparing ◽  
Brain Data ◽  
Fully Bayesian

AbstractTau pathology and regional brain atrophy are the closest correlate of cognitive decline in Alzheimer’s disease (AD). Understanding heterogeneity and longitudinal progression of brain atrophy during the disease course will play a key role in understanding AD pathogenesis. We propose a framework for longitudinal clustering that: 1) incorporates whole brain data, 2) leverages unequal visits per individual, 3) compares clusters with a control group, 4) allows to study confounding effects, 5) provides clusters visualization, 6) measures clustering uncertainty, all these simultaneously. We used amyloid-β positive AD and negative healthy subjects, three longitudinal sMRI scans (cortical thickness and subcortical volume) over two years. We found 3 distinct longitudinal AD brain atrophy patterns: a typical diffuse pattern (n=34, 47.2%), and 2 atypical patterns: Minimal atrophy (n=23 31.9%) and Hippocampal sparing (n=9, 12.5%). We also identified outliers (n=3, 4.2%) and observations with uncertain classification (n=3, 4.2%). The clusters differed not only in regional distributions of atrophy at baseline, but also longitudinal atrophy progression, age at AD onset, and cognitive decline. A framework for the longitudinal assessment of variability in cohorts with several neuroimaging measures was successfully developed. We believe this framework may aid in disentangling distinct subtypes of AD from disease staging.

Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations

2021 ◽  
pp. 1-9
Author(s):  
Gihwan Byeon ◽  
Min Soo Byun ◽  
Dahyun Yi ◽  
Jun Ho Lee ◽  
So Yeon Jeon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Older Adults ◽  
Cognitive Decline ◽  
Brain Atrophy ◽  
Homocysteine Level ◽  
Cognitive Impairments ◽  
Interactive Effect ◽  
Brain Mri ◽  
Amyloid Β ◽  
Serum Homocysteine

Background: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM. Objective: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments. Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI. Results: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer’s disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD. Conclusion: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.

scholarly journals Gestational Stress Augments Postpartum β-Amyloid Pathology and Cognitive Decline in a Mouse Model of Alzheimer’s Disease

2018 ◽  
Vol 29 (9) ◽  
pp. 3712-3724 ◽  
Author(s):  
Zahra Jafari ◽  
Jogender Mehla ◽  
Bryan E Kolb ◽  
Majid H Mohajerani
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cognitive Decline ◽  
Noise Exposure ◽  
Amyloid Β ◽  
Control Group ◽  
Plaque Size ◽  
Model Of Alzheimer’S Disease ◽  
Gestational Stress

Abstract Besides well-known risk factors for Alzheimer’s disease (AD), stress, and in particular noise stress (NS), is a lifestyle risk factor common today. It is known that females are at a significantly greater risk of developing AD than males, and given that stress is a common adversity in females during pregnancy, we hypothesized that gestational noise exposure could exacerbate the postpartum development of the AD-like neuropathological changes during the life span. Pregnant APPNL-G-F/NL-G-F mice were randomly assigned to either the stress condition or control group. The stress group was exposed to the NS on gestational days 12–16, which resulted in a markedly higher hypothalamic–pituitary–adrenal (HPA) axis responsivity during the postpartum stage. Higher amyloid-β (Aβ) deposition and larger Aβ plaque size in the olfactory area were the early onset impacts of the gestational stress (GS) seen at the age of 4 months. This pattern of increased Aβ aggregation and larger plaque size were observed in various brain areas involved in both AD and stress regulation, especially in limbic structures, at the age of 6 months. The GS also produced anxiety-like behavior, deficits in learning and memory, and impaired motor coordination. The findings suggest that environmental stresses during pregnancy pose a potential risk factor in accelerating postpartum cognitive decline and AD-like neuropathological changes in the dams (mothers) later in life.

Antimicrobial Effect of 940 nm Diode Laser based on Photolysis of Hydrogen Peroxide in the Treatment of Periodontal Disease

2018 ◽  
Vol 69 (8) ◽  
pp. 2081-2088 ◽  
Author(s):  
Alin Alexandru Odor ◽  
Edwin Sever Bechir ◽  
Deborah Violant ◽  
Victoria Badea
Keyword(s):  
Hydrogen Peroxide ◽  
Laser Therapy ◽  
Diode Laser ◽  
Antimicrobial Effect ◽  
The Other ◽  
Control Group ◽  
Group 4 ◽  
Periodontal Bacteria ◽  
Severe Periodontitis ◽  
Before And After

Moderate and severe periodontitis represents a challenge in the non-surgical periodontal therapy. Due to the lack of evidence regarding the antimicrobial effectiveness of 940 nm diode laser in periodontal treatment, this study aimed to evaluate the antimicrobial effect of hydrogen peroxide (H2O2) photolysis performed with 940 nm diode laser in the treatment of moderate and severe periodontitis. Twenty-five patients with 100 teeth were selected for this pilot study. The test teeth were randomly assigned to one of the four treatment groups: Group 1: scaling and root planning (SRP) (control group); and the following experimental groups: Group 2: H2O2; Group 3: 940 nm diode laser therapy; Group 4: 940 nm diode laser therapy and H2O2. Clinical examinations, like probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were performed before and after the treatment. The microbiological evaluation, effectuated before and after the treatment, included nine periodontal bacteria species and investigated by means of real-time PCR assay. The clinical and bacterial differences in the tested groups, was assessed between control group and the other three experimental groups, as well as between the experimental groups. The total bacteria load was reduced for all four studied groups. Group 4 (diode laser + H2O2) showed significant bacterial reduction of the major periodontal bacteria like Pg., Tf., Td., Pi., Pm., Fn (p[0.001) than the other 3 groups (p]0.001). Also the periodontal clinical parameters, like PD, CAL and BOP showed a significant reduction after the photolysis of H2O2 with the 940 nm diode laser (p[0.001). Differences between tested groups showed a significant beneficial results in regard to Group 4.It is suggested that the photoactivation of H2O2 with the 940 nm diode laser can be used successfully in adjunctive to the non-surgical periodontal treatment as a bactericidal tool.

Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia

2018 ◽  
Vol 15 (4) ◽  
pp. 386-398 ◽  
Author(s):  
Fabricio Ferreira de Oliveira ◽  
Elizabeth Suchi Chen ◽  
Marilia Cardoso Smith ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Cognitive Decline ◽  
Enzyme Inhibitors ◽  
Late Onset ◽  
Amyloid Β ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Alzheimer’S Disease Dementia

Background: While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer’s disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification. Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis. Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 – C (44.6% heterozygotes) and 0.345 for rs4291 – T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 – T and rs4291 – A, or for APOE4- carriers of rs1800764 – T or rs4291 – T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis. Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes.

The Effects of the "XGTQ" Medicine in Treating Cirrhosis in Wistar Rats

2020 ◽  
Vol 06 ◽  
Author(s):  
Ngan Nguyen Hoang ◽  
Thang Duong Minh ◽  
Tuan Anh Hoang ◽  
Son Le Ngoc Bich ◽  
Duong Nguyen Huu ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Reference Group ◽  
Control Group ◽  
Plain Water ◽  
Group 4 ◽  
White Rats ◽  
Collagen Accumulation ◽  
Activity Of Enzymes ◽  
Group 3 ◽  
Group 1

Objectives: Evaluate the effects of "XGTQ" in the treatment of cirrhosis induced by Carbon tetrachloride (CCL4) in combination with alcohol and high-fat diet on Wistar rats. Materials and methods: Cirrhosis on white rats was induced by subcutaneously injecting CC14 at an initial dose of 5,0ml/kg, followed by 1,2ml/kg once a week in 10 weeks. Then, fed with synthetic food, added 20% fat, and 0.05% cholesterol and iron oxalate. Rats were administered every day with plain water and 1 day with water mixed with 30% ethanol. The rats were randomly divided into 5 groups and given distilled water (group 1 and 2 or control group), silymarin (group 3 or reference group) or the "XGTQ" drug extract (group 4, 5) for 4 weeks. Collected blood for biochemical test and liver were dissected to evaluate weight, morphology and quantified 4-hydroxyproline to evaluate fibrosis and collagen accumulation. Results: In cirrhotic wistar rats, "XGTQ" drug at 19.6 g/kg/24h and 58.8 g/kg/24h showed the ability of reducing the activity of enzymes AST, ALT in the blood (p<0.01), increasing plasma albumin and decreasing prothrobin time (p<.05); improving physical condition, macroscopic and microscopic images of H&E-stained liver; decreasing the concentration of hydroxyproline in the liver and reducing the level of cirrhosis on the masson-stained templates. The effects of "XGTQ" increased with the dose, and was equivalent to silymarin at the dose of 70 mg/kg/24h. Conclusion: The extract of "XGTQ" drug is effective in treating cirrhosis in Wistar rats.

scholarly journals Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandra Rajewska-Rager ◽  
Monika Dmitrzak-Weglarz ◽  
Pawel Kapelski ◽  
Natalia Lepczynska ◽  
Joanna Pawlak ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Calcium Binding ◽  
Clinical Symptoms ◽  
Small Sample Size ◽  
Serum Levels ◽  
Small Sample ◽  
Drop Out ◽  
Control Group ◽  
Longitudinal Assessment ◽  
Depressed Group

AbstractMood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

scholarly journals 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 190
Author(s):  
Nikita Martens ◽  
Melissa Schepers ◽  
Na Zhan ◽  
Frank Leijten ◽  
Gardi Voortman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Inflammatory Marker ◽  
Amyloid Β ◽  
Liver Fat ◽  
Gas Chromatography Mass Spectrometry ◽  
Memory Decline ◽  
Plaque Load

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

scholarly journals Evaluation of Three Formulations of Essential Oils in Broiler Chickens under Cyclic Heat Stress

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1084
Author(s):  
Jared Ruff ◽  
Guillermo Tellez ◽  
Aaron J. Forga ◽  
Roberto Señas-Cuesta ◽  
Christine N. Vuong ◽  
...  
Keyword(s):  
Heat Stress ◽  
Essential Oils ◽  
Broiler Chickens ◽  
Bone Mineralization ◽  
Body Core Temperature ◽  
Control Group ◽  
Group 4 ◽  
Body Core ◽  
Cyclic Heat ◽  
Group 2

The objective of the present research was to assess the dietary supplementation of three formulations of essential oils (EO) in chickens under heat stress (HS). Day-of-hatch Cobb 500 chicks (n = 500) were randomly distributed into four groups: 1. HS control + control diets; 2. HS + control diets supplemented with 37 ppm EO of Lippia origanoides (LO); 3. HS + control diets supplemented with 45 ppm LO + 45 ppm EO of Rosmarinus officinalis (RO) + 300 ppm red beetroot; 4. HS + 45 ppm LO + 45 ppm RO + 300 ppm natural betaine. Chickens that received the EO showed significant (p < 0.05) improvement on BW, BWG, FI, and FCR compared to control HS chickens. Average body core temperature in group 3 and group 4 was significantly (p < 0.05) reduced compared with the HS control group and group 2. Experimental groups showed a significant reduction in FITC-d at 42 days, a significant increase in SOD at both days but a significant reduction of IFN-γ and IgA compared with HS control (p < 0.05). Bone mineralization was significantly improved by EO treatments (p < 0.05). Together these data suggest that supplemental dietary EO may reduce the harmful effects of HS.

scholarly journals Clinical Outcome and Histological Findings After Induced Leakage of PMMA Loaded With Methotrexate and Cisplatin During Vertebroplasty: Experimental Model in Pigs

2021 ◽  
pp. 219256822199480
Author(s):  
Alvaro Silva González ◽  
Rafael Llombart-Blanco ◽  
Marcela Gallegos Angulo ◽  
Carlos Villas Tomé ◽  
Matías Alfonso Olmos-García
Keyword(s):  
Spinal Cord ◽  
Experimental Model ◽  
Motor Impairment ◽  
Clinical Results ◽  
Control Group ◽  
Safe Procedure ◽  
Group 4 ◽  
Cement Leak ◽  
Group 2 ◽  
Histological Results

Study Design: Animal experimental model. Objective: To study the clinical behavior and histological changes in the spinal cord, nerve roots and perivertebral muscles of the spine after induced leakage of polymethylmethacrylate (PMMA) loaded with antiblastic drugs during vertebroplasty in an animal model of pigs. Methods: We performed vertebroplasty on 25 pigs. The animals were divided into 3 groups: vertebroplasty with PMMA alone (control group), vertebroplasty with PMMA loaded with methotrexate (MTX) and vertebroplasty with PMMA loaded with cisplatin (CYS). At 2 vertebral levels, epidural and prevertebral, massive cement leaks were induced. Animals were evaluated daily. Two weeks later, the pigs were sacrificed, and the tissues that came in contact with the cement were analyzed. Results: The clinical results for each of the groups were reported. The control group had no clinical alterations. In the MTX group, 2 pigs died before 1 week due to pneumonitis. In the CYS group, 4 animals had motor impairment, and 3 of the 4 had paraplegia. The histological results were as follows: the control and MTX groups showed synovial metaplasia, inflammatory reaction, crystal deposits, and giant cell reaction in the dura mater and muscle and all the animals in the CYS group had spinal cord and muscular necrosis. Conclusions: Massive cement leak after vertebroplasty with PMMA loaded with cisplatin is extremely toxic to the spinal cord and muscles around the spine. Therefore, its use cannot be recommended for the treatment of vertebral metastases. Using PMMA loaded with methotrexate seems to be a safe procedure, but further research is needed.

scholarly journals 332 - Electroconvulsive therapy in older adults with major depression was not associated with cognitive decline during a 15-year follow-up

2020 ◽  
Vol 32 (S1) ◽  
pp. 91-91
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Major Depression ◽  
Cognitive Decline ◽  
Electroconvulsive Therapy ◽  
Antidepressant Treatment ◽  
Community Sample ◽  
Control Group

AUTHORS:Kerstin Johansson, Karolina Thömkvist, Ingmar Skoog and Sacuiu SF* (*presenter)OBJECTIVE:To determine the effects of electroconvulsive therapy (ECT) in major depression in relation to the development of dementia during long-term follow-up.METHOD:In an observational clinical prospective study of consecutive patients 70 years and older diagnosed with major depression at baseline 2000-2004 (n=1090), who were free of dementia and received antidepressant treatment, with or without ECT, we sought to determine if cognitive decline (mild cognitive impairment and dementia) during 15 -year follow-up was associated with receiving ECT at baseline. The control group was selected among the participants in the Gothenburg H70 Birth Cohort Studies matched by age group and sex 1:1.RESULTS:Among patients with affective syndromes 7% received ECT. During follow-up, 157 patients were diagnosed with dementia, equal proportions among those who received ECT (14.5%) and those who did not receive ECT (14.5%). The relation between ECT and cognitive decline remained non-significant irrespective antidepressive medication or presence of mild cognitive impairment at baseline.CONCLUSION:Preliminary results indicate that ECT was not associated with the development of cognitive decline in the long-term in a hospital-based cohort of 70+ year-olds. The results remain to verify against controls from a representative community sample.

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